CLAIM OF PRIORITY

This application claims priority to U.S. Application No. 63/296,811, filed on January 5, 2022, the contents of which is incorporated herein by reference in its entirety.

BACKGROUND

Alternative splicing is a major source of protein diversity in higher eukaryotes, and is frequently regulated in a tissue-specific or development stage-specific manner. Disease associated alternative splicing patterns in pre-mRNAs are often mapped to changes in splice site signals or sequence motifs and regulatory splicing factors (Faustino and Cooper (2003), Genes Dev 17(4):419-37). Current therapies to modulate RNA expression involve oligonucleotide targeting and gene therapy; however, each of these modalities exhibit unique challenges as currently presented. As such, there is a need for new technologies to modulate RNA expression, including the development of small molecule compounds that target splicing.

SUMMARY

The present disclosure features compounds and related compositions that, inter alia, modulate nucleic acid splicing, e.g., splicing of a pre-mRNA, as well as methods of use thereof. In an embodiment, the compounds described herein are compounds of Formula (I) or (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers thereof. The present disclosure additionally provides methods of using the compounds of the invention (e.g., compounds of Formula (I) or (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers thereof), and compositions thereof, e.g., to target, and in embodiments bind or form a complex with, a nucleic acid (e.g., a pre-mRNA or nucleic acid component of a small nuclear ribonucleoprotein (snRNP) or spliceosome), a protein (e.g., a protein component of an snRNP or spliceosome, e.g., a member of the splicing machinery, e.g., one or more of the Ul, U2, U4, U5, U6, Ul 1, U12, U4atac, U6atac snRNPs), or a combination thereof. In another aspect, the compounds described herein may be used to alter the composition or structure of a nucleic acid (e.g., a pre-mRNA or mRNA (e.g., a pre-mRNA and the mRNA which arises from the pre-mRNA), e.g., by increasing or decreasing splicing at a splice site. In some embodiments, increasing or decreasing splicing results in modulating the level of a gene product (e.g., an RNA or protein) produced. In another aspect, the compounds described herein may be used for the prevention and/or treatment of a disease, disorder, or condition, e.g., a disease, disorder or condition associated with splicing, e.g., alternative splicing. In some embodiments, the compounds described herein (e.g., compounds of Formula (I) or (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers thereof) and compositions thereof are used for the prevention and/or treatment of a proliferative disease, disorder, or condition (e.g., a disease, disorder, or condition characterized by unwanted cell proliferation, e.g., a cancer or a benign neoplasm) in a subject. In some embodiments, the compounds described herein (e.g., compounds of Formula (I) or (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers thereof) and compositions thereof are used for the prevention and/or treatment of a non-proliferative disease, disorder, or condition. In some embodiments, the compounds described herein (e.g., compounds of Formula (I) or (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers thereof) and compositions thereof are used for the prevention and/or treatment of a neurological disease or disorder, an autoimmune disease or disorder, immunodeficiency disease or disorder, a lysosomal storage disease or disorder, a cardiovascular disease or disorder, a metabolic disease or disorder, a respiratory disease or disorder, a renal disease or disorder, or an infectious disease in a subject. In one aspect, the present disclosure provides compounds of Formula (I): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein each of A, B, L ¹ , L ² , X, Y, Z, R ² , R ³ , m, n, and subvariables thereof are defined as described herein. In another aspect, the present disclosure provides compounds of Formula (II): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein each of A, B, L ¹ , L ² , W, Z, R ² , R ³ , m, n, and subvariables thereof are defined as described herein. In another aspect, the present invention provides pharmaceutical compositions comprising a compound of Formulas (I) or (II), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, and optionally a pharmaceutically acceptable excipient. In an embodiment, the pharmaceutical compositions described herein include an effective amount (e.g., a therapeutically effective amount) of a compound of Formulas (I) or (II), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another aspect, the present disclosure provides methods for modulating splicing, e.g., splicing of a nucleic acid (e.g., a DNA or RNA, e.g., a pre-mRNA) with a compound of Formulas (I) or (II), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another aspect, the present disclosure provides compositions for use in modulating splicing, e.g., splicing of a nucleic acid (e.g., a DNA or RNA, e.g., a pre-mRNA) with a compound of Formulas (I) or (II), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. Modulation of splicing may comprise impacting any step involved in splicing and may include an event upstream or downstream of a splicing event. For example, in some embodiments, the compound of Formulas (I) or (II) binds to a target, e.g., a target nucleic acid (e.g., DNA or RNA, e.g., a precursor RNA, e.g., a pre-mRNA), a target protein, or combination thereof (e.g., an snRNP and a pre-mRNA). A target may include a splice site in a pre-mRNA or a component of the splicing machinery, such as the U1 snRNP. In some embodiments, the compound of Formulas (I) or (II) alters a target nucleic acid (e.g., DNA or RNA, e.g., a precursor RNA, e.g., a pre-mRNA), target protein, or combination thereof. In some embodiments, the compound of Formulas (I) or (II) increases or decreases splicing at a splice site on a target nucleic acid (e.g., an RNA, e.g., a precursor RNA, e.g., a pre-mRNA) by about 0.5% or more (e.g., about 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 90%, 95%, or more), relative to a reference (e.g., the absence of a compound of Formulas (I) or (II), e.g., in a healthy or diseased cell or tissue). In some embodiments, the presence of a compound of Formulas (I) or (II) results an increase or decrease of transcription of a target nucleic acid (e.g., an RNA) by about 0.5% or more (e.g., about 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 90%, 95%, or more), relative to a reference (e.g., the absence of a compound of Formulas (I) or (II), e.g., in a healthy or diseased cell or tissue). In another aspect, the present disclosure provides methods for preventing and/or treating a disease, disorder, or condition in a subject by administering a compound of Formulas (I) or (II), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or related compositions. In some embodiments, the disease or disorder entails unwanted or aberrant splicing. In some embodiments, the disease or disorder is a proliferative disease, disorder, or condition. Exemplary proliferative diseases include cancer, a benign neoplasm, or angiogenesis. In other embodiments, the present disclosure provides methods for treating and/or preventing a non-proliferative disease, disorder, or condition. In still other embodiments, the present disclosure provides methods for treating and/or preventing a neurological disease or disorder, autoimmune disease or disorder, immunodeficiency disease or disorder, lysosomal storage disease or disorder, cardiovascular disease or disorder, metabolic disease or disorder, respiratory disease or disorder, renal disease or disorder, or infectious disease. In another aspect, the present disclosure provides methods of down-regulating the expression of (e.g., the level of or the rate of production of) a target protein with a compound of Formulas (I) or (II), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof in a biological sample or subject. In another aspect, the present disclosure provides methods of up-regulating the expression of (e.g., the level of or the rate of production of) a target protein with a compound of Formulas (I) or (II), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof in a biological sample or subject. In another aspect, the present disclosure provides methods of altering the isoform of a target protein with a compound of Formulas (I) or (II), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof in a biological sample or subject. Another aspect of the disclosure relates to methods of inhibiting the activity of a target protein in a biological sample or subject. In some embodiments, administration of a compound of Formulas (I) or (II) to a biological sample, a cell, or a subject comprises inhibition of cell growth or induction of cell death. In another aspect, the present disclosure provides compositions for use in preventing and/or treating a disease, disorder, or condition in a subject by administering a compound of Formulas (I) or (II) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or related compositions. In some embodiments, the disease or disorder entails unwanted or aberrant splicing. In some embodiments, the disease or disorder is a proliferative disease, disorder, or condition. Exemplary proliferative diseases include cancer, a benign neoplasm, or angiogenesis. In other embodiments, the present disclosure provides methods for treating and/or preventing a non-proliferative disease, disorder, or condition. In still other embodiments, the present disclosure provides compositions for use in treating and/or preventing a neurological disease or disorder, autoimmune disease or disorder, immunodeficiency disease or disorder, lysosomal storage disease or disorder, cardiovascular disease or disorder, metabolic disease or disorder, respiratory disease or disorder, renal disease or disorder, or infectious disease. In another aspect, the present disclosure provides compositions for use in down-regulating the expression of (e.g., the level of or the rate of production of) a target protein with a compound of Formulas (I) or (II), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof in a biological sample or subject. In another aspect, the present disclosure provides compositions for use in up-regulating the expression of (e.g., the level of or the rate of production of) a target protein with a compound of Formulas (I) or (II), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof in a biological sample or subject. In another aspect, the present disclosure provides compositions for use in altering the isoform of a target protein with a compound of Formulas (I) or (II), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof in a biological sample or subject. Another aspect of the disclosure relates to compositions for use in inhibiting the activity of a target protein in a biological sample or subject. In some embodiments, administration of a compound of Formulas (I) or (II) to a biological sample, a cell, or a subject comprises inhibition of cell growth or induction of cell death. In another aspect, the present disclosure features kits comprising a container with a compound of Formulas (I) or (II), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer thereof, or a pharmaceutical composition thereof. In certain embodiments, the kits described herein further include instructions for administering the compound of Formulas (I) or (II), or the pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer thereof, or the pharmaceutical composition thereof. In any and all aspects of the present disclosure, in some embodiments, the compound, target nucleic acid (e.g., DNA, RNA, e.g., pre-mRNA), or target protein described herein is a compound, target nucleic acid (e.g., DNA, RNA, e.g., pre-mRNA), or target protein other than a compound, target nucleic acid (e.g., DNA, RNA, e.g., pre-mRNA), or target protein described one of U.S. Patent No.8,729,263, U.S. Publication No.2015/0005289, WO 2014/028459, WO 2016/128343, WO 2016/196386, WO 2017/100726, WO 2018/232039, WO 2018/098446, WO 2019/028440, WO 2019/060917, WO 2019/199972, and WO 2020/004594. In some embodiments, the compound, target nucleic acid (e.g., DNA, RNA, e.g., pre-mRNA), or target protein described herein is a compound, target nucleic acid (e.g., DNA, RNA, e.g., pre-mRNA), or target protein described one of U.S. Patent No.8,729,263, U.S. Publication No. 2015/0005289, WO 2014/028459, WO 2016/128343, WO 2016/196386, WO 2017/100726, WO 2018/232039, WO 2018/098446, WO 2019/028440, WO 2019/060917, WO 2019/199972, and WO 2020/004594, each of which is incorporated herein by reference in its entirety. The details of one or more embodiments of the invention are set forth herein. Other features, objects, and advantages of the invention will be apparent from the Detailed Description, the Examples, and the Claims. DETAILED DESCRIPTION Selected Chemical Definitions Definitions of specific functional groups and chemical terms are described in more detail below. The chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75 ^th Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999; Smith and March, March’s Advanced Organic Chemistry, 5 ^th Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3 ^rd Edition, Cambridge University Press, Cambridge, 1987. The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulae set forth herein are constructed according to the standard rules of chemical valency known in the chemical arts. When a range of values is listed, it is intended to encompass each value and sub–range within the range. For example “C ₁ -C ₆ alkyl” is intended to encompass, C ₁ , C ₂ , C ₃ , C ₄ , C ₅ , C ₆ , C ₁ -C ₆ , C ₁ -C ₅ , C ₁ -C ₄ , C ₁ -C ₃ , C ₁ -C ₂ , C ₂ -C ₆ , C ₂ -C ₅ , C ₂ -C ₄ , C ₂ -C ₃ , C ₃ -C ₆ , C ₃ -C ₅ , C ₃ -C ₄ , C ₄ -C ₆ , C ₄ -C ₅ , and C ₅ -C ₆ alkyl. The following terms are intended to have the meanings presented therewith below and are useful in understanding the description and intended scope of the present invention. As used herein, “alkyl” refers to a radical of a straight–chain or branched saturated hydrocarbon group having from 1 to 24 carbon atoms (“C ₁ -C ₂₄ alkyl”). In some embodiments, an alkyl group has 1 to 12 carbon atoms (“C ₁ -C ₁₂ alkyl”). In some embodiments, an alkyl group has 1 to 8 carbon atoms (“C ₁ -C ₈ alkyl”). In some embodiments, an alkyl group has 1 to 6 carbon atoms (“C ₁ -C ₆ alkyl”). In some embodiments, an alkyl group has 2 to 6 carbon atoms (“ C ₂ -C ₆ alkyl”). In some embodiments, an alkyl group has 1 carbon atom (“C ₁ alkyl”). Examples of C ₁ - C ₆ alkyl groups include methyl (C ₁ ), ethyl (C ₂ ), n–propyl (C ₃ ), isopropyl (C ₃ ), n–butyl (C ₄ ), tert– butyl (C ₄ ), sec–butyl (C ₄ ), iso–butyl (C ₄ ), n–pentyl (C ₅ ), 3–pentanyl (C ₅ ), amyl (C ₅ ), neopentyl (C ₅ ), 3–methyl–2–butanyl (C ₅ ), tertiary amyl (C ₅ ), and n–hexyl (C ₆ ). Additional examples of alkyl groups include n–heptyl (C ₇ ), n–octyl (C ₈ ) and the like. Each instance of an alkyl group may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted alkyl”) or substituted (a “substituted alkyl”) with one or more substituents; e.g., for instance from 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. In certain embodiments, the alkyl group is unsubstituted C _1– C ₁₀ alkyl (e.g., –CH ₃ ). In certain embodiments, the alkyl group is substituted C ₁ –C ₆ alkyl. As used herein, “alkenyl” refers to a radical of a straight–chain or branched hydrocarbon group having from 2 to 24 carbon atoms, one or more carbon–carbon double bonds, and no triple bonds (“C ₂ -C ₂₄ alkenyl”). In some embodiments, an alkenyl group has 2 to 10 carbon atoms (“C ₂ -C ₁₀ alkenyl”). In some embodiments, an alkenyl group has 2 to 8 carbon atoms (“C ₂ -C ₈ alkenyl”). In some embodiments, an alkenyl group has 2 to 6 carbon atoms (“C ₂ -C ₆ alkenyl”). In some embodiments, an alkenyl group has 2 carbon atoms (“C ₂ alkenyl”). The one or more carbon–carbon double bonds can be internal (such as in 2–butenyl) or terminal (such as in 1– butenyl). Examples of C ₂ -C ₄ alkenyl groups include ethenyl (C ₂ ), 1–propenyl (C ₃ ), 2–propenyl (C ₃ ), 1–butenyl (C ₄ ), 2–butenyl (C ₄ ), butadienyl (C ₄ ), and the like. Examples of C ₂ -C ₆ alkenyl groups include the aforementioned C ₂ –4 alkenyl groups as well as pentenyl (C ₅ ), pentadienyl (C ₅ ), hexenyl (C ₆ ), and the like. Additional examples of alkenyl include heptenyl (C7), octenyl (C ₈ ), octatrienyl (C ₈ ), and the like. Each instance of an alkenyl group may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted alkenyl ) or substituted (a “substituted alkenyl”) with one or more substituents e.g., for instance from 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. In certain embodiments, the alkenyl group is unsubstituted C ₁ – C ₁₀ alkenyl. In certain embodiments, the alkenyl group is substituted C _2– C ₆ alkenyl. As used herein, the term “alkynyl” refers to a radical of a straight–chain or branched hydrocarbon group having from 2 to 24 carbon atoms, one or more carbon–carbon triple bonds (“C ₂ -C ₂₄ alkenyl”). In some embodiments, an alkynyl group has 2 to 10 carbon atoms (“C ₂ -C ₁₀ alkynyl”). In some embodiments, an alkynyl group has 2 to 8 carbon atoms (“C ₂ -C ₈ alkynyl”). In some embodiments, an alkynyl group has 2 to 6 carbon atoms (“C ₂ -C ₆ alkynyl”). In some embodiments, an alkynyl group has 2 carbon atoms (“C ₂ alkynyl”). The one or more carbon– carbon triple bonds can be internal (such as in 2–butynyl) or terminal (such as in 1–butynyl). Examples of C ₂ -C ₄ alkynyl groups include ethynyl (C ₂ ), 1–propynyl (C ₃ ), 2–propynyl (C ₃ ), 1– butynyl (C ₄ ), 2–butynyl (C ₄ ), and the like. Each instance of an alkynyl group may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted alkynyl”) or substituted (a “substituted alkynyl”) with one or more substituents e.g., for instance from 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. In certain embodiments, the alkynyl group is unsubstituted C _2–10 alkynyl. In certain embodiments, the alkynyl group is substituted C _2–6 alkynyl. As used herein, the term "haloalkyl," refers to a non-cyclic stable straight or branched chain, or combinations thereof, including at least one carbon atom and at least one halogen selected from the group consisting of F, Cl, Br, and I. The halogen(s) F, Cl, Br, and I may be placed at any position of the haloalkyl group. Exemplary haloalkyl groups include, but are not limited to: -CF ₃ , -CCl ₃ , -CH ₂ -CF ₃ , -CH ₂ -CCl ₃ , -CH ₂ -CBr ₃ , -CH ₂ -Cl ₃ , -CH ₂ -CH ₂ -CH(CF ₃ )-CH ₃ , - CH ₂ -CH ₂ -CH(Br)-CH ₃ , and -CH ₂ -CH=CH-CH ₂ -CF ₃ . Each instance of a haloalkyl group may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted haloalkyl”) or substituted (a “substituted haloalkyl”) with one or more substituents e.g., for instance from 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. As used herein, the term "heteroalkyl," refers to a non-cyclic stable straight or branched chain, or combinations thereof, including at least one carbon atom and at least one heteroatom selected from the group consisting of O, N, P, Si, and S, and wherein the nitrogen and sulfur atoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized. The heteroatom(s) O, N, P, S, and Si may be placed at any position of the heteroalkyl group. Exemplary heteroalkyl groups include, but are not limited to: -CH ₂ -CH ₂ -O-CH ₃ , -CH ₂ -CH ₂ -NH- CH ₃ , -CH ₂ -CH ₂ -N(CH ₃ )-CH ₃ , -CH ₂ -S-CH ₂ -CH ₃ , -CH ₂ -CH ₂ , -S(O)-CH ₃ , -CH ₂ -CH ₂ -S(O) ₂ -CH ₃ , - CH=CH-O-CH ₃ , -Si(CH ₃ ) ₃ , -CH ₂ -CH=N-OCH ₃ , -CH=CH-N(CH ₃ )-CH ₃ , -O-CH ₃ , and -O-CH ₂ - CH ₃ . Up to two or three heteroatoms may be consecutive, such as, for example, -CH ₂ -NH-OCH ₃ and -CH ₂ -O-Si(CH ₃ ) ₃ . Where "heteroalkyl" is recited, followed by recitations of specific heteroalkyl groups, such as –CH ₂ O, –NR ^C R ^D , or the like, it will be understood that the terms heteroalkyl and –CH ₂ O or –NR ^C R ^D are not redundant or mutually exclusive. Rather, the specific heteroalkyl groups are recited to add clarity. Thus, the term "heteroalkyl" should not be interpreted herein as excluding specific heteroalkyl groups, such as –CH ₂ O, –NR ^C R ^D , or the like. Each instance of a heteroalkyl group may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted heteroalkyl”) or substituted (a “substituted heteroalkyl”) with one or more substituents e.g., for instance from 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. As used herein, “aryl” refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 π electrons shared in a cyclic array) having 6–14 ring carbon atoms and zero heteroatoms provided in the aromatic ring system (“C ₆ -C ₁₄ aryl”). In some embodiments, an aryl group has six ring carbon atoms (“C ₆ aryl”; e.g., phenyl). In some embodiments, an aryl group has ten ring carbon atoms (“C ₁₀ aryl”; e.g., naphthyl such as 1–naphthyl and 2–naphthyl). In some embodiments, an aryl group has fourteen ring carbon atoms (“C ₁₄ aryl”; e.g., anthracyl). An aryl group may be described as, e.g., a C ₆ -C ₁₀ -membered aryl, wherein the term “membered” refers to the non-hydrogen ring atoms within the moiety. Aryl groups include phenyl, naphthyl, indenyl, and tetrahydronaphthyl. Each instance of an aryl group may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted aryl”) or substituted (a “substituted aryl”) with one or more substituents. In certain embodiments, the aryl group is unsubstituted C ₆ -C ₁₄ aryl. In certain embodiments, the aryl group is substituted C ₆ -C ₁₄ aryl. As used herein, “heteroaryl” refers to a radical of a 5–10 membered monocyclic or bicyclic 4n+2 aromatic ring system (e.g., having 6 or 10 π electrons shared in a cyclic array) having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen and sulfur (“5–10 membered heteroaryl”). In heteroaryl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. Heteroaryl bicyclic ring systems can include one or more heteroatoms in one or both rings. “Heteroaryl” also includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more aryl groups wherein the point of attachment is either on the aryl or heteroaryl ring, and in such instances, the number of ring members designates the number of ring members in the fused (aryl/heteroaryl) ring system. Bicyclic heteroaryl groups wherein one ring does not contain a heteroatom (e.g., indolyl, quinolinyl, carbazolyl, and the like) the point of attachment can be on either ring, i.e., either the ring bearing a heteroatom (e.g., 2–indolyl) or the ring that does not contain a heteroatom (e.g., 5–indolyl). A heteroaryl group may be described as, e.g., a 6-10-membered heteroaryl, wherein the term “membered” refers to the non-hydrogen ring atoms within the moiety. Each instance of a heteroaryl group may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted heteroaryl”) or substituted (a “substituted heteroaryl”) with one or more substituents e.g., for instance from 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. Exemplary 5–membered heteroaryl groups containing one heteroatom include, without limitation, pyrrolyl, furanyl and thiophenyl. Exemplary 5–membered heteroaryl groups containing two heteroatoms include, without limitation, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5–membered heteroaryl groups containing three heteroatoms include, without limitation, triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5–membered heteroaryl groups containing four heteroatoms include, without limitation, tetrazolyl. Exemplary 6–membered heteroaryl groups containing one heteroatom include, without limitation, pyridinyl. Exemplary 6–membered heteroaryl groups containing two heteroatoms include, without limitation, pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6– membered heteroaryl groups containing three or four heteroatoms include, without limitation, triazinyl and tetrazinyl, respectively. Exemplary 7–membered heteroaryl groups containing one heteroatom include, without limitation, azepinyl, oxepinyl, and thiepinyl. Exemplary 5,6– bicyclic heteroaryl groups include, without limitation, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzthiazolyl, benzisothiazolyl, benzthiadiazolyl, indolizinyl, and purinyl. Exemplary 6,6–bicyclic heteroaryl groups include, without limitation, naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl. Other exemplary heteroaryl groups include heme and heme derivatives. As used herein, “cycloalkyl” refers to a radical of a non–aromatic cyclic hydrocarbon group having from 3 to 10 ring carbon atoms (“C ₃ -C ₁₀ cycloalkyl”) and zero heteroatoms in the non–aromatic ring system. In some embodiments, a cycloalkyl group has 3 to 8 ring carbon atoms (“C ₃ -C ₈ cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms (“C ₃ -C ₆ cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms (“C ₃ -C ₆ cycloalkyl”). In some embodiments, a cycloalkyl group has 5 to 10 ring carbon atoms (“C ₅ -C ₁₀ cycloalkyl”). A cycloalkyl group may be described as, e.g., a C ₄ -C ₇ -membered cycloalkyl, wherein the term “membered” refers to the non-hydrogen ring atoms within the moiety. Exemplary C ₃ -C ₆ cycloalkyl groups include, without limitation, cyclopropyl (C ₃ ), cyclopropenyl (C ₃ ), cyclobutyl (C ₄ ), cyclobutenyl (C ₄ ), cyclopentyl (C ₅ ), cyclopentenyl (C ₅ ), cyclohexyl (C ₆ ), cyclohexenyl (C ₆ ), cyclohexadienyl (C ₆ ), and the like. Exemplary C ₃ -C ₈ cycloalkyl groups include, without limitation, the aforementioned C ₃ -C ₆ cycloalkyl groups as well as cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C ₈ ), cyclooctenyl (C ₈ ), cubanyl (C ₈ ), bicyclo[1.1.1]pentanyl (C ₅ ), bicyclo[2.2.2]octanyl (C ₈ ), bicyclo[2.1.1]hexanyl (C ₆ ), bicyclo[3.1.1]heptanyl (C ₇ ), and the like. Exemplary C ₃ -C ₁₀ cycloalkyl groups include, without limitation, the aforementioned C ₃ -C ₈ cycloalkyl groups as well as cyclononyl (C ₉ ), cyclononenyl (C ₉ ), cyclodecyl (C ₁₀ ), cyclodecenyl (C ₁₀ ), octahydro–1H–indenyl (C ₉ ), decahydronaphthalenyl (C ₁₀ ), spiro[4.5]decanyl (C ₁₀ ), and the like. As the foregoing examples illustrate, in certain embodiments, the cycloalkyl group is either monocyclic (“monocyclic cycloalkyl”) or contain a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic cycloalkyl”) and can be saturated or can be partially unsaturated. “Cycloalkyl” also includes ring systems wherein the cycloalkyl ring, as defined above, is fused with one or more aryl groups wherein the point of attachment is on the cycloalkyl ring, and in such instances, the number of carbons continue to designate the number of carbons in the cycloalkyl ring system. Each instance of a cycloalkyl group may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted cycloalkyl”) or substituted (a “substituted cycloalkyl”) with one or more substituents. In certain embodiments, the cycloalkyl group is unsubstituted C ₃ -C ₁₀ cycloalkyl. In certain embodiments, the cycloalkyl group is a substituted C ₃ -C ₁₀ cycloalkyl. “Heterocyclyl” as used herein refers to a radical of a 3– to 16–membered non–aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon (“3–16 membered heterocyclyl”). In heterocyclyl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. A heterocyclyl group can either be monocyclic (“monocyclic heterocyclyl”) or a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic heterocyclyl”), and can be saturated or can be partially unsaturated. Heterocyclyl bicyclic ring systems can include one or more heteroatoms in one or both rings. “Heterocyclyl” also includes ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more cycloalkyl groups wherein the point of attachment is either on the cycloalkyl or heterocyclyl ring, or ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups, wherein the point of attachment is on the heterocyclyl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heterocyclyl ring system. A heterocyclyl group may be described as, e.g., a 3-7-membered heterocyclyl, wherein the term “membered” refers to the non- hydrogen ring atoms, i.e., carbon, nitrogen, oxygen, sulfur, boron, phosphorus, and silicon, within the moiety. Each instance of heterocyclyl may be independently optionally substituted, i.e., unsubstituted (an “unsubstituted heterocyclyl”) or substituted (a “substituted heterocyclyl”) with one or more substituents. In certain embodiments, the heterocyclyl group is unsubstituted 3–16 membered heterocyclyl. In certain embodiments, the heterocyclyl group is substituted 3– 16 membered heterocyclyl. Exemplary 3–membered heterocyclyl groups containing one heteroatom include, without limitation, azirdinyl, oxiranyl, thiorenyl. Exemplary 4–membered heterocyclyl groups containing one heteroatom include, without limitation, azetidinyl, oxetanyl and thietanyl. Exemplary 5–membered heterocyclyl groups containing one heteroatom include, without limitation, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl and pyrrolyl–2,5–dione. Exemplary 5–membered heterocyclyl groups containing two heteroatoms include, without limitation, dioxolanyl, oxasulfuranyl, disulfuranyl, and oxazolidin–2–one. Exemplary 5–membered heterocyclyl groups containing three heteroatoms include, without limitation, triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6–membered heterocyclyl groups containing one heteroatom include, without limitation, piperidinyl (e.g., 2,2,6,6-tetramethylpiperidinyl), tetrahydropyranyl, dihydropyridinyl, pyridinonyl (e.g., 1-methylpyridin2-onyl), and thianyl. Exemplary 6–membered heterocyclyl groups containing two heteroatoms include, without limitation, piperazinyl, morpholinyl, pyridazinonyl (2-methylpyridazin-3-onyl), pyrimidinonyl (e.g., 1-methylpyrimidin-2-onyl, 3- methylpyrimidin-4-onyl), dithianyl, dioxanyl. Exemplary 6–membered heterocyclyl groups containing two heteroatoms include, without limitation, triazinanyl. Exemplary 7–membered heterocyclyl groups containing one heteroatom include, without limitation, azepanyl, oxepanyl and thiepanyl. Exemplary 8–membered heterocyclyl groups containing one heteroatom include, without limitation, azocanyl, oxecanyl and thiocanyl. Exemplary 5–membered heterocyclyl groups fused to a C ₆ aryl ring (also referred to herein as a 5,6–bicyclic heterocyclyl ring) include, without limitation, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, benzoxazolinonyl, and the like. Exemplary 5–membered heterocyclyl groups fused to a heterocyclyl ring (also referred to herein as a 5,5–bicyclic heterocyclyl ring) include, without limitation, octahydropyrrolopyrrolyl (e.g., octahydropyrrolo[3,4-c]pyrrolyl), and the like. Exemplary 6-membered heterocyclyl groups fused to a heterocyclyl ring (also referred to as a 4,6-membered heterocyclyl ring) include, without limitation, diazaspirononanyl (e.g., 2,7- diazaspiro[3.5]nonanyl). Exemplary 6–membered heterocyclyl groups fused to an aryl ring (also referred to herein as a 6,6–bicyclic heterocyclyl ring) include, without limitation, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and the like. Exemplary 6–membered heterocyclyl groups fused to a cycloalkyl ring (also referred to herein as a 6,7-bicyclic heterocyclyl ring) include, without limitation, azabicyclooctanyl (e.g., (1,5)-8-azabicyclo[3.2.1]octanyl). Exemplary 6–membered heterocyclyl groups fused to a cycloalkyl ring (also referred to herein as a 6,8-bicyclic heterocyclyl ring) include, without limitation, azabicyclononanyl (e.g., 9- azabicyclo[3.3.1]nonanyl). The terms "alkylene," “alkenylene,” “alkynylene,” “haloalkylene,” “heteroalkylene,” “cycloalkylene,” or “heterocyclylene,” alone or as part of another substituent, mean, unless otherwise stated, a divalent radical derived from an alkyl, alkenyl, alkynyl, haloalkylene, heteroalkylene, cycloalkyl, or heterocyclyl respectively. For example, the term "alkenylene," by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from an alkene. An alkylene, alkenylene, alkynylene, haloalkylene, heteroalkylene, cycloalkylene, or heterocyclylene group may be described as, e.g., a C ₁ -C ₆ -membered alkylene, C ₂ -C ₆ -membered alkenylene, C ₂ -C ₆ -membered alkynylene, C ₁ -C ₆ -membered haloalkylene, C ₁ - C ₆ -membered heteroalkylene, C ₃ -C ₈ -membered cycloalkylene, or C ₃ -C ₈ -membered heterocyclylene, wherein the term “membered” refers to the non-hydrogen atoms within the moiety. In the case of heteroalkylene and heterocyclylene groups, heteroatoms can also occupy either or both of the chain termini (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, and the like). Still further, no orientation of the linking group is implied by the direction in which the formula of the linking group is written. For example, the formula - C(O) ₂ R’- may represent both -C(O) ₂ R’- and –R’C(O) ₂ -. As used herein, the terms “cyano” or “–CN” refer to a substituent having a carbon atom joined to a nitrogen atom by a triple bond, e.g., C≡N. As used herein, the terms “halogen” or “halo” refer to fluorine, chlorine, bromine or iodine. As used herein, the term “hydroxy” refers to –OH. As used herein, the term “nitro” refers to a substitutent having two oxygen atoms bound to a nitrogen atom, e.g., -NO ₂ . As used herein, the term “nucleobase” as used herein, is a nitrogen-containing biological compounds found linked to a sugar within a nucleoside—the basic building blocks of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). The primary, or naturally occurring, nucleobases are cytosine (DNA and RNA), guanine (DNA and RNA), adenine (DNA and RNA), thymine (DNA) and uracil (RNA), abbreviated as C, G, A, T, and U, respectively. Because A, G, C, and T appear in the DNA, these molecules are called DNA-bases; A, G, C, and U are called RNA-bases. Adenine and guanine belong to the double-ringed class of molecules called purines (abbreviated as R). Cytosine, thymine, and uracil are all pyrimidines. Other nucleobases that do not function as normal parts of the genetic code, are termed non-naturally occurring. In an embodiment, a nucleobase may be chemically modified, for example, with an alkyl (e.g., methyl), halo, -O-alkyl, or other modification. As used herein, the term “nucleic acid” refers to deoxyribonucleic acids (DNA) or ribonucleic acids (RNA) and polymers thereof in either single- or double-stranded form. The term “nucleic acid” includes a gene, cDNA, pre-mRNA, or an mRNA. In one embodiment, the nucleic acid molecule is synthetic (e.g., chemically synthesized) or recombinant. Unless specifically limited, the term encompasses nucleic acids containing analogues or derivatives of natural nucleotides that have similar binding properties as the reference nucleic acid and are metabolized in a manner similar to naturally occurring nucleotides. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions), alleles, orthologs, SNPs, and complementarity sequences as well as the sequence explicitly indicated. As used herein, “oxo” refers to a carbonyl, i.e., -C(O)-. The symbol “ ” as used herein in relation to a compound of Formula (I) or (II) refers to an attachment point to another moiety or functional group within the compound. Alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups, as defined herein, are optionally substituted. In general, the term “substituted”, whether preceded by the term “optionally” or not, means that at least one hydrogen present on a group (e.g., a carbon or nitrogen atom) is replaced with a permissible substituent, e.g., a substituent which upon substitution results in a stable compound, e.g., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction. Unless otherwise indicated, a “substituted” group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituent is either the same or different at each position. The term “substituted” is contemplated to include substitution with all permissible substituents of organic compounds, such as any of the substituents described herein that result in the formation of a stable compound. The present disclosure contemplates any and all such combinations in order to arrive at a stable compound. For purposes of this invention, heteroatoms such as nitrogen may have hydrogen substituents and/or any suitable substituent as described herein which satisfy the valencies of the heteroatoms and results in the formation of a stable moiety. Two or more substituents may optionally be joined to form aryl, heteroaryl, cycloalkyl, or heterocyclyl groups. Such so-called ring-forming substituents are typically, though not necessarily, found attached to a cyclic base structure. In one embodiment, the ring-forming substituents are attached to adjacent members of the base structure. For example, two ring- forming substituents attached to adjacent members of a cyclic base structure create a fused ring structure. In another embodiment, the ring-forming substituents are attached to a single member of the base structure. For example, two ring-forming substituents attached to a single member of a cyclic base structure create a spirocyclic structure. In yet another embodiment, the ring- forming substituents are attached to non-adjacent members of the base structure. The compounds provided herein may exist in one or more particular geometric, optical, enantiomeric, diasteriomeric, epimeric, stereoisomeric, tautomeric, conformational, or anomeric forms, including but not limited to: cis- and trans-forms; E- and Z-forms; endo- and exo-forms; R-, S-, and meso-forms; D- and L-forms; d- and l-forms; (+) and (-) forms; keto-, enol-, and enolate-forms; syn- and anti-forms; synclinal- and anticlinal-forms; α- and β-forms; axial and equatorial forms; boat-, chair-, twist-, envelope-, and half chair-forms; and combinations thereof, hereinafter collectively referred to as "isomers" (or "isomeric forms"). Compounds described herein can comprise one or more asymmetric centers, and thus can exist in various isomeric forms, e.g., enantiomers and/or diastereomers. For example, the compounds described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. In an embodiment, the stereochemistry depicted in a compound is relative rather than absolute. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high-pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric syntheses. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, Stereochemistry of Carbon Compounds (McGraw–Hill, NY, 1962); and Wilen, Tables of Resolving Agents and Optical Resolutions p.268 (E.L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972). This disclosure additionally encompasses compounds described herein as individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers. As used herein, a pure enantiomeric compound is substantially free from other enantiomers or stereoisomers of the compound (i.e., in enantiomeric excess). In other words, an “S” form of the compound is substantially free from the “R” form of the compound and is, thus, in enantiomeric excess of the “R” form. The term “enantiomerically pure” or “pure enantiomer” denotes that the compound comprises more than 75% by weight, more than 80% by weight, more than 85% by weight, more than 90% by weight, more than 91% by weight, more than 92% by weight, more than 93% by weight, more than 94% by weight, more than 95% by weight, more than 96% by weight, more than 97% by weight, more than 98% by weight, more than 99% by weight, more than 99.5% by weight, or more than 99.9% by weight, of the enantiomer. In certain embodiments, the weights are based upon total weight of all enantiomers or stereoisomers of the compound. In the compositions provided herein, an enantiomerically pure compound can be present with other active or inactive ingredients. For example, a pharmaceutical composition comprising an enantiomerically pure R–compound can comprise, for example, about 90% excipient and about 10% enantiomerically pure R–compound. In certain embodiments, the enantiomerically pure R–compound in such compositions can, for example, comprise, at least about 95% by weight R–compound and at most about 5% by weight S–compound, by total weight of the compound. For example, a pharmaceutical composition comprising an enantiomerically pure S– compound can comprise, for example, about 90% excipient and about 10% enantiomerically pure S–compound. In certain embodiments, the enantiomerically pure S–compound in such compositions can, for example, comprise, at least about 95% by weight S–compound and at most about 5% by weight R–compound, by total weight of the compound. In some embodiments, a diastereomerically pure compound can be present with other active or inactive ingredients. For example, a pharmaceutical composition comprising a diastereometerically pure exo compound can comprise, for example, about 90% excipient and about 10% diastereometerically pure exo compound. In certain embodiments, the diastereometerically pure exo compound in such compositions can, for example, comprise, at least about 95% by weight exo compound and at most about 5% by weight endo compound, by total weight of the compound. For example, a pharmaceutical composition comprising a diastereometerically pure endo compound can comprise, for example, about 90% excipient and about 10% diastereometerically pure endo compound. In certain embodiments, the diastereometerically pure endo compound in such compositions can, for example, comprise, at least about 95% by weight endo compound and at most about 5% by weight exo compound, by total weight of the compound. In some embodiments, an isomerically pure compound can be present with other active or inactive ingredients. For example, a pharmaceutical composition comprising a isomerically pure exo compound can comprise, for example, about 90% excipient and about 10% isomerically pure exo compound. In certain embodiments, the isomerically pure exo compound in such compositions can, for example, comprise, at least about 95% by weight exo compound and at most about 5% by weight endo compound, by total weight of the compound. For example, a pharmaceutical composition comprising an isomerically pure endo compound can comprise, for example, about 90% excipient and about 10% isomerically pure endo compound. In certain embodiments, the isomerically pure endo compound in such compositions can, for example, comprise, at least about 95% by weight endo compound and at most about 5% by weight exo compound, by total weight of the compound. In certain embodiments, the active ingredient can be formulated with little or no excipient or carrier. Compound described herein may also comprise one or more isotopic substitutions. For example, H may be in any isotopic form, including ¹ H, ² H (D or deuterium), and ³ H (T or tritium); C may be in any isotopic form, including ¹² C, ¹³ C, and ¹⁴ C; O may be in any isotopic form, including ¹⁶ O and ¹⁸ O; N may be in any isotopic form, including ¹⁴ N and ¹⁵ N; F may be in any isotopic form, including ¹⁸ F, ¹⁹ F, and the like. The term "pharmaceutically acceptable salt" is meant to include salts of the active compounds that are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein. When compounds of the present disclosure contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salt, or a similar salt. When compounds of the present invention contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids and the like, as well as the salts derived from organic acids like acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, methanesulfonic, and the like. Also included are salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galactunoric acids and the like (see, e.g., Berge et al, Journal of Pharmaceutical Science 66: 1-19 (1977)). Certain specific compounds of the present invention contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts. These salts may be prepared by methods known to those skilled in the art. Other pharmaceutically acceptable carriers known to those of skill in the art are suitable for the present invention. In addition to salt forms, the present disclosure provides compounds in a prodrug form. Prodrugs of the compounds described herein are those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the present invention. Additionally, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex vivo environment. For example, prodrugs can be slowly converted to the compounds of the present invention when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent. The term “solvate” refers to forms of the compound that are associated with a solvent, usually by a solvolysis reaction. This physical association may include hydrogen bonding. Conventional solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, and the like. The compounds of Formulas (I) or (II) may be prepared, e.g., in crystalline form, and may be solvated. Suitable solvates include pharmaceutically acceptable solvates and further include both stoichiometric solvates and non-stoichiometric solvates. In certain instances, the solvate will be capable of isolation, for example, when one or more solvent molecules are incorporated in the crystal lattice of a crystalline solid. “Solvate” encompasses both solution-phase and isolable solvates. Representative solvates include hydrates, ethanolates, and methanolates. The term “hydrate” refers to a compound which is associated with water. Typically, the number of the water molecules contained in a hydrate of a compound is in a definite ratio to the number of the compound molecules in the hydrate. Therefore, a hydrate of a compound may be represented, for example, by the general formula R ^x H ₂ O, wherein R is the compound and wherein x is a number greater than 0. A given compound may form more than one type of hydrates, including, e.g., monohydrates (x is 1), lower hydrates (x is a number greater than 0 and smaller than 1, e.g., hemihydrates (R ^0.5 H ₂ O)), and polyhydrates (x is a number greater than 1, e.g., dihydrates (R ^2 H ₂ O) and hexahydrates (R ^6 H ₂ O)). The term “tautomer” refers to compounds that are interchangeable forms of a particular compound structure, and that vary in the displacement of hydrogen atoms and electrons. Thus, two structures may be in equilibrium through the movement of π electrons and an atom (usually H). For example, enols and ketones are tautomers because they are rapidly interconverted by treatment with either acid or base. Another example of tautomerism is the aci- and nitro- forms of phenylnitromethane that are likewise formed by treatment with acid or base. Tautomeric forms may be relevant to the attainment of the optimal chemical reactivity and biological activity of a compound of interest. Other Definitions The following definitions are more general terms used throughout the present disclosure. The articles “a” and “an” refer to one or more than one (e.g., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element. The term “and/or” means either “and” or “or” unless indicated otherwise. The term “about” is used herein to mean within the typical ranges of tolerances in the art. For example, “about” can be understood as about 2 standard deviations from the mean. In certain embodiments, about means +10%. In certain embodiments, about means +5%. When about is present before a series of numbers or a range, it is understood that “about” can modify each of the numbers in the series or range. “Acquire” or “acquiring” as used herein, refer to obtaining possession of a value, e.g., a numerical value, or image, or a physical entity (e.g., a sample), by “directly acquiring” or “indirectly acquiring” the value or physical entity. “Directly acquiring” means performing a process (e.g., performing an analytical method or protocol) to obtain the value or physical entity. “Indirectly acquiring” refers to receiving the value or physical entity from another party or source (e.g., a third-party laboratory that directly acquired the physical entity or value). Directly acquiring a value or physical entity includes performing a process that includes a physical change in a physical substance or the use of a machine or device. Examples of directly acquiring a value include obtaining a sample from a human subject. Directly acquiring a value includes performing a process that uses a machine or device, e.g., mass spectrometer to acquire mass spectrometry data. The terms “administer,” “administering,” or “administration,” as used herein refers to implanting, absorbing, ingesting, injecting, inhaling, or otherwise introducing an inventive compound, or a pharmaceutical composition thereof. As used herein, the terms “condition,” “disease,” and “disorder” are used interchangeably. An “effective amount” of a compound of Formulas (I) or (II) refers to an amount sufficient to elicit the desired biological response, i.e., treating the condition. As will be appreciated by those of ordinary skill in this art, the effective amount of a compound of Formulas (I) or (II) may vary depending on such factors as the desired biological endpoint, the pharmacokinetics of the compound, the condition being treated, the mode of administration, and the age and health of the subject. An effective amount encompasses therapeutic and prophylactic treatment. For example, in treating cancer, an effective amount of an inventive compound may reduce the tumor burden or stop the growth or spread of a tumor. A “therapeutically effective amount” of a compound of Formulas (I) or (II) is an amount sufficient to provide a therapeutic benefit in the treatment of a condition or to delay or minimize one or more symptoms associated with the condition. In some embodiments, a therapeutically effective amount is an amount sufficient to provide a therapeutic benefit in the treatment of a condition or to minimize one or more symptoms associated with the condition. A therapeutically effective amount of a compound means an amount of therapeutic agent, alone or in combination with other therapies, which provides a therapeutic benefit in the treatment of the condition. The term “therapeutically effective amount” can encompass an amount that improves overall therapy, reduces or avoids symptoms or causes of the condition, or enhances the therapeutic efficacy of another therapeutic agent. The terms “peptide,” “polypeptide,” and “protein” are used interchangeably, and refer to a compound comprised of amino acid residues covalently linked by peptide bonds. A protein or peptide must contain at least two amino acids, and no limitation is placed on the maximum number of amino acids that can comprised therein. Polypeptides include any peptide or protein comprising two or more amino acids joined to each other by peptide bonds. As used herein, the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types. “Prevention,” “prevent,” and “preventing” as used herein refers to a treatment that comprises administering a therapy, e.g., administering a compound described herein (e.g., a compound of Formulas (I) or (II)) prior to the onset of a disease, disorder, or condition in order to preclude the physical manifestation of said disease, disorder, or condition. In some embodiments, “prevention,” “prevent,” and “preventing” require that signs or symptoms of the disease, disorder, or condition have not yet developed or have not yet been observed. In some embodiments, treatment comprises prevention and in other embodiments it does not. A “subject” to which administration is contemplated includes, but is not limited to, humans (i.e., a male or female of any age group, e.g., a pediatric subject (e.g., infant, child, adolescent) or adult subject (e.g., young adult, middle–aged adult, or senior adult)) and/or other non–human animals, for example, mammals (e.g., primates (e.g., cynomolgus monkeys, rhesus monkeys); commercially relevant mammals such as cattle, pigs, horses, sheep, goats, cats, and/or dogs) and birds (e.g., commercially relevant birds such as chickens, ducks, geese, and/or turkeys). In certain embodiments, the animal is a mammal. The animal may be a male or female and at any stage of development. A non–human animal may be a transgenic animal. As used herein, the terms “treatment,” “treat,” and “treating” refer to reversing, alleviating, delaying the onset of, or inhibiting the progress of one or more of a symptom, manifestation, or underlying cause of a disease, disorder, or condition (e.g., as described herein), e.g., by administering a therapy, e.g., administering a compound described herein (e.g., a compound of Formulas (I) or (II)). In an embodiment, treating comprises reducing, reversing, alleviating, delaying the onset of, or inhibiting the progress of a symptom of a disease, disorder, or condition. In an embodiment, treating comprises reducing, reversing, alleviating, delaying the onset of, or inhibiting the progress of a manifestation of a disease, disorder, or condition. In an embodiment, treating comprises reducing, reversing, alleviating, reducing, or delaying the onset of, an underlying cause of a disease, disorder, or condition. In some embodiments, “treatment,” “treat,” and “treating” require that signs or symptoms of the disease, disorder, or condition have developed or have been observed. In other embodiments, treatment may be administered in the absence of signs or symptoms of the disease or condition, e.g., in preventive treatment. For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., in light of a history of symptoms and/or in light of genetic or other susceptibility factors). Treatment may also be continued after symptoms have resolved, for example, to delay or prevent recurrence. Treatment may also be continued after symptoms have resolved, for example, to delay or prevent recurrence. In some embodiments, treatment comprises prevention and in other embodiments it does not. A “proliferative disease” refers to a disease that occurs due to abnormal extension by the multiplication of cells (Walker, Cambridge Dictionary of Biology; Cambridge University Press: Cambridge, UK, 1990). A proliferative disease may be associated with: 1) the pathological proliferation of normally quiescent cells; 2) the pathological migration of cells from their normal location (e.g., metastasis of neoplastic cells); 3) the pathological expression of proteolytic enzymes such as the matrix metalloproteinases (e.g., collagenases, gelatinases, and elastases); 4) the pathological angiogenesis as in proliferative retinopathy and tumor metastasis; or 5) evasion of host immune surveillance and elimination of neoplastic cells. Exemplary proliferative diseases include cancers (i.e., “malignant neoplasms”), benign neoplasms, and angiogenesis. A “non-proliferative disease” refers to a disease that does not primarily extend through the abnormal multiplication of cells. A non-proliferative disease may be associated with any cell type or tissue type in a subject. Exemplary non-proliferative diseases include neurological diseases or disorders (e.g., a repeat expansion disease); autoimmune disease or disorders; immunodeficiency diseases or disorders; lysosomal storage diseases or disorders; inflammatory diseases or disorders; cardiovascular conditions, diseases, or disorders; metabolic diseases or disorders; respiratory conditions, diseases, or disorders; renal diseases or disorders; and infectious diseases. Compounds In one aspect, the present disclosure features a compound of Formula (I): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; L ¹ and L ² are each independently absent, C ₁ -C ₆ -alkylene, C ₁ -C ₆ -heteroalkylene, -O-, -C(O)-, - N(R ⁴ )-, -N(R ⁴ )C(O)-, -C(O)N(R ⁴ )-, -N(R ⁴ )C(O)N(R ⁴ )-, or C ₁ -C ₆ -alkylene-N(R ⁴ )C(O)N(R ⁴ )-, wherein each alkylene and heteroalkylene is optionally substituted with one or more R ⁵ ; X, Y, and Z are each N or C(R ⁶ ), wherein at least one of X, Y, and Z is N; each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene- heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , – C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7- membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , – C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁴ is independently hydrogen, C ₁ -C ₆ - alkyl, or C ₁ -C ₆ -haloalkyl; each R ⁵ is C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ - heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, oxo, –OR ^A , or –NR ^B R ^C ; each R ⁶ is independently hydrogen, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or – S(O) _x R ^D , wherein each alkyl, alkylene, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁹ ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A , wherein each alkyl, alkylene, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁹ ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene- heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ -C ₆ -alkyl; m is 0 or 1; n is 0, 1, or 2; and x is 0, 1, or 2. In an embodiment, when X is CH and Y and Z are each independently N, one of L ¹ and L ² is independently not N(CH ₃ ) or O. In an embodiment, when X is CH and Y and Z are each independently N, L ¹ is not N(CH ₃ ) or O. In an embodiment, when X is CH and Y and Z are each independently N, L ² is not N(CH ₃ ) or O. In an embodiment, when X is CH and Y and Z are each independently N, each of L ¹ and L ² is independently not N(CH ₃ ) or O. In another aspect, the present invention features a compound of Formula (II): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; L ¹ and L ² are each independently absent, C ₁ -C ₆ -alkylene, C ₁ -C ₆ -heteroalkylene, -O-, -C(O)-, - N(R ⁴ )-, -N(R ⁴ )C(O)-, -C(O)N(R ⁴ )-, -N(R ⁴ )C(O)N(R ⁴ )-, or C ₁ -C ₆ -alkylene-N(R ⁴ )C(O)N(R ⁴ )-, wherein each alkylene and heteroalkylene is optionally substituted with one or more R ⁵ ; W and Z are each N or C(R ⁶ ), wherein at least one of W and Z is N; each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ - alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D , or –S(O) _x R ^D ; each R ⁴ is independently hydrogen, C ₁ -C ₆ -alkyl, or C ₁ -C ₆ -haloalkyl; each R ⁵ is C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, oxo, –OR ^A , or –NR ^B R ^C ; each R ⁶ is independently hydrogen, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ - heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ - C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁹ ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-cycloalkyl, C ₁ -C ₆ alkylene- heterocyclyl, –OR ^A , wherein each alkyl, alkylene, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁹ ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ - C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene-heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ - C ₆ -alkyl; m and n are each independently 0, 1, or 2; and x is 0, 1, or 2. As generally described herein for compounds of Formula (I) and (II), each of A or B are independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ . In some embodiments, each of A and B are independently a monocyclic ring, e.g., monocyclic cycloalkyl, monocyclic heterocyclyl, monocyclic aryl, or monocyclic heteroaryl. The monocyclic ring may be saturated, partially unsaturated, or fully unsaturated (e.g., aromatic). In some embodiments, A or B are independently a monocyclic ring comprising between 3 and 10 ring atoms (e.g., 3, 4, 5, 6, 7, 8, 9, or 10 ring atoms). In some embodiments, A is a 4-membered monocyclic ring. In some embodiments, B is a 4-membered monocyclic ring. In some embodiments, A is a 5-membered monocyclic ring. In some embodiments, B is a 5-membered monocyclic ring. In some embodiments, A is a 6-membered monocyclic ring. In some embodiments, B is a 6-membered monocyclic ring. In some embodiments, A is a 7-membered monocyclic ring. In some embodiments, B is a 7-membered monocyclic ring. In some embodiments, A is an 8-membered monocyclic ring. In some embodiments, B is an 8-membered monocyclic ring. In some embodiments, A or B are independently a monocyclic ring optionally substituted with one or more R ¹ . In some embodiments, A or B are independently a bicyclic ring, e.g., bicyclic cycloalkyl, bicyclic heterocyclyl, bicyclic aryl, or bicyclic heteroaryl. The bicyclic ring may be saturated, partially unsaturated, or fully unsaturated (e.g., aromatic). In some embodiments, A or B are independently a bicyclic ring comprising a fused, bridged, or spiro ring system. In some embodiments, A or B are independently a bicyclic ring comprising between 4 and 18 ring atoms (e.g., 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 ring atoms). In some embodiments, A is a 6-membered bicyclic ring. In some embodiments, B is a 6-membered bicyclic ring. In some embodiments, A is a 7-membered bicyclic ring. In some embodiments, B is a 7-membered bicyclic ring. In some embodiments, A is an 8-membered bicyclic ring. In some embodiments, B is an 8-membered bicyclic ring. In some embodiments, A is a 9-membered bicyclic ring. In some embodiments, B is a 9-membered bicyclic ring. In some embodiments, A is a 10- membered bicyclic ring. In some embodiments, B is a 10-membered bicyclic ring. In some embodiments, A is an 11-membered bicyclic ring. In some embodiments, B is an 11-membered bicyclic ring. In some embodiments, A is a 12-membered bicyclic ring. In some embodiments, B is a 12-membered bicyclic ring. In some embodiments, A or B are independently a bicyclic ring optionally substituted with one or more R ¹ . In some embodiments, A or B are independently a tricyclic ring, e.g., tricyclic cycloalkyl, tricyclic heterocyclyl, tricyclic aryl, or tricyclic heteroaryl. The tricyclic ring may be saturated, partially unsaturated, or fully unsaturated (e.g., aromatic). In some embodiments, A or B are independently a tricyclic ring that comprises a fused, bridged, or spiro ring system, or a combination thereof. In some embodiments, A or B are independently a tricyclic ring comprising between 6 and 24 ring atoms (e.g., 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 ring atoms). In some embodiments, A is an 8-membered tricyclic ring. In some embodiments, B is an 8-membered tricyclic ring. In some embodiments, A is a 9- membered tricyclic ring. In some embodiments, B is a 9-membered tricyclic ring. In some embodiments, A is a 10-membered tricyclic ring. In some embodiments, B is a 10-membered tricyclic ring. In some embodiments, A or B are independently a tricyclic ring optionally substituted with one or more R ¹ . In some embodiments, A or B are independently monocyclic cycloalkyl, monocyclic heterocyclyl, monocyclic aryl, or monocyclic heteroaryl. In some embodiments, A or B are independently bicyclic cycloalkyl, bicyclic heterocyclyl, bicyclic aryl, or bicyclic heteroaryl. In some embodiments, A or B are independently tricyclic cycloalkyl, tricyclic heterocyclyl, tricyclic aryl, or tricyclic heteroaryl. In some embodiments, A is monocyclic heterocyclyl. In some embodiments, B is monocyclic heterocyclyl. In some embodiments, A is bicyclic heterocyclyl. In some embodiments, B is bicyclic heterocyclyl. In some embodiments, A is monocyclic heteroaryl. In some embodiments, B is monocyclic heteroaryl. In some embodiments, A is bicyclic heteroaryl. In some embodiments, B is bicyclic heteroaryl. In some embodiments, A or B are independently a nitrogen-containing heterocyclyl, e.g., heterocyclyl comprising one or more nitrogen atom. The one or more nitrogen atom of the nitrogen-containing heterocyclyl may be at any position of the ring. In some embodiments, the nitrogen-containing heterocyclyl is monocyclic, bicyclic, or tricyclic. In some embodiments, A or B are independently heterocyclyl comprising at least 1, at least 2, at least 3, at least 4, at least 5, or at least 6 nitrogen atoms. In some embodiments, A is heterocyclyl comprising 1 nitrogen atom. In some embodiments, B is heterocyclyl comprising 1 nitrogen atom. In some embodiments, A is heterocyclyl comprising 2 nitrogen atoms. In some embodiments, B is heterocyclyl comprising 2 nitrogen atoms. In some embodiments, A is heterocyclyl comprising 3 nitrogen atoms. In some embodiments, B is heterocyclyl comprising 3 nitrogen atoms. In some embodiments, A is heterocyclyl comprising 4 nitrogen atoms. In some embodiments, B is heterocyclyl comprising 4 nitrogen atoms. In some embodiments, A or B are independently a nitrogen-containing heterocyclyl comprising one or more additional heteroatoms, e.g., one or more of oxygen, sulfur, boron, silicon, or phosphorus. In some embodiments, the one or more nitrogen of the nitrogen-containing heterocyclyl is substituted, e.g., with R ¹ . In some embodiments, A or B are independently a nitrogen-containing heteroaryl, e.g., heteroaryl comprising one or more nitrogen atom. The one or more nitrogen atom of the nitrogen-containing heteroaryl may be at any position of the ring. In some embodiments, the nitrogen-containing heteroaryl is monocyclic, bicyclic, or tricyclic. In some embodiments, A or B are independently heteroaryl comprising at least 1, at least 2, at least 3, at least 4, at least 5, or at least 6 nitrogen atoms. In some embodiments, A is heteroaryl comprising 1 nitrogen atom. In some embodiments, B is heteroaryl comprising 1 nitrogen atom. In some embodiments, A is heteroaryl comprising 2 nitrogen atoms. In some embodiments, B is heteroaryl comprising 2 nitrogen atoms. In some embodiments, A is heteroaryl comprising 3 nitrogen atoms. In some embodiments, B is heteroaryl comprising 3 nitrogen atoms. In some embodiments, A is heteroaryl comprising 4 nitrogen atoms. In some embodiments, B is heteroaryl comprising 4 nitrogen atoms. In some embodiments, A or B are independently a nitrogen-containing heteroaryl comprising one or more additional heteroatoms, e.g., one or more of oxygen, sulfur, boron, silicon, or phosphorus. In some embodiments, the one or more nitrogen of the nitrogen- containing heteroaryl is substituted, e.g., with R ¹ . In some embodiments, A is a 6-membered nitrogen-containing heterocyclyl, e.g., a 6- membered heterocyclyl comprising one or more nitrogen. In some embodiments, A is a 6- membered heterocyclyl comprising 1 nitrogen atom. In some embodiments, A is a 6-membered heterocyclyl comprising 2 nitrogen atoms. In some embodiments, A is a 6-membered heterocyclyl comprising 3 nitrogen atoms. In some embodiments, A is a 6-membered heterocyclyl comprising 4 nitrogen atoms. The one or more nitrogen atom of the 6-membered nitrogen-containing heterocyclyl may be at any position of the ring. In some embodiments, A is a 6-membered nitrogen-containing heterocyclyl optionally substituted with one or more R ¹ . In some embodiments, the one or more nitrogen of the 6-membered nitrogen-containing heterocyclyl is substituted, e.g., with R ¹ . In some embodiments, A is a 6-membered nitrogen- containing heterocyclyl comprising one or more additional heteroatoms, e.g., one or more of oxygen, sulfur, boron, silicon, or phosphorus. In some embodiments, B is a 5-membered nitrogen-containing heterocyclyl or heteroaryl, e.g., a 5-membered heterocyclyl or heteroaryl comprising one or more nitrogen. In some embodiments, B is a 5-membered heterocyclyl comprising 1 nitrogen atom. In some embodiments, B is a 5-membered heteroaryl comprising 1 nitrogen atom. In some embodiments, B is a 5-membered heterocyclyl comprising 2 nitrogen atoms. In some embodiments, B is a 5- membered heteroaryl comprising 2 nitrogen atoms. In some embodiments, B is a 5-membered heterocyclyl comprising 3 nitrogen atoms. In some embodiments, B is a 5-membered heteroaryl comprising 3 nitrogen atoms. The one or more nitrogen atom of the 5-membered nitrogen- containing heterocyclyl or heteroaryl may be at any position of the ring. In some embodiments, B is a 5-membered nitrogen-containing heterocyclyl optionally substituted with one or more R ¹ . In some embodiments, B is a 5-membered nitrogen-containing heteroaryl optionally substituted with one or more R ¹ . In some embodiments, the one or more nitrogen of the 5-membered nitrogen-containing heterocyclyl or heteroaryl is substituted, e.g., with R ¹ . In some embodiments, B is a 5-membered nitrogen-containing heterocyclyl or heteroaryl comprising one or more additional heteroatoms, e.g., one or more of oxygen, sulfur, boron, silicon, or phosphorus. In some embodiments, B is a nitrogen-containing bicyclic heteroaryl (e.g., a 9-membered nitrogen-containing bicyclic heteroaryl), that is optionally substituted with one or more R ¹ . In some embodiments, B is a 9-membered bicyclic heteroaryl comprising 1 nitrogen atom. In some embodiments, B is a 9-membered bicyclic heteroaryl comprising 2 nitrogen atoms. In some embodiments, B is a 9-membered bicyclic heteroaryl comprising 3 nitrogen atoms. In some embodiments, B is a 9-membered bicyclic heteroaryl comprising 4 nitrogen atoms. The one or more nitrogen atom of the 9-membered bicyclic heteroaryl may be at any position of the ring. In some embodiments, B is a 9-membered bicyclic heteroaryl substituted with one or more R ¹ . In some embodiments, each of A and B are independently selected from: ,

,

each R ¹ is as defined herein. In an embodiment, A and B are each independently a saturated, partially saturated, or unsaturated (e.g., aromatic) derivative of one of the rings described above. In an embodiment, A and B are each independently a stereoisomer of one of the rings described above. In some embodiments, each of A and B are independently selected from: ,

wherein each R ¹ is as defined herein. In an embodiment, A and B are each independently a saturated, partially saturated, or unsaturated (e.g., aromatic) derivative of one of the rings described above. In an embodiment, A and B are each independently a stereoisomer of one of the rings described above. For each of Formulas (I) or (II), in some embodiments, one of A and B is independently a monocyclic heteroaryl or bicyclic heteroaryl, each of which is optionally substituted with one or more R ¹ . In some embodiments, one of A and B is independently a bicyclic heteroaryl optionally substituted with one or more R ¹ . In some embodiments, one of A and B is independently a nitrogen-containing heteroaryl optionally substituted with one or more R ¹ . In some embodiments, one of A and B is independently selected from ,

,

For each of Formulas (I) or (II), in some embodiments, one of A and B is independently a monocyclic heterocyclyl or bicyclic heterocyclyl, each of which is optionally substituted with one or more R ¹ . In some embodiments, one of A and B is independently a monocyclic heterocyclyl optionally substituted with one or more R ¹ . In some embodiments, one of A and B is independently a bicyclic heterocyclyl optionally substituted with one or more R ¹ . In some embodiments, one of A and B is independently a nitrogen-containing heterocyclyl optionally substituted with one or more R ¹ . In some embodiments, one of A and B is independently In some embodiments, one of A and B is independently , and each of R ^B1 and R ^C1 is selected from hydrogen, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, C ₁ -C ₆ alkylene-cycloalkyl, and C ₁ -C ₆ alkylene-heterocyclyl, wherein each alkyl, alkylene, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl is optionally substituted with one or more R ⁹ . In some embodiments, R ^B1 is hydrogen and R ^C1 is selected from hydrogen, C ₁ -C ₆ - alkyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, C ₁ -C ₆ alkylene-cycloalkyl, and C ₁ -C ₆ alkylene-heterocyclyl, wherein each alkyl, alkylene, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl is optionally substituted with one or more R ⁹ . In some embodiments, one of A and B is independently selected from , and each of R ^B1 and R ^C1 is selected from hydrogen, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ - haloalkyl, cycloalkyl, heterocyclyl, C ₁ -C ₆ alkylene-cycloalkyl, and C ₁ -C ₆ alkylene-heterocyclyl, wherein each alkyl, alkylene, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl is optionally substituted with one or more R ⁹ . In some embodiments, R ^B1 is hydrogen and R ^C1 is selected from hydrogen, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, C ₁ -C ₆ alkylene-cycloalkyl, and C ₁ -C ₆ alkylene-heterocyclyl, wherein each alkyl, alkylene, heteroalkyl, haloalkyl, cycloalkyl, and heterocyclyl is optionally substituted with one or more R ⁹ . In some embodiments, one of A and B is independently is selected

, , As generally described for Formulas (I) and (II), each of L ¹ and L ² may independently be absent or refer to a C ₁ -C ₆ -alkylene, C ₁ -C ₆ -heteroalkylene, -O-, -C(O)-, -N(R ⁸ )-, -N(R ⁸ )C(O)-, or -C(O)N(R ⁸ )- group, wherein each alkylene and heteroalkylene is optionally substituted with one or more R ⁹ . In some embodiments, L ¹ is absent or C ₁ -C ₆ -heteroalkylene. In some embodiments, L ¹ is absent. In some embodiments, L ¹ is C ₁ -C ₆ -heteroalkylene (e.g., -N(CH ₃ )-). In some embodiments, L ² is absent or C ₁ -C ₆ -heteroalkylene. In some embodiments, L ² is absent. In some embodiments, L ² is C ₁ -C ₆ -heteroalkylene (e.g., -N(CH ₃ )-). As generally described for Formulas (I) and (II), each R ² and R ³ is independently C ₁ -C ₆ - alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D , or –S(O) _x R ^D . In some embodiments, R ² is C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D . In some embodiments, R ² is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D ,–C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D . In some embodiments, R ² is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -heteroalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , or -C(O)NR ^B R ^C . In some embodiments, R ² is C ₁ -C ₆ -alkyl. In some embodiments, R ² is C ₁ -C ₆ -heteroalkyl. In some embodiments, R ² is halo (e.g., chloro or fluoro). In some embodiments, R ² is cyano. In some embodiments, R ² is cycloalkyl (e.g., cyclopropyl or cyclobutyl). In some embodiments, R ² is heterocyclyl. In some embodiments, R ² is heteroaryl. In some embodiments, R ² is –OR ^A . In some embodiments, R ² is -C(O)NR ^B R ^C . In some embodiments, R ³ is C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ - heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , – NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D . In some embodiments, R ³ is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D ,–C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D . In some embodiments, R ³ is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -heteroalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , or -C(O)NR ^B R ^C . In some embodiments, R ³ is C ₁ -C ₆ -alkyl. In some embodiments, R ³ is C ₁ -C ₆ -heteroalkyl. In some embodiments, R ³ is halo (e.g., chloro or fluoro). In some embodiments, R ³ is cyano. In some embodiments, R ³ is cycloalkyl (e.g., cyclopropyl or cyclobutyl). In some embodiments, R ³ is heterocyclyl. In some embodiments, R ³ is heteroaryl. In some embodiments, R ³ is –OR ^A . In some embodiments, R ³ is -C(O)NR ^B R ^C . In some embodiments, R ¹ is C ₁ -C ₆ -alkyl. In some embodiments, R ¹ is CH ₃ . In some embodiments, A is substituted with 0 or 1 R ¹ . In some embodiments, B is substituted with 0, 1, or 2 R ¹ . In some embodiments, the compound of Formula (I) is a compound of Formula (I-a): (I-a), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; L ¹ and L ² are each independently absent, C ₁ -C ₆ -alkylene, C ₁ -C ₆ -heteroalkylene, -O-, -C(O)-, - N(R ⁴ )-, -N(R ⁴ )C(O)-, -C(O)N(R ⁴ )-, -N(R ⁴ )C(O)N(R ⁴ )-, or C ₁ -C ₆ -alkylene-N(R ⁴ )C(O)N(R ⁴ )-, wherein each alkylene and heteroalkylene is optionally substituted with one or more R ⁵ ; X and Y are each N or C(R ⁶ ); each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ - alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, heteroaryl, aryl, C ₁ -C ₆ alkylene-aryl, C ₂ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, halo, cyano, oxo, –OR ^A , – NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkenylene, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁴ is independently hydrogen, C ₁ -C ₆ -alkyl, or C ₁ -C ₆ -haloalkyl; each R ⁵ is C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, oxo, –OR ^A , or –NR ^B R ^C ; each R ⁶ is independently hydrogen, halo, cyano, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , – NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkylene- heteroaryl, –C(O)R ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁹ ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-cycloalkyl, C ₁ -C ₆ alkylene- heterocyclyl, –OR ^A , wherein each alkyl, alkylene, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁹ ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ - C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, and haloalkyl is optionally substituted with one or more R ⁹ ; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ -C ₆ -alkyl; n is 0, 1, or 2; m is 0 or 1; and x is 0, 1, or 2. In some embodiments, the compound of Formula (I) is a compound of Formula (I-a-i): (I-a-i), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; L ¹ and L ² are each independently absent, C ₁ -C ₆ -alkylene, C ₁ -C ₆ -heteroalkylene, -O-, -C(O)-, - N(R ⁴ )-, -N(R ⁴ )C(O)-, -C(O)N(R ⁴ )-, -N(R ⁴ )C(O)N(R ⁴ )-, or C ₁ -C ₆ -alkylene-N(R ⁴ )C(O)N(R ⁴ )-, wherein each alkylene and heteroalkylene is optionally substituted with one or more R ⁵ ; X and Y are each N or C(R ⁶ ); each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ - alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, heteroaryl, aryl, C ₁ -C ₆ alkylene-aryl, C ₂ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, halo, cyano, oxo, –OR ^A , – NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkenylene, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , – C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁴ is independently hydrogen, C ₁ -C ₆ - alkyl, or C ₁ -C ₆ -haloalkyl; each R ⁵ is C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ - heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, oxo, –OR ^A , or –NR ^B R ^C ; each R ⁶ is independently hydrogen, halo, cyano, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ - alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , – C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkylene- heteroaryl, –C(O)R ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁹ ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-cycloalkyl, C ₁ -C ₆ alkylene- heterocyclyl, –OR ^A , wherein each alkyl, alkylene, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁹ ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ - C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, and haloalkyl is optionally substituted with one or more R ⁹ ; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ -C ₆ -alkyl; n is 0, 1, or 2; m is 0 or 1; and x is 0, 1, or 2. In some embodiments, the compound of Formula (I) is a compound of Formula (I-b): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; X, Y, and Z are each N or C(R ⁶ ), wherein at least one of X, Y, and Z is N; each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene- heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , – C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7- membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , – C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁶ is independently hydrogen, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ - heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ - C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or – S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3- 7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene- heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ -C ₆ -alkyl; m and n are each independently 0, 1, or 2; and x is 0, 1, or 2. In some embodiments, each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ - alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D . In some embodiments, the compound of Formula (I) is a compound of Formula (I-c): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; X, and Y are each N or C(R ⁶ );each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ - C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene- aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , – NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁶ is independently hydrogen, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene- aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or –S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ - C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene-heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ - C ₆ -alkyl; m and n are each independently 0, 1, or 2; and x is 0, 1, or 2. each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or – S(O) _x R ^D . In some embodiments, the compound of Formula (I) is a compound of Formula (I-d): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; X and Z are each N or C(R ⁶ );each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ - C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene- aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , – NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁶ is independently hydrogen, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene- aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or –S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ - C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene-heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ - C ₆ -alkyl; m and n are each independently 0, 1, or 2; and x is 0, 1, or 2. each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or – S(O) _x R ^D . In some embodiments, the compound of Formula (I) is a compound of Formula (I-e): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; X is N or C(R ⁶ );each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ - C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁶ is independently hydrogen, halo, C ₁ - C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ - alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or – S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, C ₁ - C ₆ alkylene-heteroaryl, –C(O)R ^D , or –S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene- aryl, or C ₁ -C ₆ alkylene-heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ - C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ - C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ -C ₆ -alkyl; m and n are each independently 0, 1, or 2; and x is 0, 1, or 2. each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ - alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D . In some embodiments, the compound of Formula (I) is a compound of Formula (I-f): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ - heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ - alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene- aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or –S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ - C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene-heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ - C ₆ -alkyl; m and n are each independently 0, 1, or 2; and x is 0, 1, or 2. each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or – S(O) _x R ^D . In some embodiments, the compound of Formula (I) is a compound of Formula (I-g): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; Y is N or C(R ⁶ );each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ - C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁶ is independently hydrogen, halo, C ₁ - C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ - alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or – S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, C ₁ - C ₆ alkylene-heteroaryl, –C(O)R ^D , or –S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene- aryl, or C ₁ -C ₆ alkylene-heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ - C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ - C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ -C ₆ -alkyl; m and n are each independently 0, 1, or 2; and x is 0, 1, or 2. each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ - alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D . In some embodiments, the compound of Formula (I) is a compound of Formula (I-h): ( ), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ - heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ - alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene- aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or –S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ - C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene-heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ - C ₆ -alkyl; m and n are each independently 0, 1, or 2; and x is 0, 1, or 2. each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or – S(O) _x R ^D . In some embodiments, the compound of Formula (I) is a compound of Formula (I-h-i): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ - heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ - alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene- aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or –S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ - C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene-heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ - C ₆ -alkyl; m and n are each independently 0, 1, or 2; and x is 0, 1, or 2. In some embodiments, the compound of Formula (I) is a compound of Formula (I-h-ii): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; L ¹ and L ² are each independently absent, C ₁ -C ₆ -alkylene, C ₁ -C ₆ -heteroalkylene, -O-, -C(O)-, - N(R ⁴ )-, -N(R ⁴ )C(O)-, -C(O)N(R ⁴ )-, -N(R ⁴ )C(O)N(R ⁴ )-, or C ₁ -C ₆ -alkylene-N(R ⁴ )C(O)N(R ⁴ )-, wherein each alkylene and heteroalkylene is optionally substituted with one or more R ⁵ ; X, Y, and Z are each N or C(R ⁶ ), wherein at least one of X, Y, and Z is N; each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene- heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , – C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7- membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ³ is independently C ₁ - C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁴ is independently hydrogen, C ₁ -C ₆ -alkyl, or C ₁ -C ₆ - haloalkyl; each R ⁵ is C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ - haloalkyl, halo, cyano, oxo, –OR ^A , or –NR ^B R ^C ; each R ⁶ is independently hydrogen, halo, C ₁ -C ₆ - alkyl, C ₁ -C ₆ -haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ - alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or – S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or – S(O) _x R ^D , wherein each alkyl, alkylene, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁹ ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A , wherein each alkyl, alkylene, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁹ ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene- heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ -C ₆ -alkyl; m is 0 or 1; n is 0, 1, or 2; and x is 0, 1, or 2. In an embodiment, when X is CH and Y and Z are each independently N, one of L ¹ and L ² is independently not N(CH ₃ ) or O. In an embodiment, when X is CH and Y and Z are each independently N, L ¹ is not N(CH ₃ ) or O. In an embodiment, when X is CH and Y and Z are each independently N, L ² is not N(CH ₃ ) or O. In an embodiment, when X is CH and Y and Z are each independently N, each of L ¹ and L ² is independently not N(CH ₃ ) or O. In some embodiments, the compound of Formula (I) is a compound of Formula (I-i): ( ), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A’ is bicyclic heteroaryl or heterocyclyl; B is cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; X, Y, and Z are each N or C(R ⁶ ), wherein at least one of X, Y, and Z is N; each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ - haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , – C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3- 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; R ^1a is C ₁ -C ₆ -alkyl, C ₁ -C ₆ - heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D ,–C(O)NR ^B R ^C , –C(O)R ^D , or – C(O)OR ^D ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ - heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁶ is independently hydrogen, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene- aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or –S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ - C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene-heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ - C ₆ -alkyl; m and n are each independently 0, 1, or 2; and x is 0, 1, or 2. In some embodiments, the compound of Formula (I) is a compound of Formula (I-j): j or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A is cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; B’ is bicyclic heteroaryl or heterocyclyl; X, Y, and Z are each N or C(R ⁶ ), wherein at least one of X, Y, and Z is N; each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ - C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , – C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3- 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; R ^1a is C ₁ -C ₆ -alkyl, C ₁ -C ₆ - heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D ,–C(O)NR ^B R ^C , –C(O)R ^D , or – C(O)OR ^D ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ - heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁶ is independently hydrogen, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene- aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or –S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ - C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene-heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ - C ₆ -alkyl; m and n are each independently 0, 1, or 2; and x is 0, 1, or 2. In some embodiments, the compound of Formula (I) is a compound of Formula (I-k): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A is cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; X, Y, and Z are each N or C(R ⁶ ), wherein at least one of X, Y, and Z is N; each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, – OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁶ is independently hydrogen, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene- aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or –S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ - C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene-heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ - C ₆ -alkyl; m and n are each independently 0, 1, or 2; p is 0, 1, 2, or 3; and x is 0, 1, or 2. In some embodiments, the compound of Formula (I) is a compound of Formula (I-l): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein B is cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; X, Y, and Z are each N or C(R ⁶ ), wherein at least one of X, Y, and Z is N; each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, – OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁶ is independently hydrogen, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , – C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene- aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or –S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ - C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene-heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ - C ₆ -alkyl; m and n are each independently 0, 1, or 2; p is 0, 1, 2, or 3; q is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14; and x is 0, 1, or 2. In some embodiments, the compound of Formula (I) is selected from a compound in Table 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 100, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 101, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-6-hydroxy- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 102, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-hydroxy-2- methylimidazo[1,2-b]pyridazinyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 103, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X and Z are N; Y is C(R ^5a ) (e.g., -CH-); and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 104, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 4-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 105, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 4-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X and Z are N; Y is C(R ^5a ) (e.g., -CH-); and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 106, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 107, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 4-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 108, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X and Y are independently C(R ^5a ) (e.g., -CH-); Z is N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 109, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; R ² is halo (e.g., fluoro); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 113, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; R ³ is halo (e.g., fluoro); m is 0; and n is 1. In some embodiments, the compound of Formula (I) is Compound 114, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y is C(R ^5a ) (e.g., -CF-); Z is N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 115, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., N-methyl-piperazyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 116, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2-methylpiperazyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 117, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., N-methyl-2-methylpiperazyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 118, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2-ethylpiperazyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 119, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,2-dimethylpiperazyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 120, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 4,7-diazaspiro[2.5]octanyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 121, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperazyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 122, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 2-methyl-2,6-diazaspiro[3.3]heptanyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 123, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 2,6-diazaspiro[3.3]heptanyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 124, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 1,3-bipyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 125, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., N-methylpiperidinyl); L ¹ is absent; L ² is -N(R ⁴ )- (e.g., -N(CH ₃ )-); X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 126, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert-butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 127, 153, 154, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N,N- (dimethyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 129, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl); L ¹ is absent; L ² is -N(R ⁴ )- (e.g., -N(CH ₃ )-); X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 130, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(N-(ethyl)amino)piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 131, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(N-(tert-butyl)amino)piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 132, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(N,N-(dimethyl)amino)piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 133, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., octahydropyrrolo[1,2-a]pyrazinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 134, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 3,6-diazabicyclo[3.1.1]heptanyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 135, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 136, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 137, 545, 546, 547, 548, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., N-ethylpiperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 138, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2-methylpiperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 139, 140, 549, 550, 551, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 4-hydroxy-7- bromo-2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; Y is C(R ^5a ) (e.g., -CH-); X and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 141, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., N-methylpiperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 142, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-methoxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y is C(R ^5a ) (e.g., -CF-); Z is N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 143, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is N; Y and Z are each independently is C(R ^5a ) (e.g., -CH-); R ³ is halo (e.g., fluoro); m is 0; and n is 1. In some embodiments, the compound of Formula (I) is Compound 144, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-methoxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is N; Y and Z are each independently is C(R ^5a ) (e.g., -CH-); R ³ is halo (e.g., fluoro); m is 0; and n is 1. In some embodiments, the compound of Formula (I) is Compound 145, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 146, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 147, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]thiazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 148, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-hydroxy-2- methylimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 149, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 3-hydroxy-4,6- dimethylpyrazolo[1,5-a]pyrazinyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 150, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-hydroxy-2,8- dimethylimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 151, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heteroaryl (e.g., 1H-imidazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 152, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-6-hydroxy- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 155, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(cyclobutyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 156, 157, 262, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 158, 197, 198, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., azetidinyl); L ¹ is absent; L ² is -O-; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 159, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is tricyclic heterocyclyl (e.g., octahydro-1H-6^ ² -cyclopenta[2,1-b:5,1- b']dipyrrolyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 160, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6- methoxyisoquinolinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert-butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 161, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 1,6-diazaspiro[3.4]octanyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 162, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 1,6-diazaspiro[3.5]nonanyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 163, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 1,7-diazaspiro[3.5]nonanyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 164, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert-butyl)amino)azetidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 165, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy- isoquinolinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert-butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 166, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-3- methylquinazolin-4(3H)-onyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 167, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-methoxy-3- methylquinazolin-4(3H)-onyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 168, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 7-methyl-1,7-diazaspiro[3.5]nonanyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 169, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(methyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 170, 172, 263, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(isopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 171, 173, 264, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-4H-chromen-4-onyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 174, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 175, 209, 210, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-methoxy-2- methylbenzo[d]thiazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 176, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-methoxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 177, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 1,6-diazaspiro[3.4]octanyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 178, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(ethyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 179, 180, 265, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 1-methyl-1,6-diazaspiro[3.4]octanyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 181, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-( 2,2,2- trifluoroethyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 182, 245, 266, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-fluoro-2-methyl- 2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert-butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 183, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2-methyl-2H- indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 184, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-2-methyl- 2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 185, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2,8- dimethylimidazo[1,2-b]pyridazinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 186, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 4,6- dimethylpyrazolo[1,5-a]pyrazinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 187, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(oxetanyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 188, 189, 267, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]thiazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 190, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 191, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 6-methyl-1,6-diazaspiro[3.5]nonanyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 192, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-fluoro-2-methyl- 2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 193, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (methylcyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 194, 195, 268, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-(difluoromethyl)- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 196, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2-methyl-2H- pyrazolo[4,3-b]pyridinyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 199, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2-methyl-2H- pyrazolo[3,4-c]pyridinyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 200, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2,8- dimethylimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 201, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-6-hydroxy- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 202, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 3-hydroxy-4,6- dimethylpyrazolo[1,5-a]pyrazinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 203, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-cyano-2-methyl- 2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 204, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-fluoro-2-methyl- 2H-pyrazolo[4,3-b]pyridinyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 205, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2,8- dimethylimidazo[1,2-a]pyrazinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 206, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-fluoro-2-methyl- 2H-pyrazolo[4,3-b]pyridinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 207, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2,7-dimethyl-2H- pyrazolo[3,4-c]pyridinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 208, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 211, 212, 271, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is 214, 215, 272, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 216, 217, 273, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert-butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; Y is C(R ^5a ) (e.g., -CH-); X and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 218, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(1- methylcyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 219, 220, 221, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(1- methylcyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 222, 223, 274, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(1- methylcyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 224, 225, 226, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclobutyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 228, 229, 230, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (isopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 231, 232, 233, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3- aminopyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 234, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclobutyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is 235, 236, 237, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-aminopyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 238, 362, 363, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X and Y are each independently C(R ^5a ) (e.g., -CH-); Z is N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 241, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(3- fluorocyclobutyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 246, 247, 277, 299, 300, 552, 609, 610, 611, 612, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2,7-dimethyl-2H- pyrazolo[4,3-b]pyridinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 248, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 249, 250, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-methoxy-7- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert-butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 251, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 3-hydroxy-4,6- dimethylpyrazolo[1,5-a]pyrazinyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 252, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-4-fluoro- 2-methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 253, 254, 278, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-4-fluoro- 2-methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 255, 256, 279, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(1- methylcyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 257, 258, 280, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 259, 260, 281, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert-butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 282, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(methyl)amino)pyrrolidinyl); L ¹ and L ² are absent; Y is C(R ^5a ) (e.g., -CH-); X and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 283, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (methylcyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 284, 321, 322, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (isopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 285, 286, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 287, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclobutyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 288, 289, 290, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (methylcyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 291, 292, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-4-fluoro- 2-methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclobutyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 293, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-4-fluoro- 2-methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (methylcyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 294, 323, 324, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (methylcyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 295, 296, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(bicyclo[1.1.1]pentan-1- yl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 297, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy- 2- methyl-2H-pyrazolo[4,3-b]pyridinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 298, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; Y is C(R ^5a ) (e.g., -CH-); X and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 301, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(oxetanyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 302, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (methylcyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 303, 304, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 305, 306, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-4-fluoro- 2-methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclobutyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 307, 308, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(1- methylcyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is 309, 310, 311, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (isopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is 312, 313, 314, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclobutyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 315, 316, 317, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (isopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 318, 319, 320, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-4-fluoro- 2-methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(1- methylcyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 325, 326, 327, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-4-fluoro- 2-methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (isopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 328, 329, 330, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-fluoro-2- methylimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., 3-(N- (methyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 331, 332, 393, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- cyclopropylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 333, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- (methoxymethyl)benzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 334, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-methoxy-2- (oxetan-3-yl)benzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 335, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy- 2- (hydroxymethyl)benzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 336, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(methyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 337, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 338, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-1,2- dimethyl-1H-benzo[d]imidazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 339, 340, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(pyrrolidin-3-ylamino)-1-hydroxy- bicyclo[1.1.1]pentanyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 341, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 1,6-diazaspiro[3.4]octanyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 342, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 4,6- dimethylpyrazolo[1,5-a]pyrazinyl); B is monocyclic heterocyclyl (e.g., piperdinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -C(OCH ₃ )-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 343, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5,7- dimethylimidazo[1,2-c]pyrimidinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 344, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazyl); L ¹ and L ² are absent; Y is C(R ^5a ) (e.g., -CH-); X and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 345, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy- 2- (ethyl)benzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 346, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(3- fluorocyclobutyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 347, 349, 613, 614, 615, 616, 617, 618, 619, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(3- fluorocyclobutyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 348, 350, 395, 396, 620, 621, 622, 623, 624, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(3- fluorocyclobutyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 351, 352, 376, 377, 625, 626, 627, 628, 629, 630, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(1- (fluoromethyl)cyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 353, 357, 553, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(1- (fluoromethyl)cyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 354, 355, 554, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2-methylpiperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 356, 555, 556, 557, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(3- fluorocyclobutyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 358, 359, 631, 632, 633, 634, 635, 636, 637, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(1- (fluoromethyl)cyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 360, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; R ³ is (e.g., -CH(OH)CH ₃ ); m is 0; and n is 1. In some embodiments, the compound of Formula (I) is Compound 361, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; R ² is (e.g., -CH(OH)CH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 364, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heterocyclyl (e.g., 1-methyl-4,5,6,7- tetrahydro-1H-pyrazolo[4,3-c]pyridinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 365, 367, 559 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heterocyclyl (e.g., 2-methyl-4,5,6,7- tetrahydro-2H-pyrazolo[4,3-c]pyridinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 366, 490, 558, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heterocyclyl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(methyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 368, 369, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heterocyclyl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 370, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heterocyclyl (e.g., 8-cyano-2- methylimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 371, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-4- fluorobenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(1- (fluoromethyl)cyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 372, 560, 561, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-4-fluoro- 2-methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(1-(fluoromethyl)- cyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 373, 491, 562, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-4-fluoro- 2-methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(3- fluorocyclobutyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 374, 375, 487, 638, 639, 640, 641, 642, 643, 644, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., ., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(1- methylcyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 378, 379, 563, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3- aminopyrrolidinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 380, 381, 564, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heterocyclyl (e.g., 8-cyano-2- methylimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., 3-(N- (methyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 382, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-6-hydroxy- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2-methylpiperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 383, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(3,3- difluorocyclobutyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 384, 385, 565, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-hydroxypiperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 386, 566, 567, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-6-hydroxy- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropylmethyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 387, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-6-hydroxy- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (isopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 388, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropylmethyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 389, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropylmethyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 390, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-6-hydroxy- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 391, 392, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heterocyclyl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., pyrrolidinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 397, 398, 399, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y is C(R ^5a ) (e.g., -C(OH)-); and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 400, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N- (isopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is 401, 402, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heterocyclyl (e.g., 7-cyano-6- hydroxy-2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 403, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); A is bicyclic heteroaryl (e.g., 6-hydroxy-2-methyl-2H-indazolyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 404, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); A is monocyclic heteroaryl (e.g., 3-methoxypyridazinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 405, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-cyano-2- methylimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., 3-(N- (methyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X, Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 406, 407, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 408, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 2-methylpiperazinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 409, 568, 569, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is bicyclic heterocyclyl (e.g., octahydropyrrolo[1,2-a]pyrazinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 410, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is bicyclic heterocyclyl (e.g., 4,7-diazaspiro[2.5]octanyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 411, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is bicyclic heterocyclyl (e.g., 4-(N-(tert-butyl)amino)piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 412, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); A is bicyclic heteroaryl (e.g., 5-hydroxy-2-methylbenzo[d]oxazolyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 413, 414, 570, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N- (isopropyl)amino)pyrrolidinyl); A is bicyclic heteroaryl (e.g., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 415, 416, 571, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); B is bicyclic heteroaryl (e.g., 5-hydroxy-2-methylbenzo[d]oxazolyl); L ¹ and L ² are absent; X and Z are N; Y is C(R ^5a ) (e.g., -CH-); and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 417, 572, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 2-cyclopropylpiperazinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 418, 421, 573, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 2-cyclopropyl-6- methylpiperazinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 419, 574, 575, 576, 577, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 420, 578, 579, 580, 581, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 2-isopropylpiperazinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 422, 582, 583, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 2-tert-butylpiperazinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 423, 492, 584, 585, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is bicyclic heterocyclyl (e.g., 4-(N-amino)piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 424, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is bicyclic heterocyclyl (e.g., 4-(N-methylamino)piperidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 425, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2- methyloxazolo[5,4-b]pyridinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 426, 427, 586, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2,7- dimethyloxazolo[5,4-b]pyridinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 428, 429, 587, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyloxazolo[5,4-b]pyridinyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 430, 431, 588, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropyl)amino)pyrrolidinyl); A is bicyclic heteroaryl (e.g., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 432, 433, 589, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropyl)amino)pyrrolidinyl); A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 434, 435, 590, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); A is bicyclic heteroaryl (e.g., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 436, 437, 591, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropyl)amino)pyrrolidinyl); A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7-dimethyl-2H- indazolyl; L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 438, 439, 592, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropyl)amino)pyrrolidinyl); B is bicyclic heteroaryl (e.g., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); L ¹ and L ² are absent; X and Z are N; Y is C(R ^5a ) (e.g., -CH-); and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 440, 441, 593, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropyl)amino)pyrrolidinyl); B is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); L ¹ and L ² are absent; X and Z are N; Y is C(R ^5a ) (e.g., -CH-); and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 442, 443, 594, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); B is bicyclic heteroaryl (e.g., 5-hydroxy-2,4- dimethylbenzo[d]oxazolyl); L ¹ and L ² are absent; X and Z are N; Y is C(R ^5a ) (e.g., -CH-); and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 444, 445, 595, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N- (cyclopropyl)amino)pyrrolidinyl); B is bicyclic heteroaryl (e.g., 6-hydroxy-2,7-dimethyl-2H- indazolyl); L ¹ and L ² are absent; X and Z are N; Y is C(R ^5a ) (e.g., -CH-); and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 446, 447, 596 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heterocyclyl (e.g., 4- azaspiro[2.5]octanyl); A is bicyclic heteroaryl (e.g., 6-hydroxy-2-methyl-2H-indazolyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 448, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); B is bicyclic heteroaryl (e.g., 6-hydroxy-2-methyl-2H-indazolyl); L ¹ and L ² are absent; X and Z are N; Y is C(R ^5a ) (e.g., -CH-); and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 449, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); B is bicyclic heteroaryl (e.g., 6-hydroxy-2-methyl-2H-indazolyl); L ¹ and L ² are absent; X and Z are N; Y is C(R ^5a ) (e.g., -CH-); and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 450, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N- (methylcyclopropyl)amino)pyrrolidinyl); B is bicyclic heteroaryl (e.g., 6-hydroxy-2-methyl-2H- indazolyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 451, 452, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2,8- dimethylimidazo[1,2-a]pyrazinyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Z are N; Y is C(R ^5a ) (e.g., -CH-); and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 453, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-cyano-6-hydroxy- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 454, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); B is bicyclic heteroaryl (e.g., 6-hydroxy-2-methyl-2H-indazolyl); L ¹ and L ² are absent; X and Z are N; Y is C(R ^5a ) (e.g., -CH-); and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 455, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heterocyclyl (e.g., 4- azaspiro[2.5]octanyl); A is bicyclic heteroaryl (e.g., 6-hydroxy-2-methyl-2H-indazolyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 456, 495, 496, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is monocyclic heteroaryl (e.g., pyrazolyl); B is monocyclic heterocyclyl (e.g., piperidinyl); L ¹ is absent; L ² is -C(O)N(R ⁴ )- (e.g., -C(O)N(H)-); X and Y are each independently C(R ^5a ) (e.g., -CH-); Z is N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 457, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heterocyclyl (e.g., 4- azaspiro[2.5]oct-6-enyl); B is bicyclic heteroaryl (e.g., 6-hydroxy-2-methyl-2H-indazolyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 458, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(methyl)amino)-4- methylpyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 459, 597, 598, 599, 600, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(methyl)amino)-4- fluoropyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 460, 461, 462, 463, 601, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert-butyl)amino)-4- methylpyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 464, 465, 466, 467, 602, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert-butyl)amino)-4- fluoropyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 468, 469, 470, 471, 603, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy- 2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert-butyl)amino)-4- fluoropyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 472, 473, 474, 475, 604, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy- 2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert-butyl)amino)-4- methylpyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 476, 477, 478, 479, 605, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(methyl)amino)-4- methylpyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 480, 481, 606, 607, 608, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X is N; Y and Z are each independently is C(R ^5a ) (e.g., -CH-); R ² is halo (e.g., chloro); R ³ is C ₁ -C ₆ alkyl (e.g., methyl); m is 1; and n is 1. In some embodiments, the compound of Formula (I) is Compound 482, 484, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X is N; Y and Z are each independently is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., - C(O)NHCH ₃ ); R ³ is halo (e.g., fluoro); m is 1; and n is 1. In some embodiments, the compound of Formula (I) is Compound 483, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(N,N-dimethyl)aminopiperidinyl); L ¹ and L ² are absent; X is N; Y and Z are each independently is C(R ^5a ) (e.g., -CH-); R ² is halo (e.g., chloro); R ³ is C ₁ -C ₆ alkyl (e.g., methyl); m is 1; and n is 1. In some embodiments, the compound of Formula (I) is Compound 485, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-methyl)aminopyrrolidinyl); L ¹ and L ² are absent; X is N; Y and Z are each independently is C(R ^5a ) (e.g., -CH-); R ² is halo (e.g., chloro); R ³ is C ₁ -C ₆ alkyl (e.g., methyl); m is 1; and n is 1. In some embodiments, the compound of Formula (I) is Compound 486, 748, 749, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(1- (fluoromethyl)cyclopropyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 488, 489, 645, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy-2- methylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert-butyl)-N- methylamino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 493, 494, 646, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heterocyclyl (e.g., 4- azaspiro[2.5]octanyl); A is bicyclic heteroaryl (e.g., 5-hydroxy-2-methylbenzo[d]oxazolyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 497, 498, 647, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heterocyclyl (e.g., 4- azaspiro[2.5]octanyl); A is bicyclic heteroaryl (e.g., 5-hydroxy-2,6-dimethylbenzo[d]oxazolyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 499, 500, 648, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 501, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)N(CH ₃ ) ₂ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 502, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₂ CH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 503, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-hydroxy-2,8- dimethylimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., 3-(N- (methyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X, Y, and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 504, 649, 650, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-fluoro-2- methylimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 505, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 506, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(N,N-dimethylamino)piperidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., - C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 507, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -NR ^B R ^C (e.g., -NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 508, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -NR ^B R ^C (e.g., -N(CH ₃ ) ₂ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 509, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-methylamino)pyrrolidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., - C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 510, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 511, 651, 652, 653, 654, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2-methylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 512, 655, 656. or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)R ^D (e.g., -C(O)CH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 513, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is cyano; m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 514, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X is N; Y and Z are each independently is C(R ^5a ) (e.g., -CH-); R ³ is halo (e.g., fluoro); m is 0; and n is 1. In some embodiments, the compound of Formula (I) is Compound 515, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-2H- indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X is N; Y and Z are each independently is C(R ^5a ) (e.g., -CH-); R ³ is halo (e.g., fluoro); m is 0; and n is 1. In some embodiments, the compound of Formula (I) is Compound 516, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-fluoro-2- methylimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X is N; Y and Z are each independently is C(R ^5a ) (e.g., -CH-); R ³ is halo (e.g., fluoro); m is 0; and n is 1. In some embodiments, the compound of Formula (I) is Compound 517, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is cycloalkyl (e.g., cyclopropyl); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 518, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is heteroaryl (e.g., thiazolyl); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 519, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 520, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-methyl)aminopyrrolidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 521, 657, 658, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is heteroaryl (e.g., triazolyl); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 522, 538, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NH ₂ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 523, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)OR ^D (e.g., -C(O)OH); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 524, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 525, 659, 660, 661, 662, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X, Y, and Z are N; m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 526, 663, 664, 665, 666, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 527, 667, 668, 669, 670, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(N,N-dimethyl)aminopiperidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., - C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 528, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2-methylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 529, 671, 672, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2-methylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 530, 673, 674, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 531, 675, 676, 677, 678, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 4,7-diazaspiro[2.5]octanyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 532, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X, Y, and Z are N; R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 533, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X, Y, and Z are N; R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 534, 679, 680, 681, 682, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₂ CH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 535, 683, 684, 685, 686, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-methyl)aminopyrrolidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., - C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 536, 537, 687, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., - C(O)NHCH(CH ₃ ) ₂ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 539, 688, 689, 690, 691, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., - C(O)NH(cyclobutyl)); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 540, 692, 693, 694, 695, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is heteroaryl (e.g., tetrazolyl); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 541, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is cycloalkyl (e.g., cyclopropyl); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 542, 696, 697, 698, 699, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-methyl)aminopyrrolidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is cycloalkyl (e.g., cyclopropyl); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 543, 700, 701, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-fluoro-2- methylimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X is N; Y and Z are each independently is C(R ^5a ) (e.g., -CH-); R ³ is halo (e.g., fluoro); m is 0; and n is 1. In some embodiments, the compound of Formula (I) is Compound 544, 702, 703, 704, 705, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(azetidin-1-yl)piperidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 706, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is cyano; m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 707, 708, 709, 710, 711, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NH ₂ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 712, 713, 714, 715, 716, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)R ^D (e.g., -C(O)CH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 717, 718, 719, 720, 721, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(azetidin-1-yl)piperidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 722, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X is N; Y and Z are each independently is C(R ^5a ) (e.g., -CH-); R ² is halo (e.g., chloro); R ³ is C ₁ -C ₆ alkyl (e.g., methyl); m is 1; and n is 1. In some embodiments, the compound of Formula (I) is Compound 723, 724, 725, 726, 727, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 4,7-diazaspiro[2.5]octanyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., -C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 728, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-methyl)aminopyrrolidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., - C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 729, 730, 731, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is heteroaryl (e.g., thiazolyl); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 732, 733734, 735, 736, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., - C(O)NHCH ₂ CH ₂ OH); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 737, 738, 739, 740, 741, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(N,N-dimethyl)aminopiperidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -C(O)NR ^B R ^C (e.g., - C(O)NHCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 742, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 743, 744, 745, 746, 747, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(azetidin-1-yl)piperidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 750, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 751, 752, 753, 754, 755, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(N,N-diethyl)aminopiperidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 756, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(N,N-dimethyl)aminopiperidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 757, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-2-methyl- 2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X is N; Y and Z are each independently is C(R ^5a ) (e.g., -CH-); R ³ is halo (e.g., fluoro); m is 0; and n is 1. In some embodiments, the compound of Formula (I) is Compound 758, 759, 760, 761, 762, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X is N; Y and Z are each independently is C(R ^5a ) (e.g., -CH-); R ³ is halo (e.g., fluoro); m is 0; and n is 1. In some embodiments, the compound of Formula (I) is Compound 763, 764, 765, 766, 767, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X is N; Y and Z are each independently is C(R ^5a ) (e.g., -CH-); R ³ is halo (e.g., fluoro); m is 0; and n is 1. In some embodiments, the compound of Formula (I) is Compound 768, 769, 770, 771, 772, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-fluoro-2- methylimidazo[1,2-a]pyridinyl; B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 773, 774, 775, 776, 777, 803, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is -OR ^A (e.g., -OCH ₃ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 778, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-fluoro-2- methylimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is –C(O)NR ^B R ^C (e.g., - C(O)NH(cyclobutyl)); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 779, 839, 840, 841, 842, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-2-methyl- 2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 780, 802, 843, 844, 845, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-2-methyl- 2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is C ₁ -C ₆ -alkyl (e.g., methyl); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 781, 849, 850, 851, 852, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is C ₁ -C ₆ -alkyl (e.g., methyl); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 782, 806, 846, 847, 848, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is C ₁ -C ₆ -alkyl (e.g., methyl); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 783, 807, 853, 854, 855, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is –C(O)NR ^B R ^C (e.g., –C(O)NH ₂ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 784, 796, 856, 857, 858, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is –C(O)NR ^B R ^C (e.g., –C(O)NH ₂ ); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 785, 797, 859, 860, 861, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(azetidin-1-yl)piperidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 786, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-2-methyl- 2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(azetidin-1-yl)piperidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 787, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-2-methyl- 2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(azetidin-1-yl)piperidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is C ₁ -C ₆ -alkyl (e.g., methyl); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 788, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 7-fluoro-2-methyl- 2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2-methylpiperazinyl); L ¹ and L ² are absent; Y is N; X and Z are C(R ^5a ) (e.g., -CH-); R ³ is halo (e.g., fluoro); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 789, 862, 863, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is C ₁ -C ₆ -alkyl (e.g., cyclobutyl); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 790, 794, 864, 865, 866, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is C ₁ -C ₆ -alkyl (e.g., cyclobutyl); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 791, 867, 868, 869, 870, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 4,7-diazaspiro[2.5]octanyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 792, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 4,7-diazaspiro[2.5]octanyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); R ² is C ₁ -C ₆ -alkyl (e.g., methyl); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 793, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2,8- dimethylimidazo[1,2-b]pyridazyl); B is bicyclic heterocyclyl (e.g., 4,7-diazaspiro[2.5]octanyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 795, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2,8- dimethylimidazo[1,2-b]pyridazyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 798, 871, 872, 873, 874, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2,8- dimethylimidazo[1,2-b]pyridazyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazyl); L ¹ and L ² are absent; Y is N; X and Z are C(R ^5a ) (e.g., -CH-); R ³ is halo (e.g., fluoro); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 799, 875, 876, 877, 878, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazyl); L ¹ and L ² are absent; Y is N; X and Z are C(R ^5a ) (e.g., -CH-); R ³ is halo (e.g., fluoro); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 800, 879, 880, 881, 882, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 4-(azetidin-1-yl)piperidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 801, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2,8- dimethylimidazo[1,2-b]pyridazyl); B is bicyclic heterocyclyl (e.g., 4,7-diazaspiro[2.5]octanyl); L ¹ and L ² are absent; Y is N; X and Z are C(R ^5a ) (e.g., -CH-); R ³ is halo (e.g., fluoro); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 804, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 4,7-diazaspiro[2.5]octanyl); L ¹ and L ² are absent; Y is N; X and Z are C(R ^5a ) (e.g., -CH-); R ³ is halo (e.g., fluoro); m is 1; and n is 0. In some embodiments, the compound of Formula (I) is Compound 805, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 5-hydroxy- 2- ethylbenzo[d]oxazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert-butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X is C(R ^5a ) (e.g., -CH-); Y and Z are N; and m and n are 0. In some embodiments, the compound of Formula (I) is Compound 808, 809, 883, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2,7- dimethyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 5-methyl-4,7-diazaspiro[2.5]octanyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 810, 811, 884 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-2- methyl-2H-indazolyl); B is bicyclic heterocyclyl (e.g., 5-methyl-4,7-diazaspiro[2.5]octanyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 812, 813, 885, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-fluoro-2- methylimidazo[1,2-a]pyridinyl); B is bicyclic heterocyclyl (e.g., 5-methyl-4,7- diazaspiro[2.5]octanyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 814, 815, 886, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-methoxy-2- methylimidazo[1,2-a]pyridyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 816, 830, 887, 888, 889, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-cyano-2- methylimidazo[1,2-a]pyridyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 817, 831, 890, 891, 892, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-chloro-2- methylimidazo[1,2-a]pyridyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 818, 893, 894, 895, 896, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-fluoro-2-methyl- [1,2,4]triazolo[1,5-a]pyridyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 819, 825, 897, 898, 899, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-fluoro- [1,2,4]triazolo[4,3-a]pyridyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 820, 833, 900, 901, 902, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2-ethyl-8- fluoroimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 821, 836, 903, 904, 905, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 3,8-difluoro-2- methylimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 822, 837, 906, 907, 908, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-methoxy-2- methylimidazo[1,2-a]pyrazinyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 823, 838, 909, 910, 911, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-fluoro-2- methylimidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., 1,2,6-trimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 824, 826, 912, 913, 914, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 2- methylimidazo[1,2-a]pyridyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 827, 832, 915, 916, 917, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-fluoro-2- (hydroxymethyl)imidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., 2,6- dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 828, 834, 918, 919, 920, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 8-fluoro-2- (fluoromethyl)imidazo[1,2-a]pyridinyl); B is monocyclic heterocyclyl (e.g., 2,6- dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 829, 835, 921, 922, 923, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 3,7-difluoro-2- methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 924, 925, 926, 927, 928, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (I), A is bicyclic heteroaryl (e.g., 6-hydroxy-7-fluoro- 2-methyl-2H-indazolyl); B is monocyclic heterocyclyl (e.g., 3-(N-(tert- butyl)amino)pyrrolidinyl); L ¹ and L ² are absent; X and Y are N; Z is C(R ^5a ) (e.g., -CH-); m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 929, 930, 931, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, the compound of Formula (II) is a compound of Formula (II-a): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; L ¹ and L ² are each independently absent, C ₁ -C ₆ -alkylene, C ₁ -C ₆ -heteroalkylene, -O-, -C(O)-, - N(R ⁴ )-, -N(R ⁴ )C(O)-, -C(O)N(R ⁴ )-, -N(R ⁴ )C(O)N(R ⁴ )-, or C ₁ -C ₆ -alkylene-N(R ⁴ )C(O)N(R ⁴ )-, wherein each alkylene and heteroalkylene is optionally substituted with one or more R ⁵ ; each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ - haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , – C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3- 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, – OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁴ is independently hydrogen, C ₁ -C ₆ -alkyl, or C ₁ -C ₆ -haloalkyl; each R ⁵ is C ₁ -C ₆ -alkyl, C ₂ -C ₆ - alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, halo, cyano, oxo, –OR ^A , or –NR ^B R ^C ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ - haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ - C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or – S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3- 7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene- heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ -C ₆ -alkyl; m and n are each independently 0, 1, or 2; and x is 0, 1, or 2. In some embodiments, the compound of Formula (II) is a compound of Formula (II-b): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; W and Z are each N or C(R ⁶ ), wherein at least one of W and Z is N; each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene- heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , – C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7- membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, – OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , , or –S(O) _x R ^D ; each R ⁶ is independently hydrogen, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , – NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or –S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene-heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ -C ₆ -alkyl; m and n are each independently 0, 1, or 2; and x is 0, 1, or 2. In some embodiments, the compound of Formula (II) is a compound of Formula (II-c): or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R ¹ ; W and Z are each N or C(R ⁶ ), wherein at least one of W and Z is N; L ^1a is absent or C ₁ - C ₆ -alkylene; each R ¹ is independently hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ - C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkenylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; or two R ¹ groups, together with the atoms to which they are attached, form a 3-7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁷ ; each R ² and R ³ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ -haloalkyl, –OR ^A , –NR ^B R ^C , –NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D ; each R ⁶ is independently hydrogen, halo, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, or –OR ^A ; each R ⁷ is independently C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -heteroalkyl, C ₁ -C ₆ - haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, –OR ^A , –NR ^B R ^C , – NR ^B C(O)R ^D , –NO ₂ , –C(O)NR ^B R ^C , –C(O)R ^D , –C(O)OR ^D , or –S(O) _x R ^D , wherein each of alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ⁸ ; each R ^A is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ - C ₆ haloalkyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, C ₁ -C ₆ alkylene-heteroaryl, –C(O)R ^D , or – S(O) _x R ^D ; each R ^B and R ^C is independently hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, cycloalkyl, heterocyclyl, or –OR ^A ; or R ^B and R ^C together with the atom to which they are attached form a 3- 7-membered heterocyclyl ring optionally substituted with one or more R ⁹ ; each R ^D is independently hydrogen, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C ₁ -C ₆ alkylene-aryl, or C ₁ -C ₆ alkylene- heteroaryl; each R ⁸ is independently C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₁ -C ₆ haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or –OR ^A ; each R ⁹ is C ₁ -C ₆ -alkyl, halo, cyano, oxo, or –OR ^A1 ; each R ^A1 is hydrogen or C ₁ -C ₆ -alkyl; m and n are each independently 0, 1, or 2; and x is 0, 1, or 2. In some embodiments, the compound of Formula (II) is selected from a compound in Table 2, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. Table 2. Exemplary compounds of Formula (II) In some embodiments, for Formula (II), A is monocyclic heteroaryl (e.g., pyrazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ is -N(R ⁴ )C(O)N(R ⁴ )- (e.g., -NHC(O)N(CH ₃ )-); L ² is absent; W and Z are N; m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 110, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (II), A is monocyclic heteroaryl (e.g., pyrazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ is -N(R ⁴ )C(O)N(R ⁴ )- (e.g., -NHC(O)NH-); L ² is absent; W and Z are N; m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 111, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In some embodiments, for Formula (II), A is monocyclic heteroaryl (e.g., pyrazolyl); B is monocyclic heterocyclyl (e.g., piperazinyl); L ¹ is C ₁ -C ₆ alkylene-N(R ⁴ )C(O)N(R ⁴ )- (e.g., - CH ₂ NHC(O)NH-); L ² is absent; W and Z are N; m is 0; and n is 0. In some embodiments, the compound of Formula (I) is Compound 112, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. Pharmaceutical Compositions, Kits, and Administration The present invention provides pharmaceutical compositions comprising a compound of Formula (I) or (II), e.g., a compound of Formula (I) or (II) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer, as described herein, and optionally a pharmaceutically acceptable excipient. In certain embodiments, the pharmaceutical composition described herein comprises a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable excipient. In certain embodiments, the compound of Formula (I) or (II) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, is provided in an effective amount in the pharmaceutical composition. In certain embodiments, the effective amount is a therapeutically effective amount. In certain embodiments, the effective amount is a prophylactically effective amount. Pharmaceutical compositions described herein can be prepared by any method known in the art of pharmacology. In general, such preparatory methods include the steps of bringing the compound of Formula (I) or (II) (the “active ingredient”) into association with a carrier and/or one or more other accessory ingredients, and then, if necessary and/or desirable, shaping and/or packaging the product into a desired single- or multi-dose unit. Pharmaceutical compositions can be prepared, packaged, and/or sold in bulk, as a single unit dose, and/or as a plurality of single unit doses. As used herein, a “unit dose” is a discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient which would be administered to a subject and/or a convenient fraction of such a dosage such as, for example, one-half or one-third of such a dosage. Relative amounts of the active ingredient, the pharmaceutically acceptable excipient, and/or any additional ingredients in a pharmaceutical composition of the invention will vary, depending upon the identity, size, and/or condition of the subject treated and further depending upon the route by which the composition is to be administered. By way of example, the composition may comprise between 0.1% and 100% (w/w) active ingredient. The term “pharmaceutically acceptable excipient” refers to a non-toxic carrier, adjuvant, diluent, or vehicle that does not destroy the pharmacological activity of the compound with which it is formulated. Pharmaceutically acceptable excipients useful in the manufacture of the pharmaceutical compositions of the invention are any of those that are well known in the art of pharmaceutical formulation and include inert diluents, dispersing and/or granulating agents, surface active agents and/or emulsifiers, disintegrating agents, binding agents, preservatives, buffering agents, lubricating agents, and/or oils. Pharmaceutically acceptable excipients useful in the manufacture of the pharmaceutical compositions of the invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat. Compositions of the present invention may be administered orally, parenterally (including subcutaneous, intramuscular, intravenous and intradermal), by inhalation spray, topically, rectally, nasally, buccally, vaginally or via an implanted reservoir. In some embodiments, provided compounds or compositions are administrable intravenously and/or orally. The term "parenteral" as used herein includes subcutaneous, intravenous, intramuscular, intraocular, intravitreal, intra-articular, intra-synovial, intrasternal, intrathecal, intrahepatic, intraperitoneal intralesional and intracranial injection or infusion techniques. Preferably, the compositions are administered orally, subcutaneously, intraperitoneally, or intravenously. Sterile injectable forms of the compositions of this invention may be aqueous or oleaginous suspension. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer’s solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. Pharmaceutically acceptable compositions of this invention may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, aqueous suspensions or solutions. In the case of tablets for oral use, carriers commonly used include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried cornstarch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening, flavoring or coloring agents may also be added. In some embodiments, a provided oral formulation is formulated for immediate release or sustained/delayed release. In some embodiments, the composition is suitable for buccal or sublingual administration, including tablets, lozenges and pastilles. A provided compound can also be in micro-encapsulated form. Alternatively, pharmaceutically acceptable compositions of this invention may be administered in the form of suppositories for rectal administration. Pharmaceutically acceptable compositions of this invention may also be administered topically, especially when the target of treatment includes areas or organs readily accessible by topical application, including diseases of the eye, the skin, or the lower intestinal tract. Suitable topical formulations are readily prepared for each of these areas or organs. For ophthalmic use, provided pharmaceutically acceptable compositions may be formulated as micronized suspensions or in an ointment such as petrolatum. In order to prolong the effect of a drug, it is often desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This can be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Although the descriptions of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions which are suitable for administration to humans, it will be understood by the skilled artisan that such compositions are generally suitable for administration to animals of all sorts. Modification of pharmaceutical compositions suitable for administration to humans in order to render the compositions suitable for administration to various animals is well understood, and the ordinarily skilled veterinary pharmacologist can design and/or perform such modification with ordinary experimentation. Compounds provided herein are typically formulated in dosage unit form, e.g., single unit dosage form, for ease of administration and uniformity of dosage. It will be understood, however, that the total daily usage of the compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular subject or organism will depend upon a variety of factors including the disease being treated and the severity of the disorder; the activity of the specific active ingredient employed; the specific composition employed; the age, body weight, general health, sex and diet of the subject; the time of administration, route of administration, and rate of excretion of the specific active ingredient employed; the duration of the treatment; drugs used in combination or coincidental with the specific active ingredient employed; and like factors well known in the medical arts. The exact amount of a compound required to achieve an effective amount will vary from subject to subject, depending, for example, on species, age, and general condition of a subject, severity of the side effects or disorder, identity of the particular compound(s), mode of administration, and the like. The desired dosage can be delivered three times a day, two times a day, once a day, every other day, every third day, every week, every two weeks, every three weeks, or every four weeks. In certain embodiments, the desired dosage can be delivered using multiple administrations (e.g., two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, or more administrations). In certain embodiments, an effective amount of a compound for administration one or more times a day to a 70 kg adult human may comprise about 0.0001 mg to about 3000 mg, about 0.0001 mg to about 2000 mg, about 0.0001 mg to about 1000 mg, about 0.001 mg to about 1000 mg, about 0.01 mg to about 1000 mg, about 0.1 mg to about 1000 mg, about 1 mg to about 1000 mg, about 1 mg to about 100 mg, about 10 mg to about 1000 mg, or about 100 mg to about 1000 mg, of a compound per unit dosage form. In certain embodiments, the compounds of Formula (I) or (II) may be at dosage levels sufficient to deliver from about 0.001 mg/kg to about 100 mg/kg, from about 0.01 mg/kg to about 50 mg/kg, preferably from about 0.1 mg/kg to about 40 mg/kg, preferably from about 0.5 mg/kg to about 30 mg/kg, from about 0.01 mg/kg to about 10 mg/kg, from about 0.1 mg/kg to about 10 mg/kg, and more preferably from about 1 mg/kg to about 25 mg/kg, of subject body weight per day, one or more times a day, to obtain the desired therapeutic effect. It will be appreciated that dose ranges as described herein provide guidance for the administration of provided pharmaceutical compositions to an adult. The amount to be administered to, for example, a child or an adolescent can be determined by a medical practitioner or person skilled in the art and can be lower or the same as that administered to an adult. It will be also appreciated that a compound or composition, as described herein, can be administered in combination with one or more additional pharmaceutical agents. The compounds or compositions can be administered in combination with additional pharmaceutical agents that improve their bioavailability, reduce and/or modify their metabolism, inhibit their excretion, and/or modify their distribution within the body. It will also be appreciated that the therapy employed may achieve a desired effect for the same disorder, and/or it may achieve different effects. The compound or composition can be administered concurrently with, prior to, or subsequent to, one or more additional pharmaceutical agents, which may be useful as, e.g., combination therapies. Pharmaceutical agents include therapeutically active agents. Pharmaceutical agents also include prophylactically active agents. Each additional pharmaceutical agent may be administered at a dose and/or on a time schedule determined for that pharmaceutical agent. The additional pharmaceutical agents may also be administered together with each other and/or with the compound or composition described herein in a single dose or administered separately in different doses. The particular combination to employ in a regimen will take into account compatibility of the inventive compound with the additional pharmaceutical agents and/or the desired therapeutic and/or prophylactic effect to be achieved. In general, it is expected that the additional pharmaceutical agents utilized in combination be utilized at levels that do not exceed the levels at which they are utilized individually. In some embodiments, the levels utilized in combination will be lower than those utilized individually. Exemplary additional pharmaceutical agents include, but are not limited to, anti-proliferative agents, anti-cancer agents, anti-diabetic agents, anti-inflammatory agents, immunosuppressant agents, and a pain-relieving agent. Pharmaceutical agents include small organic molecules such as drug compounds (e.g., compounds approved by the U.S. Food and Drug Administration as provided in the Code of Federal Regulations (CFR)), peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNAs, RNAs, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, lipids, hormones, vitamins, and cells. Also encompassed by the invention are kits (e.g., pharmaceutical packs). The inventive kits may be useful for preventing and/or treating a proliferative disease or a non-proliferative disease, e.g., as described herein. The kits provided may comprise an inventive pharmaceutical composition or compound and a container (e.g., a vial, ampule, bottle, syringe, and/or dispenser package, or other suitable container). In some embodiments, provided kits may optionally further include a second container comprising a pharmaceutical excipient for dilution or suspension of an inventive pharmaceutical composition or compound. In some embodiments, the inventive pharmaceutical composition or compound provided in the container and the second container are combined to form one-unit dosage form. Thus, in one aspect, provided are kits including a first container comprising a compound described herein, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or a pharmaceutical composition thereof. In certain embodiments, the kit of the disclosure includes a first container comprising a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In certain embodiments, the kits are useful in preventing and/or treating a disease, disorder, or condition described herein in a subject (e.g., a proliferative disease or a non-proliferative disease). In certain embodiments, the kits further include instructions for administering the compound, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or a pharmaceutical composition thereof, to a subject to prevent and/or treat a proliferative disease or a non-proliferative disease. Methods of Use Described herein are compounds useful for modulating splicing. In some embodiments, a compound of Formula (I) or (II) may be used to alter the amount, structure, or composition of a nucleic acid (e.g., a precursor RNA, e.g., a pre-mRNA, or the resulting mRNA) by increasing or decreasing splicing at a splice site. In some embodiments, increasing or decreasing splicing results in modulating the level or structure of a gene product (e.g., an RNA or protein) produced. In some embodiments, a compound of Formula (I) or (II) may modulate a component of the splicing machinery, e.g., by modulating the interaction with a component of the splicing machinery with another entity (e.g., nucleic acid, protein, or a combination thereof). The splicing machinery as referred to herein comprises one or more spliceosome components. Spliceosome components may comprise, for example, one or more of major spliceosome members (U1, U2, U4, U5, U6 snRNPs), or minor spliceosome members (U11, U12, U4atac, U6atac snRNPs) and their accessory splicing factors. In another aspect, the present disclosure features a method of modifying of a target (e.g., a precursor RNA, e.g., a pre-mRNA) through inclusion of a splice site in the target, wherein the method comprises providing a compound of Formula (I) or (II). In some embodiments, inclusion of a splice site in a target (e.g., a precursor RNA, e.g., a pre-mRNA, or the resulting mRNA) results in addition or deletion of one or more nucleic acids to the target (e.g., a new exon, e.g. a skipped exon). Addition or deletion of one or more nucleic acids to the target may result in an increase in the levels of a gene product (e.g., RNA, e.g., mRNA, or protein). In another aspect, the present disclosure features a method of modifying a target (e.g., a precursor RNA, e.g., a pre-mRNA, or the resulting mRNA) through exclusion of a splice site in the target, wherein the method comprises providing a compound of Formula (I) or (II). In some embodiments, exclusion of a splice site in a target (e.g., a precursor RNA, e.g., a pre-mRNA) results in deletion or addition of one or more nucleic acids from the target (e.g., a skipped exon, e.g. a new exon). Deletion or addition of one or more nucleic acids from the target may result in a decrease in the levels of a gene product (e.g., RNA, e.g., mRNA, or protein). In other embodiments, the methods of modifying a target (e.g., a precursor RNA, e.g., a pre-mRNA, or the resulting mRNA) comprise suppression of splicing at a splice site or enhancement of splicing at a splice site (e.g., by more than about 0.5%, e.g., 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or more), e.g., as compared to a reference (e.g., the absence of a compound of Formula (I) or (II), or in a healthy or diseased cell or tissue). The methods described herein can be used to modulate splicing, e.g., of a nucleic acid comprising a particular sequence (e.g., a target sequence). Exemplary genes encoding a target sequence (e.g., a target sequence comprising DNA or RNA, e.g., pre-mRNA) include, inter alia, ABCA4, ABCA9, ABCB1, ABCB5, ABCC9, ABCD1, ACADL, ACADM, ACADSB, ACSS2, ACTB, ACTG2, ADA, ADAL, ADAM10, ADAM15, ADAM22, ADAM32, ADAMTS12, ADAMTS13, ADAMTS20, ADAMTS6, ADAMTS9, ADAR, ADCY3, ADCY10, ADCY8, ADNP, ADRBK2, AFP, AGL, AGT, AHCTF1, AHR, AKAP10, AKAP3, AKNA, ALAS1, ALS2CL, ALB, ALDH3A2, ALG6, AMBRA1, ANK3, ANTXR2, ANXA10, ANXA11, ANGPTL3, AP2A2, AP4E1, APC, APOA1, APOB, APOC3, APOH, AR, ARID2, ARID3A, ARID3B, ARFGEF1 , ARFGEF2, ARHGAP1, ARHGAP8, ARHGAP18, ARHGAP26, ARHGEF18, ARHGEF2, ARPC3, ARS2, ASH1L, ASH1L- IT1, ASNSD1, ASPM, ATAD5, ATF1, ATG4A, ATG16L2, ATM, ATN1, ATP11C, ATP6V1G3, ATP13A5, ATP7A, ATP7B, ATR, ATXN2, ATXN3, ATXN7, ATXN10, AXIN1, B2M, B4GALNT3, BBS4, BCL2, BCL2L1, BCL2-like 11 (BIM), BCL11B, BBOX1, BCS1L, BEAN1, BHLHE40, BMPR2, BMP2K, BPTF, BRAF, BRCA1, BRCA2, BRCC3, BRSK1, BRSK2, BTAF1, BTK, C2orf55, C4orf29, C6orf118, C9orf43, C9orf72, C10orf137, C11orf30, C11orf65, C11orf70, C11οrf87, C12orf51, C13orf1, C13orf15, C14orf10l, C14orf118, C15orf29, C15orf42, C15orf60, C16orf33, C16orf38, C16orf48, C18orf8, C19orf42, C1orf107, C1orf114, C1orf130, C1orf149, C1orf27, C1orf71, C1orf94, C1R, C20orf74, C21orf70, C3orf23, C4orf18, C5orf34, C8B, C8orf33, C9orf114, C9orf86, C9orf98, C3, CA11, CAB39, CACHD1, CACNA1A, CACNA1B, CACNA1C, CACNA2D1, CACNA1G, CACNA1H, CALCA, CALCOCO2, CAMK1D, CAMKK1, CAPN3, CAPN9, CAPSL, CARD11, CARKD, CASZ1, CAT, CBLB, CBX1, CBX3, CCDC102B, CCDC11, CCDC15, CCDC18, CCDC5, CCDC81, CCDC131, CCDC146, CD4, CD274, CD1B, CDC14A, CDC16, CDC2L5, CDC42BPB, CDCA8, CDH10, CDH11, CDH24, CDH8, CDH9, CDK5RAP2, CDK6, CDK8, CDK11B, CD33, CD46, CDH1, CDH23, CDK6, CDK11B, CDK13, CEBPZ, CEL, CELSR3, CENPA, CENPI, CENPT, CENTB2, CENTG2, CEP110, CEP170, CEP192, CETP, CFB, CFTR, CFH, CGN, CGNL1, CHAF1A, CHD9, CHIC2, CHL1, CHN1, CHM, CLEC16A, CL1C2, CLCN1, CLINT1, CLK1, CLPB, CLPTM1, CMIP, CMYA5, CNGA3, CNOT1, CNOT7, CNTN6, COG3, COL11A1, COL11A2, COL12A1, COL14A1, COL15A1, COL17A1, COL19A1, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A5, COL4A6, COL5A2, COL6A1, COL7A1, COL9A1, COL9A2, COL22A1, COL24A1, COL25A1, COL29A1, COLQ, COMTD1, COPA, COPB2, COPS7B, COPZ2, CPSF2, CPXM2, CR1, CRBN, CRYZ, CREBBP, CRKRS, CSE1L, CSTB, CSTF3, CT45-6, CTNNB1, CUBN, CUL4B, CUL5, CXorf41, CXXC1, CYBB, CYFIP2, CYP3A4, CYP3A43, CYP3A5, CYP4F2, CYP4F3, CYP17, CYP19, CYP24A1, CYP27A1, DAB1, DAZ2, DCBLD1, DCC, DCTN3, DCUN1D4, DDA1, DDEF1, DDX1, DDX24, DDX4, DENND2D, DEPDC2, DES, DGAT2, DHFR, DHRS7, DHRS9, DHX8, DIP2A, DMD, DMTF1, DNAH3, DNAH8, DNAI1, DNAJA4, DNAJC13, DNAJC7, DNMT1, DNTTIP2, DOCK4, DOCK5, DOCK10, DOCK11, DOT1L, DPP3, DPP4, DPY19L2P2, DR1, DSCC1, DVL3, DUX4, DYNC1H1, DYSF, E2F1, E2F3, E2F8, E4F1, EBF1, EBF3, ECM2, EDEM3, EFCAB3, EFCAB4B, EFNA4, EFTUD2, EGFR, EIF3A, ELA1, ELA2A, ELF2, ELF3, ELF4, EMCN, EMD, EML5, ENO3, ENPP3, EP300, EPAS1, EPB41L5, EPHA3, EPHA4, EPHB1, EPHB2, EPHB3, EPS15, ERBB4, ERCC1, ERCC8, ERGIC3, ERMN, ERMP1, ERN1, ERN2, ESR1, ESRRG, ETS2, ETV3, ETV4, ETV5, ETV6, EVC2, EWSR1, EXO1, EXOC4, F3, F11, F13A1, F5, F7, F8, FAH, FAM13A1, FAM13B1, FAM13C1, FAM134A, FAM161A, FAM176B, FAM184A, FAM19A1, FAM20A, FAM23B, FAM65C, FANCA, FANCC, FANCG, FANCM, FANK1, FAR2, FBN1, FBXO15, FBXO18, FBXO38, FCGBP, FECH, FEZ2, FGA, FGD6, FGFR2, FGFR1OP, FGFR1OP2, FGFR2, FGG, FGR, FIX, FKBP3, FLI1, FLJ35848, FLJ36070, FLNA, FN1, FNBP1L, FOLH1, FOSL1, FOSL2, FOXK1, FOXM1, FOXO1, FOXP4, FRAS1, FUT9, FXN, FZD3, FZD6, GAB1, GABPA, GALC, GALNT3, GAPDH, GART, GAS2L3, GATA3, GATAD2A, GBA, GBGT1, GCG, GCGR, GCK, GFI1, GFM1, GH1, GHR, GHV, GJA1, GLA, GLT8D1, GNA11, GNAQ, GNAS, GNB5, GOLGB1, GOLT1A, GOLT1B, GPATCH1, GPR158, GPR160, GPX4, GRAMD3, GRHL1, GRHL2, GRHPR, GRIA1, GRIA3, GRIA4, GRIN2B, GRM3, GRM4, GRN, GSDMB, GSTCD, GSTO2, GTF2I, GTPBP4, HADHA, HAND2, HBA2, HBB, HCK, HDAC3, HDAC5, HDX, HEPACAM2, HERC1, HES7, HEXA, HEXB, HHEX, HIPK3, HLA-DPB1, HLA-G, HLCS, HLTF, HMBS, HMGA1, HMGCL, HNF1A, HNF1B, HNF4A, HNF4G, HNRNPH1, HOXC10, HP1BP3, HPGD, HPRT1, HPRT2, HSF1, HSF4, HSF2BP, HSPA9, HSPG2, HTT, HXA, ICA1, IDH1, IDS, IFI44L, IKBKAP, IKZF1, IKZF3, IL1R2, IL5RA, IL7RA, IMMT, INPP5D, INSR, INTS3, INTU, IP04, IP08, IQGAP2, IRF2, IRF4, IRF8, IRX3, ISL1, ISL2, ITFG1, ITGA6, ITGAL, ITGB1, ITGB2, 1TGB3, ITGB4, ITIH1, ITPR2, IWS1, JAK1, JAK2, JAG1, JMJD1C, JPH3, KALRN, KAT6A, KATNAL2, KCNN2, KCNT2, KDM2A, KIAA0256, KIAA0528, KIAA0564, KIAA0586, KIAA1033, KIAA1166, KIAA1219, KIAA1409, KIAA1622, KIAA1787, KIF3B, KIF15, KIF16B, KIF5A, KIF5B, KIF9, KIN, KIR2DL5B, KIR3DL2, KIR3DL3, KIT, KLF3, KLF5, KLF7, KLF10, KLF12, KLF16, KLHL20, KLK12, KLKB1, KMT2A, KMT2B, KPNA5, KRAS, KREMEN1, KRIT1, KRT5, KRTCAP2, KYNU, L1CAM, L3MBTL, L3MBTL2, LACE1, LAMA1, LAMA2, LAMA3, LAMB1, LARP7, LDLR, LEF1, LENG1, LGALS3, LGMN, LHCGR, LHX3, LHX6, LIMCH1, LIMK2, LIN28B, LIN54, LMBRD1, LMBRD2, LMLN, LMNA, LMO2, LMO7, LOC389634, LOC390110, LPA, LPCAT2, LPL, LRP4, LRPPRC, LRRK2, LRRC19, LRRC42, LRWD1, LUM, LVRN, LYN, LYST, MADD, MAGI1, MAGT1, MALT1, MAP2K1, MAP4K4, MAPK8IP3, MAPK9, MAPT, MARC1, MARCH5, MATN2, MBD3, MCF2L2, MCM6, MDGA2, MDM4, ASXL1, FUS, SPR54, MECOM, MEF2C, MEF2D, MEGF10, MEGF11, MEMO1, MET, MGA, MGAM, MGAT4A, MGAT5, MGC16169, MGC34774, MKKS, MIB1, MIER2, MITF, MKL2, MLANA, MLH1, MLL5, MLX, MME, MPDZ, MPI, MRAP2, MRPL11, MRPL39, MRPS28, MRPS35, MS4A13, MSH2, MSH3, MSMB, MST1R, MTDH, MTERF3, MTF1, MTF2, MTIF2, MTHFR, MUC2, MUT, MVK, MYB, MYBL2, MYC, MYCBP2, MYH2, MYRF, MYT1, MY019, MY03A, MY09B, MYOM2, MYOM3, NAG, NARG1, NARG2, NCOA1, NDC80, NDFIP2, NEB, NEDD4, NEK1, NEK5, ΝΕΚ11, NF1, NF2, NFATC2, NFE2L2, NFIA, NFIB, NFIX, NFKB1, NFKB2, NFKBIL2, NFRKB, NFYA, NFYB, NIPA2, NKAIN2, NKAP, NLRC3, NLRC5, NLRP3, NLRP7, NLRP8, NLRP13, NME1, NME1-NME2, NME2, NME7, NOL10, NOP561, NOS1, NOS2A, NOTCH1, NPAS4, NPM1, NR1D1, NR1H3, NR1H4, NR4A3, NR5A1, NRXN1, NSMAF, NSMCE2, NT5C, NT5C2, NT5C3, NUBP1, NUBPL, NUDT5, NUMA1, NUP88, NUP98, NUP160, NUPL1, OAT, OAZ1, OBFC2A, OBFC2B, OLIG2, OMA1, OPA1, OPN4, OPTN, OSBPL11, OSBPL8, OSGEPL1, OTC, OTX2, OVOL2, OXT, PA2G4, PADI4, PAH, PAN2, PAOX, PAPOLG, PARD3, PARP1, PARVB, PAWR, PAX3, PAX8, PBGD, PBRM1, PBX2, PCBP4, PCCA, PCGF2, PCNX, PCOTH, PDCD4, PDE4D, PDE8B, PDE10A, PD1A3, PDH1, PDLIM5, PDXK, PDZRN3, PELI2, PDK4, PDS5A, PDS5B, PGK1, PGM2, PHACTR4, PHEX, PHKB, PHLDB2, PHOX2B, PHTF1, PIAS1, PIEZO1, PIGF, PIGN, PIGT, PIK3C2G, PIK3CA, PIK3CD, PIK3CG, PIK3RI, PIP5K1A, PITRM1, PIWIL3, PKD1, PKHD1L1, PKD2, PKIB, PKLR, PKM1, PKM2, PLAGL2, PLCB1, PLCB4, PLCG1, PLD1, PLEKHA5, PLEKHA7, PLEKHM1, PLKR, PLXNC1, PMFBP1, POLN, POLR3D, POMT2, POSTN, POU2AF1, POU2F2, POU2F3, PPARA, PPFIA2, PPP1R12A, PPP3CB, PPP4C, PPP4R1L, PPP4R2, PRAME, PRC1, PRDM1, PREX1, PREX2, PRIM1, PRIM2, PRKAR1A, PRKCA, PRKG1, PRMT7, PROC, PROCR, PROSC, PRODH, PROX1, PRPF40B, PRPF4B, PRRG2, PRUNE2, PSD3, PSEN1, PSMAL, PTCH1, PTEN, PTK2, PTK2B, PTPN2, PTPN3, PTPN4, PTPN11, PTPN22, PTPRD, PTPRK, PTPRM, PTPRN2, PTPRT, PUS10, PVRL2, PYGM, QRSL1, RAB11FIP2, RAB23, RAF1, RALBP1, RALGDS, RB1CC1, RBL2, RBM39, RBM45, RBPJ, RBSN, REC8, RELB, RFC4, RFT1, RFTN1, RHOA, RHPN2, RIF1, RIT1, RLN3, RMND5B, RNF11, RNF32, RNFT1, RNGTT, ROCK1, ROCK2, RORA, RP1, RP6KA3, RP11- 265F1, RP13-36C9, RPAP3, RPN1, RPGR, RPL22, RPL22L1, RPS6KA6, RREB1, RRM1, RRP1B, RSK2, RTEL1, RTF1, RUFY1, RUNX1, RUNX2, RXRA, RYR3, SAAL1, SAE1, SALL4, SAT1, SATB2, SBCAD, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCNA, SCN11A, SCO1, SCYL3, SDC1, SDK1, SDK2, SEC24A, SEC24D, SEC31A, SEL1L, SENP3, SENP6, SENP7, SERPINA1, SETD3, SETD4, SETDB1, SEZ6, SFRS12, SGCE, SGOL2, SGPL1, SH2D1A, SH3BGRL2, SH3PXD2A, SH3PXD2B, SH3RF2, SH3TC2, SHOC2, SIPA1L2, SIPA1L3, SIVA1, SKAP1, SKIV2L2, SLC6A11, SLC6A13, SLC6A6, SLC7A2, SLC12A3, SLC13A1, SLC22A17, SLC25A14, SLC28A3, SLC33A1, SLC35F6, SLC38A1, SLC38A4, SLC39A10, SLC4A2, SLC6A8, SMARCA1, SMARCA2, SMARCA5, SMARCC2, SMC5, SMN2, SMOX, SMS, SMTN, SNCAIP, SNORD86, SNRK, SNRP70, SNX5, SNX6, SOD1, SOD10, SOS, SOS2, SOX5, SOX6, SOX8, SP1, SP2, SP3, SP110, SPAG9, SPATA13, SPATA4, SPATS1, SPECC1L, SPDEF, SPI1, SPINK5, SPP2, SPTA1, SRF, SRM, SRP72, SSX3, SSX5, SSX9, STAG1, STAG2, STAMBPLI, STARD6, STAT1, STAT3, STAT5A, STAT5B, STAT6, STK17B, STX3, STXBP1, SUCLG2, SULF2, SUPT6H, SUPT16H, SV2C, SYCP2, SYT6, SYCPI, SYTL3, SYTL5, TAF2, TARDBP, TBC1D3G, TBC1D8B, TBC1D26, TBC1D29, TBCEL, TBK1, TBP, TBPL1, TBR1, TBX, TCEB3, TCF3, TCF4, TCF7L2, TCFL5, TCF12, TCP11L2, TDRD3, TEAD1, TEAD3, TEAD4, TECTB, TEK, TERF1, TERF2, TET2, TFAP2A, TFAP2B, TFAP2C, TFAP4, TFDP1, TFRC, TG, TGM7, TGS1, THAP7, THAP12, THOC2, TIAL1, TIAM2, TIMM50, TLK2, TM4SF20, TM6SF1, TMEM27, TMEM77, TMEM156, TMEM194A, TMF1, TMPRSS6, TNFRSF10A, TNFRSF10B, TNFRSF8, TNK2, TNKS, TNKS2, TOM1L1, TOM1L2, TOP2B, TP53, TP53INP1, TP53BP2, TP53I3, TP63, TRAF3IP3, TRAPPC2, TRIM44, TRIM65, TRIML1, TRIML2, TRPM3, TRPM5, TRPM7, TRPS1, TSC1, TSC2, TSHB, TSPAN7, TTC17, TTF1, TTLL5, TTLL9, TTN, TTPAL, TTR, TUSC3, TXNDC10, UBE3A, UCK1, UGT1A1, UHRF1BP1, UNC45B, UNC5C, USH2A, USF2, USP1, USP6, USP18, USP38, USP39, UTP20, UTP15, UTP18, UTRN, UTX, UTY, UVRAG, UXT, VAPA, VEGFA, VPS29, VPS35, VPS39, VT11A, VT11B, VWA3B, WDFY2, WDR16, WDR17, WDR26, WDR44, WDR67, WDTC1, WRN, WRNIP1, WT1, WWC3, XBP1, XRN1, XRN2, XX-FW88277, YAP1, YARS, YBX1, YGM, YY1, ZBTB18, ZBTB20, ZC3HAV1, ZC3HC1, ZC3H7A, ZDHHC19, ZEB1, ZEB2, ZFPM1, ZFYVE1, ZFX, ZIC2, ZNF37A, ZNF91, ZNF114, ZNF155, ZNF169, ZNF205, ZNF236, ZNF317, ZNF320, ZNF326, ZNF335, ZNF365, ZNF367, ZNF407, ZNF468, ZNF506, ZNF511, ZNF511-PRAP1, ZNF519, ZNF521, ZNF592, ZNF618, ZNF763, and ZWINT. Additional exemplary genes encoding a target sequence (e.g., a target sequence comprising DNA or RNA, e.g., pre-mRNA) include genes include A1CF, A4GALT, AAR2, ABAT, ABCA11P, ZNF721, ABCA5, ABHD10, ABHD13, ABHD2, ABHD6, AC000120.3, KRIT1, AC004076.1, ZNF772, AC004076.9, ZNF772, AC004223.3, RAD51D, AC004381.6, AC006486.1, ERF, AC007390.5, AC007780.1, PRKAR1A, AC007998.2, INO80C, AC009070.1, CMC2, AC009879.2, AC009879.3, ADHFE1, AC010487.3, ZNF816-ZNF321P, ZNF816, AC010328.3, AC010522.1, ZNF587B, AC010547.4, ZNF19, AC012313.3, ZNF497, AC012651.1, CAPN3, AC013489.1, DET1, AC016747.4, C2orf74, AC020907.6, FXYD3, AC021087.5, PDCD6, AHRR, AC022137.3, ZNF761, AC025283.3, NAA60, AC027644.4, RABGEF1, AC055811.2, FLCN, AC069368.3, ANKDD1A, AC073610.3, ARF3, AC074091.1,GPN1, AC079447.1, LIPT1, AC092587.1, AC079594.2, TRIM59, AC091060.1,C18orf21, AC092143.3, MC1R, AC093227.2, ZNF607, AC093512.2, ALDOA, AC098588.1, ANAPC10, AC107871.1, CALML4, AC114490.2, ZMYM6, AC138649.1, NIPA1, AC138894.1, CLN3, AC139768.1, AC242426.2, CHD1L, ACADM, ACAP3, ACKR2,RP11- 141M3.5, KRBOX1, ACMSD, ACOT9, ACP5, ACPL2, ACSBG1, ACSF2, ACSF3, ACSL1, ACSL3, ACVR1, ADAL, ADAM29, ADAMTS10, ADAMTSL5, ADARB1, ADAT2, ADCK3, ADD3, ADGRG1, ADGRG2, ADH1B, ADIPOR1, ADNP, ADPRH, AGBL5, AGPAT1, AGPAT3, AGR2, AGTR1, AHDC1, AHI1, AHNAK, AIFM1, AIFM3, AIMP2, AK4, AKAP1, AKNAD1, CLCC1, AKR1A1, AKT1, AKT1S1, AKT2, AL139011.2, PEX19, AL157935.2, ST6GALNAC6, AL358113.1,TJP2, AL441992.2, KYAT1, AL449266.1,CLCC1, AL590556.3, LINC00339, CDC42, ALAS1, ALB, ALDH16A1, ALDH1B1, ALDH3A1, ALDH3B2, ALDOA, ALKBH2, ALPL, AMD1, AMICA1, AMN1, AMOTL2, AMY1B, AMY2B, ANAPC10, ANAPC11, ANAPC15, ANG, RNASE4, AL163636.2, ANGEL2, ANGPTL1, ANKMY1, ANKRD11, ANKRD28, ANKRD46, ANKRD9, ANKS3, ANKS3,RP11-127I20.7, ANKS6, ANKZF1, ANPEP, ANXA11, ANXA2, ANXA8L2, AL603965.1, AOC3, AP000304.12, CRYZL1, AP000311.1, CRYZL1, AP000893.2,RAB30, AP001267.5, ATP5MG, AP002495.2, AP003175.1, OR2AT4, AP003419.1, CLCF1, AP005263.1, ANKRD12, AP006621.5, AP006621.1, AP1G1, AP3M1, AP3M2, APBA2, APBB1, APLP2, APOA2, APOL1, APOL3, APTX, ARAP1,STARD10, ARF4, ARFIP1, ARFIP2, ARFRP1, ARHGAP11A, ARHGAP33, ARHGAP4, ARHGEF10, ARHGEF3, ARHGEF35, OR2A1-AS1, ARHGEF35, OR2A1-AS1, ARHGEF34P, ARID1B, ARHGEF35, OR2A20P, OR2A1-AS1, ARHGEF9, ARL1, ARL13B, ARL16, ARL6, ARMC6, ARMC8, ARMCX2, ARMCX5, RP4-769N13.6, ARMCX5-GPRASP2, BHLHB9, ARMCX5-GPRASP2,GPRASP1, ARMCX5- GPRASP2,GPRASP2, ARMCX6, ARNT2, ARPP19, ARRB2, ARSA, ART3, ASB3,GPR75-ASB3, ASCC2, ASNS, ASNS, AC079781.5, ASPSCR1, ASS1, ASUN, ATE1, ATF1, ATF7IP2, ATG13, ATG4D, ATG7, ATG9A, ATM, ATOX1, ATP1B3, ATP2C1, ATP5F1A, ATP5G2, ATP5J, ATP5MD, ATP5PF, ATP6AP2, ATP6V0B, ATP6V1C1, ATP6V1D, ATP7B, ATXN1, ATXN1L,IST1, ATXN3, ATXN7L1, AURKA, AURKB, AXDND1, B3GALNT1, B3GALT5, AF064860.1, B3GALT5,AF064860.5, B3GNT5, B4GALT3, B4GALT4, B9D1, BACH1, BAIAP2, BANF1, BANF2, BAX, BAZ2A, BBIP1, BCHE, BCL2L14, BCL6, BCL9L, BCS1L, BDH1, BDKRB2,AL355102.2, BEST1, BEST3, BEX4, BHLHB9, BID, BIN3, BIRC2, BIVM, BIVM- ERCC5, BIVM, BLCAP, BLK, BLOC1S1, RP11-644F5.10, BLOC1S6, AC090527.2, BLOC1S6, RP11-96O20.4, BLVRA, BMF, BOLA1, BORCS8-MEF2B, BORCS8, BRCA1, BRD1, BRDT, BRINP3, BROX, BTBD10, BTBD3, BTBD9, BTD, BTF3L4, BTNL9, BUB1B-PAK6, PAK6, BUB3, C10orf68, C11orf1, C11orf48, C11orf54, C11orf54,AP001273.2, C11orf57, C11orf63, C11orf82, C12orf23, C12orf4, C12orf65, C12orf79, C14orf159, C14orf93, C17orf62, C18orf21, C19orf12, C19orf40, C19orf47, C19orf48, C19orf54, C1D, C1GALT1, C1QB, C1QTNF1, C1S, C1orf101, C1orf112, C1orf116, C1orf159, C1orf63, C2, C2,CFB, C20orf27, C21orf58, C2CD4D, C2orf15, LIPT1, MRPL30, C2orf80, C2orf81, C3orf14, C3orf17, C3orf18, C3orf22, C3orf33,AC104472.3, C4orf33, C5orf28, C5orf34, C6orf118, C6orf203, C6orf211, C6orf48, C7orf50, C7orf55, C7orf55-LUC7L2, LUC7L2, C8orf44-SGK3,C8orf44, C8orf59, C9,DAB2, C9orf153, C9orf9, CA5BP1,CA5B, CABYR, CALCA, CALCOCO1, CALCOCO2, CALM1, CALM3, CALML4, RP11-315D16.2, CALN1, CALU, CANT1, CANX, CAP1, CAPN12, CAPS2, CARD8, CARHSP1, CARNS1, CASC1, CASP3, CASP7, CBFA2T2, CBS, CBY1, CCBL1, CCBL2, RBMXL1, CCDC12, CCDC126, CCDC14, CCDC149, CCDC150, CCDC169-SOHLH2, CCDC169, CCDC171, CCDC37, CCDC41, CCDC57, CCDC63, CCDC7, CCDC74B, CCDC77, CCDC82, CCDC90B, CCDC91, CCDC92, CCNE1, CCHCR1, CCL28, CCNB1IP1, CCNC, CCND3, CCNG1, CCP110, CCR9, CCT7, CCT8, CD151, CD1D, CD200, CD22, CD226, CD276, CD36, CD59, CDC26, CDC42, CDC42SE1, CDC42SE2, CDHR3, CDK10, CDK16, CDK4, CDKAL1, CDKL3,CTD-2410N18.4, CDKN1A, CDKN2A, CDNF, CEBPZOS, CELF1, CEMIP, CENPK, CEP170B, CEP250, CEP57, CEP57L1, CEP63, CERS4, CFL1, CFL2, CFLAR, CGNL1, CHCHD7, CHD1L, CHD8, CHFR,ZNF605, CHIA, CHID1, CHL1, CHM, CHMP1A, CHMP3, RNF103-CHMP3, CHRNA2, CIDEC, CIRBP, CITED1, CKLF-CMTM1, CMTM1, CKMT1B, CLDN12,CTB-13L3.1, CLDND1,AC021660.3, CLDND1,CPOX, CLHC1, CLIP1, CLUL1, CMC4, MTCP1, CNDP2, CNFN, CNOT1, CNOT6, CNOT7, CNOT8, CNR1, CNR2, CNTFR, CNTRL, COA1, COASY, COCH, COL8A1, COLCA1, COLEC11, COMMD3- BMI1, BMI1, COPS5, COPS7B, COQ8A, CORO6, COTL1, COX14,RP4-605O3.4, COX7A2, COX7A2L, COX7B2, CPA4, CPA5, CPEB1, CPNE1, AL109827.1, RBM12, CPNE1, RP1- 309K20.6, RBM12, CPNE3, CPSF3L, CPT1C, CREB3L2, CREM, CRP, CRYZ, CS,AC073896.1, CS, RP11-977G19.10, CSAD, CSDE1, CSF2RA, CSGALNACT1, CSK, CSNK2A1, CSRNP2, CT45A4, CT45A4,CT45A5, CT45A6, CTBP2, CTCFL, CTD-2116N17.1, KIAA0101, CTD- 2349B8.1, SYT17, CTD-2528L19.4, ZNF607, CTD-2619J13.8, ZNF497, CTNNA1, CTNNBIP1, CTNND1, CTPS2, CTSB, CTSL, CTTN, CUL2, CUL9, CWC15, CXorf40B, CYB561A3, CYBC1, CYLD, CYP11A1, CYP2R1, CYP4B1, CYP4F22, DAG1, DAGLB,KDELR2, DARS, DBNL, DCAF11, DCAF8,PEX19, DCLRE1C, DCTD, DCTN1, DCTN4, DCUN1D2, DDR1, DDX11, DDX19B, AC012184.2, DDX19B, RP11-529K1.3, DDX25, DDX39B, ATP6V1G2-DDX39B, SNORD84, DDX42, DDX60L, DEDD, DEDD2, DEFA1, DEFA1B, DEFA1B, DEFA3, DENND1C, DENND2A, DENND4B, DET1, DGKA, DGKZ, DGLUCY, DHRS4L2, DHRS9, DHX40, DIABLO, AC048338.1, DIAPH1, DICER1, DKKL1, DLG1, DLG3, DLST, DMC1, DMKN, DMTF1, DMTN, DNAJC14, DNAJC19, DNAL1, DNASE1L1, DNMT3A, DOC2A, DOCK8, DOK1, DOPEY1, DPAGT1, DPP8, DRAM2, DRD2, DROSHA, DSN1, DTNA, DTX2, DTX3, DUOX1, DUOXA1, DUS2, DUSP10, DUSP13, DUSP18, DUSP22, DYDC1, DYDC2, DYNLL1, DYNLT1, DYRK1A, DYRK2, DYRK4, RP11-500M8.7, DZIP1L, E2F6, ECHDC1, ECSIT, ECT2, EDC3, EDEM1, EDEM2, MMP24-AS1, RP4-614O4.11, EEF1AKNMT, EEF1D, EFEMP1, EFHC1, EGFL7, EHF, EI24, EIF1AD, EIF2B5, EIF4G1, EIF2B5, POLR2H, EIF3E, EIF3K, EIF4E3, EIF4G1, ELF1, ELMO2, ELMOD1, AP000889.3, ELMOD3, ELOC, ELOF1, ELOVL1, ELOVL7, ELP1, ELP6, EML3, EMP3, ENC1, ENDOV, ENO1, ENPP5, ENTHD2, ENTPD6, EP400NL, EPB41L1, EPDR1,NME8, EPHX1, EPM2A, EPN1, EPN2, EPN3, EPS8L2, ERBB3, ERC1, ERCC1, ERG, ERI2, ERI2, DCUN1D3, ERLIN2, ERMARD, ERRFI1, ESR2,RP11-544I20.2, ESRRA, ESRRB, ESRRG, ETFA, ETFRF1, ETV1, ETV4, ETV7, EVA1A, EVC2, EVX1, EXD2, EXO5, EXOC1, EXOC2, FAAP24, FABP6, FADS1, FADS2, FAHD2B, FAM107B, FAM111A, FAM111B, FAM114A1, FAM114A2, FAM115C, FAM115C,FAM115D, FAM120B, FAM133B, FAM135A, FAM153A, FAM153B, FAM154B, FAM156A, FAM156B, FAM168B, FAM172A, FAM182B, FAM192A, FAM19A2, FAM200B, FAM220A, FAM220A, AC009412.1, FAM222B, FAM227B, FAM234A, AC004754.1, FAM3C, FAM45A, FAM49B, FAM60A, FAM63A, FAM81A, FAM86B1, FAM86B2, FANCI, FANK1, FAR2, FAXC, FAXDC2, FBF1, FBH1, FBXL4, FBXO18, FBXO22, FBXO31, FBXO41, FBXO44, FBXO45, FBXW9, FCHO1, FCHSD2, FDFT1, FDPS, FER, FETUB, FGD4, FGF1, FGFR1, FGFRL1, FGL1, FHL2, FIBCD1, FIGNL1, FIGNL1,DDC, FKBP5, FKRP, FLRT2, FLRT3, FMC1, LUC7L2, FMC1-LUC7L2, FNDC3B, FOLH1, FOLR1, FOXP1, FOXK1, FOXM1, FOXO1, FOXP4, AC097634.4, FOXRED1, FPR1, FPR2, FRG1B, FRS2, FTO, FTSJ1, FUK, FUT10, FUT3, FUT6, FXYD3, FZD3, G2E3, GAA, GABARAPL1, GABPB1, GABRA5, GAL3ST1, GALE, GALNT11, GALNT14, GALNT6, GAPVD1, GARNL3, GAS2L3, GAS8, GATA1, GATA2, GATA4, GBA, GCNT1, GDPD2, GDPD5, GEMIN7,MARK4, GEMIN8, GGA3, GGACT, AL356966.1, GGPS1, GHRL, GID8, GIGYF2, GIMAP8, GIPC1, GJB1, GJB6, GLB1L, GLI1, GLT8D1, GMFG, GMPR2, GNAI2, GNAQ,GNB1, GNB2, GNE, GNG2, GNGT2, GNPDA1, GNPDA2, GOLGA3,CHFR, GOLGA4, GOLPH3L, GOLT1B, GPBP1L1, GPER1, GPR116, GPR141,EPDR1, GPR155, GPR161, GPR56, GPR63, GPR75-ASB3,ASB3, GPR85, GPSM2, GRAMD1B, GRB10, GRB7, GREM2, GRIA2, GSDMB, GSE1, GSN, GSTA4, GSTZ1, GTDC1, GTF2H1, GTF2H4, VARS2, GTF3C2, GUCY1A3, GUCY1B3, GUK1, GULP1, GYPC, GYS1, GZF1, HAGH, HAO2, HAPLN3, HAVCR1, HAX1, HBG2, AC104389.4, HBG2, AC104389.4, HBE1, HBG2, AC104389.4, HBE1,OR51B5, HBG2,HBE1, AC104389.28, HBS1L, HCFC1R1, HCK, HDAC2, HDAC6, HDAC7, HDLBP, HEATR4, HECTD4, HEXIM2, HHAT, HHATL, CCDC13, HINFP, HIRA, C22orf39, HIVEP3, HJV, HKR1, HLF, HMBOX1, HMGA1, HMGB3, HMGCR, HMGN4, HMOX2, HNRNPC, HNRNPD, HNRNPH1, HNRNPH3, HNRNPR, HOMER3, HOPX, HOXA3, HOXB3, HOXB3,HOXB4, HOXC4, HOXD3, HOXD3,HOXD4, HPCAL1, HPS4, HPS5, HRH1, HS3ST3A1, HSH2D, HSP90AA1, HSPD1, HTT, HUWE1, HYOU1, IAH1, ICA1L, ICAM2, ICE2, ICK, IDH2, IDH3G, IDS, IFI27, IFI44, IFT20, IFT22, IFT88, IGF2, INS-IGF2, IGF2BP3, IGFBP6, IKBKAP, IKBKB, IL11, IL18BP, IL18RAP, IL1RAP, IL1RL1, IL18R1, IL1RN, IL32, IL4I1,NUP62,AC011452.1, IL4I1,NUP62,CTC- 326K19.6, IL6ST, ILVBL, IMMP1L, IMPDH1, INCA1, ING1, INIP, INPP1, INPP5J, INPP5K, INSIG2, INTS11, INTS12, INTS14, IP6K2, IP6K3, IPO11, LRRC70, IQCE, IQGAP3, IRAK4, IRF3, IRF5, IRF6, ISG20, IST1, ISYNA1, ITFG2, ITGB1BP1, ITGB7, ITIH4, RP5-966M1.6, ITPRIPL1, JADE1, JAK2, JARID2, JDP2, KANK1, KANK1,RP11-31F19.1, KANK2, KANSL1L, KAT6A, KBTBD2, KBTBD3, KCNAB2, KCNE3, KCNG1, KCNJ16, KCNJ9, KCNMB2,AC117457.1,LINC01014, KCTD20, KCTD7,RABGEF1, KDM1B, KDM4A,AL451062.3, KHNYN, KIAA0040, KIAA0125, KIAA0196, KIAA0226L, PPP1R2P4, KIAA0391, KIAA0391, AL121594.1, KIAA0391, PSMA6, KIAA0753, KIAA0895, KIAA0895L, KIAA1191, KIAA1407, KIAA1841, C2orf74, KIF12, KIF14, KIF27, KIF9, KIFC3, KIN, KIRREL1, KITLG, KLC1, APOPT1, AL139300.1, KLC4, KLHDC4, KLHDC8A, KLHL13, KLHL18, KLHL2, KLHL24, KLHL7, KLK11, KLK2, KLK5, KLK6, KLK7, KNOP1, KRBA2, AC135178.2, KRBA2, RP11-849F2.7, KRIT1, KRT15, KRT8, KTN1, KXD1, KYAT3, RBMXL1, KYNU, L3MBTL1, LACC1, LARGE, LARP4, LARP7, LAT2, LBHD1, LCA5, LCA5L, LCTL, LEPROTL1, LGALS8, LGALS9C, LGMN, LHFPL2, LIG4, LIMCH1, LIMK2, LIMS2, LINC00921, ZNF263, LIPF, LLGL2, LMAN2L, LMCD1, LMF1, RP11-161M6.2, LMO1, LMO3, LOXHD1, LPAR1, LPAR2, LPAR4, LPAR5, LPAR6, LPHN1, LPIN2, LPIN3, LPP, LRFN5, LRIF1, LRMP, LRRC14, LRRC20, LRRC24, C8orf82, LRRC39, LRRC42, LRRC48, LRRC4C, LRRC8A, LRRC8B, LRRD1, LRTOMT, LRTOMT, AP000812.5, LSM7, LTB4R, LTBP3, LUC7L2, FMC1-LUC7L2, LUC7L3, LUZP1, LYG1, LYL1, LYPD4, LYPD6B, LYRM1, LYRM5, LYSMD4, MACC1, MAD1L1, MAD1L1, AC069288.1, MAEA, MAFF, MAFG, MAFK, MAGEA12,CSAG4, MAGEA2, MAGEA2B, MAGEA4, MAGEB1, MAGOHB, MAN2A2, MANBAL, MAOB, MAP2K3, MAP3K7CL, MAP3K8, MAP7, MAP9, MAPK6, MAPK7, MAPK8, MAPKAP1, 10-Mar, 7-Mar, 8-Mar, MARK2, MASP1, MATK, MATR3, MATR3,SNHG4, MB, MBD5, MBNL1, MBOAT7, MCC, MCFD2, MCM9, MCOLN3, MCRS1, MDC1, MDGA2, MDH2, MDM2, ME1, MEAK7, MECR, MED4, MEF2A, MEF2B,BORCS8-MEF2B, MEF2BNB- MEF2B, MEF2B, MEF2BNB, MEF2C, MEF2D, MEGF10, MEI1, MEIS2, MELK, MET, METTL13, METTL23, MFF, MFN2, MFSD2A, MGST3, MIB2, MICAL1, MICAL3, MICOS10, NBL1,MICOS10-NBL1, MID1, MINA, MINOS1-NBL1,MINOS1, MIOS, MIPOL1, MIS12, MKLN1, MKNK1, MKNK1,MOB3C, MLF2, MLH1, MMP17, MOBP, MOCS1, MOGS, MOK, MORF4L1, MPC1, MPC2, MPG, MPI, MPP1, MPP2, MPPE1, MPST, MRAS, MRO, MROH1, MROH7-TTC4, MROH7, MRPL14, MRPL24, MRPL33,BABAM2, MRPL33, BRE, MRPL47, MRPL48, MRPL55, MRRF, MRTFA, MRTFB, MRVI1, MS4A1, MS4A15, MS4A3, MS4A6E,MS4A7,MS4A14, MSANTD3, MSANTD4, MSH5,MSH5-SAPCD1, MSL2, MSRB3, MSS51, MTCP1,CMC4, MTERF, MTERF1, MTERF3, MTERFD2, MTERFD3, MTF2, MTG2, MTHFD2, MTHFD2L, MTIF2, MTIF3, MTMR10, MTRF1, MTRR, MTUS2, MUTYH, MVK, MX1, MX2, MYH10, MYL12A, MYB, MYD88, MYL5, MYLIP, MYNN, MYO15A, MYO1B, MYOM2, MZF1, N4BP2L2, NAA60, NAB1, NAE1, NAGK, NAP1L1, NAP1L4, NAPG, NARFL, NARG2, NAT1, NAT10, NBPF11, WI2-3658N16.1, NBPF12, NBPF15, NBPF24, NBPF6, NBPF9, NBR1, NCAPG2, NCBP2, NCEH1, NCOA1, NCOA4, NDC1, NDRG1, NDRG2, NDRG4, NDST1, NDUFAF6, NDUFB2, NDUFC1, NDUFS1, NDUFS8, NDUFV1, NEDD1, NEIL1, NEIL2, NEK10, NEK11, NEK6, NEK9, NELFA, NEU4, NFAT5, NFE2, NFE2L2, AC019080.1, NFRKB, NFYA, NFYC, NIF3L1, NIPA2, NKIRAS1, NKX2-1, NLRC3, NME1,NME1-NME2,NME2, NME1-NME2, NME2, NME4, NME6, NME9, NOD1, NOL10, NOL8, NONO, NPAS1, NPIPA8, RP11-1212A22.1, NPIPB3, NPIPB4, NPIPB9, NPL, NPM1, NPPA, NQO2, NR1H3, NR2C2, NR2F2, NR4A1, NRDC, NREP, NRF1, NRG4, NRIP1, NSD2, NSDHL, NSG1, NSMCE2, NSRP1, NT5C2, NTF4, NTMT1, NTNG2, NUBP2, NUCB2, NUDT1, NUDT2, NUDT4, NUF2, NUMBL, NUP50, NUP54, NUP85, NVL, NXF1, NXPE1, NXPE3, OARD1, OAT, OAZ2, OCIAD1, OCLN, ODF2, OGDHL, OGFOD2, AC026362.1, OGFOD2, RP11-197N18.2, OLA1, OPRL1, OPTN, OR2H1, ORAI2, ORMDL1, ORMDL2, ORMDL3, OSBPL2, OSBPL3, OSBPL5, OSBPL9, OSER1, OSGIN1, OSR2, P2RX4, P2RY2, P2RY6, P4HA2, PABPC1, PACRGL, PACSIN3, PADI1, PAIP2, PAK1, PAK3, PAK4, PAK7, PALB2, PANK2, PAQR6, PARP11, PARVG, PASK, PAX6, PBRM1, PBXIP1, PCBP3, PCBP4,AC115284.1, PCBP4, RP11-155D18.14, RP11-155D18.12, PCGF3, PCGF5, PCNP, PCSK9, PDCD10, PDCD6, AHRR, PDDC1, PDGFRB, PDIA6, PDIK1L, PDLIM7, PDP1, PDPK1, PDPN, PDZD11, PEA15, PEX2, PEX5, PEX5L, PFKM, PFN4, PGAP2, PGAP2, AC090587.2, PGAP3, PGM3, PGPEP1, PHB, PHC2, PHF20, PHF21A, PHF23, PHKB, PHLDB1, PHOSPHO1, PHOSPHO2, KLHL23, PI4KB, PIAS2, PICALM, PIF1, PIGN, PIGO, PIGT, PIK3CD, PILRB, STAG3L5P-PVRIG2P-PILRB, PIP5K1B, PIR, PISD, PIWIL4,FUT4, PKD2, PKIA, PKIG, PKM, PKN2, PLA1A, PLA2G2A, PLA2G5, PLA2G7, PLAC8, PLAGL1, PLD1, PLD3, PLEKHA1, PLEKHA2, PLEKHA6, PLEKHG5, PLIN1, PLS1, PLS3, PLSCR1, PLSCR2, PLSCR4, PLXNB1, PLXNB2, PMP22, PMS1, PNISR, PNKP,AKT1S1, PNMT, PNPLA4, PNPLA8, PNPO, PNRC1, POC1B, POFUT1, POLB, POLD1, POLH, POLI, POLL, POLR1B, POM121, POM121C,AC006014.7, POM121C, AC211429.1, POMC, POMT1, POP1, PORCN, POU5F1, PSORS1C3, PPARD, PPARG, PPHLN1, PPIL3, PPIL4, PPM1A, PPM1B,AC013717.1, PPP1CB, PPP1R11, PPP1R13L, PPP1R26, PPP1R9A, PPP2R2B, PPP3CA, PPP6R1, PPP6R3, PPT2,PPT2-EGFL8, EGFL8, PPWD1, PRDM2, PRDM8, PRELID3A, PREPL, PRICKLE1, PRKAG1, PRMT2, PRMT5, PRMT7, PROM1, PRPS1, PRPSAP2, PRR14L, PRR15L, PRR5,PRR5-ARHGAP8, PRR5L, PRR7, PRRC2B, PRRT4, PRSS50, PRSS45, PRSS44, PRUNE, PRUNE1, PSEN1, PSMA2, PSMF1, PSORS1C1, PSPH, PSRC1, PTBP3, PTHLH, PTK2, PTPDC1, PTPRM, PUF60, PUM2, PUS1, PUS10, PXN, PXYLP1, PYCR1, QRICH1, R3HCC1L, R3HDM2, RAB17, RAB23, RAB3A, RAB3D,TMEM205, RAB4B-EGLN2, EGLN2, AC008537.1, RAB5B, RAB7L1, RABL2A, RABL2B, RABL5, RACGAP1, RAD17, RAD51L3-RFFL, RAD51D, RAD52, RAE1, RAI14, RAI2, RALBP1, RAN, RANGAP1, RAP1A, RAP1B, RAP1GAP, RAPGEF4, RAPGEFL1, RASGRP2, RASSF1, RBCK1, RBM12B, RBM14, RBM4, RBM14-RBM4, RBM23, RBM4, RBM14-RBM4, RBM47, RBM7,AP002373.1, RBM7, RP11-212D19.4, RBMS2, RBMY1E, RBPJ, RBPMS, RBSN, RCBTB2, RCC1, RCC1, SNHG3, RCCD1, RECQL, RELL2, REPIN1, AC073111.3, REPIN1, ZNF775, RER1, RERE, RFWD3, RFX3, RGL2, RGMB, RGS11, RGS3, RGS5, AL592435.1, RHBDD1, RHNO1, TULP3, RHOC, AL603832.3, RHOC,RP11-426L16.10, RHOH, RIC8B, RIMKLB, RIN1, RIPK2, RIT1, RLIM, RNASE4,ANG,AL163636.6, RNASEK, RNASEK-C17orf49, RNF111, RNF123, RNF13, RNF14, RNF185, RNF216, RNF24, RNF32, RNF34, RNF38, RNF4, RNF44, RNH1, RNMT, RNPS1, RO60, ROPN1, ROPN1B, ROR2, RP1-102H19.8, C6orf163, RP1-283E3.8,CDK11A, RP11-120M18.2,PRKAR1A, RP11-133K1.2, PAK6, RP11- 164J13.1,CAPN3, RP11-21J18.1, ANKRD12, RP11-322E11.6,INO80C, RP11- 337C18.10,CHD1L, RP11-432B6.3, TRIM59, RP11-468E2.4,IRF9, RP11-484M3.5,UPK1B, RP11-517H2.6, CCR6, RP11-613M10.9, SLC25A51, RP11-659G9.3, RAB30, RP11- 691N7.6,CTNND1, RP11-849H4.2, RP11-896J10.3, NKX2-1, RP11-96O20.4,SQRDL, RP11- 986E7.7, SERPINA3, RP4-769N13.6, GPRASP1, RP4-769N13.6,GPRASP2, RP4-798P15.3, SEC16B, RP5-1021I20.4, ZNF410, RP6-109B7.3, FLJ27365, RPE, RPH3AL, RPL15, RPL17, RPL17-C18orf32,RPL17, RPL23A, RPL36,HSD11B1L, RPP38, RPS20, RPS27A, RPS3A, RPS6KA3, RPS6KC1, RPS6KL1, RPUSD1, RRAGD, RRAS2, RRBP1, RSL1D1, RSRC2, RSRP1, RUBCNL, RUNX1T1, RUVBL2, RWDD1, RWDD4, S100A13,AL162258.1, S100A13,RP1- 178F15.5, S100A16, S100A4, S100A3, S100A6, S100PBP, SAA1, SACM1L, SAMD4B, SAR1A, SARAF, SARNP,RP11-762I7.5, SCAMP5, SCAP, SCAPER, SCFD1, SCGB3A2, SCIN, SCML1, SCNN1D, SCO2, SCOC, SCRN1, SDC2, SDC4, SEC13, SEC14L1, SEC14L2, SEC22C, SEC23B, SEC24C, SEC61G, SEMA4A, SEMA4C, SEMA4D, SEMA6C, SENP7, SEPP1, 11-Sep, 2-Sep, SERGEF, AC055860.1, SERP1, SERPINA1, SERPINA5, SERPINB6, SERPING1, SERPINH1, SERTAD3, SETD5, SFMBT1, AC096887.1, SFTPA1, SFTPA2, SFXN2, SGCD, SGCE, SGK3, SGK3,C8orf44, SH2B1, SH2D6, SH3BP1,Z83844.3, SH3BP2, SH3BP5, SH3D19, SH3YL1, SHC1, SHISA5, SHMT1, SHMT2, SHOC2, SHROOM1, SIGLEC5,SIGLEC14, SIL1, SIN3A, SIRT2, SIRT6, SKP1, STAT4, AC104109.3, SLAIN1, SLC10A3, SLC12A9, SLC14A1, SLC16A6, SLC1A2, SLC1A6, SLC20A2, SLC25A18, SLC25A19, SLC25A22, SLC25A25, SLC25A29, SLC25A30, SLC25A32, SLC25A39, SLC25A44, SLC25A45, SLC25A53, SLC26A11, SLC26A4, SLC28A1, SLC29A1, SLC2A14, SLC2A5, SLC2A8, SLC35B2, SLC35B3, SLC35C2, SLC37A1, SLC38A1, SLC38A11, SLC39A13, SLC39A14, SLC41A3, SLC44A3, SLC4A7, SLC4A8, SLC5A10, SLC5A11, SLC6A1, SLC6A12, SLC6A9, SLC7A2, SLC7A6, SLC7A7, SLCO1A2, SLCO1C1, SLCO2B1, SLFN11, SLFN12, SLFNL1, SLMO1, SLTM, SLU7, SMAD2, SMAP2, SMARCA2, SMARCE1, AC073508.2, SMARCE1, KRT222, SMC6, SMG7, SMIM22, SMOX, SMPDL3A, SMTN, SMU1, SMUG1, SNAP25, SNCA, SNRK, SNRPC, SNRPD1, SNRPD2, SNRPN, SNRPN,SNURF, SNUPN, SNX11, SNX16, SNX17, SOAT1, SOHLH2,CCDC169- SOHLH2,CCDC169, SORBS1, SORBS2, SOX5, SP2, SPART, SPATA20, SPATA21, SPATS2, SPATS2L, SPDYE2, SPECC1, SPECC1L,SPECC1L-ADORA2A, SPECC1L-ADORA2A, ADORA2A, SPEG, SPG20, SPG21, SPIDR, SPIN1, SPOCD1, SPOP, SPRR2A, SPRR2B, SPRR2E, SPRR2B, SPRR2F, SPRR2D, SPRR3, SPRY1, SPRY4, SPTBN2, SRC, SRGAP1, SRP68, SRSF11, SSX1, SSX2IP, ST3GAL4, ST3GAL6, ST5, ST6GALNAC6, ST7L, STAC3, STAG1, STAG2, STAMBP, STAMBPL1, STARD3NL, STAT6, STAU1, STAU2, AC022826.2, STAU2, RP11-463D19.2, STEAP2, STEAP3, STIL, STK25, STK33, STK38L, STK40, STMN1, STON1,STON1-GTF2A1L, STRAP, STRBP, STRC, AC011330.5, STRC, CATSPER2, STRC, CATSPER2, AC011330.5, STRC,STRCP1, STT3A, STX16-NPEPL1, NPEPL1, STX5, STX6, STX8, STXBP6, STYK1, SULT1A1, SULT1A2, SUMF2, SUN1, SUN2, SUN2, DNAL4, SUOX, SUPT6H, SUV39H2, SV2B, SYBU, SYNCRIP, SYNJ2, SYT1, SYTL4, TAB2, TACC1, TADA2B, TAF1C, TAF6,AC073842.2, TAF6, RP11-506M12.1, TAF9, TAGLN, TANK, TAPSAR1,PSMB9, TAPT1, TATDN1, TAZ, TBC1D1, TBC1D12, HELLS, TBC1D15, TBC1D3H,TBC1D3G, TBC1D5, TBC1D5,SATB1, TBCA, TBCEL, TBCEL, AP000646.1, TBL1XR1, TBP, TBX5, TBXAS1, TCAF1, TCEA2, TCEAL4, TCEAL8, TCEAL9, TCEANC, TCEB1, TCF19, TCF25, TCF4, TCP1, TCP10L, AP000275.65, TCP11, TCP11L2, TCTN1, TDG, TDP1, TDRD7, TEAD2, TECR, TENC1, TENT4A, TEX264, TEX30, TEX37, TFDP1, TFDP2, TFEB, TFG, TFP1,TF, TFPI, TGIF1, THAP6, THBS3, THOC5, THRAP3, THUMPD3, TIAL1, TIMM9, TIMP1, TIRAP, TJAP1, TJP2, TK2, TLDC1, TLE3, TLE6, TLN1, TLR10, TM9SF1, TMBIM1, TMBIM4, TMBIM6, TMC6, TMCC1, TMCO4, TMEM126A, TMEM139, TMEM150B, TMEM155, TMEM161B, TMEM164, TMEM168, TMEM169, TMEM175, TMEM176B, TMEM182, TMEM199,CTB-96E2.3, TMEM216, TMEM218, TMEM230, TMEM263, TMEM45A, TMEM45B, TMEM62, TMEM63B, TMEM66, TMEM68, TMEM98, TMEM9B, TMPRSS11D, TMPRSS5, TMSB15B, TMTC4, TMUB2, TMX2-CTNND1, RP11-691N7.6,CTNND1, TNFAIP2, TNFAIP8L2, SCNM1, TNFRSF10C, TNFRSF19, TNFRSF8, TNFSF12-TNFSF13, TNFSF12, TNFSF13, TNFSF12-TNFSF13, TNFSF13, TNIP1, TNK2, TNNT1, TNRC18, TNS3, TOB2, TOM1L1, TOP1MT, TOP3B, TOX2, TP53,RP11-199F11.2, TP53I11, TP53INP2, TPCN1, TPM3P9,AC022137.3, TPT1, TRA2B, TRAF2, TRAF3, TRAPPC12, TRAPPC3, TREH, TREX1, TREX2, TRIB2, TRIM3, TRIM36, TRIM39, TRIM46, TRIM6, TRIM6-TRIM34, TRIM6-TRIM34, TRIM34, TRIM66, TRIM73, TRIT1, TRMT10B, TRMT2B, TRMT2B-AS1, TRNT1, TRO, TROVE2, TRPS1, TRPT1, TSC2, TSGA10, TSPAN14, TSPAN3, TSPAN4, TSPAN5, TSPAN6, TSPAN9, TSPO, TTC12, TTC23, TTC3, TTC39A, TTC39C, TTLL1, TTLL7, TTPAL, TUBD1, TWNK, TXNL4A, TXNL4B, TXNRD1, TYK2, U2AF1, UBA2, UBA52, UBAP2, UBE2D2, UBE2D3, UBE2E3, UBE2I, UBE2J2, UBE3A, UBL7, UBXN11, UBXN7, UGDH, UGGT1, UGP2, UMAD1,AC007161.3, UNC45A, UQCC1, URGCP-MRPS24,URGCP, USMG5, USP16, USP21, USP28, USP3, USP33, USP35, USP54, USP9Y, USPL1, UTP15, VARS2, VASH2, VAV3, VDAC1, VDAC2, VDR, VEZT, VGF, VIL1, VILL, VIPR1, VPS29, VPS37C, VPS8, VPS9D1, VRK2, VWA1, VWA5A, WARS, WASF1, WASHC5, WBP5, WDHD1, WDPCP, WDR37, WDR53, WDR6, WDR72, WDR74, WDR81, WDR86, WDYHV1, WFDC3, WHSC1, WIPF1, WSCD2, WWP2, XAGE1A, XAGE1B, XKR9, XPNPEP1, XRCC3, XRN2, XXYLT1, YIF1A, YIF1B, YIPF1, YIPF5, YPEL5, YWHAB, YWHAZ, YY1AP1, ZBTB1, ZBTB14, ZBTB18, ZBTB20, ZBTB21, ZBTB25, ZBTB33, ZBTB34, ZBTB38, ZBTB43, ZBTB49, ZBTB7B, ZBTB7C, ZBTB8OS, ZC3H11A, ZBED6, ZC3H13, ZCCHC17, ZCCHC7, ZDHHC11, ZDHHC13, ZEB2, ZFAND5, ZFAND6, ZFP1, ZFP62, ZFX, ZFYVE16, ZFYVE19, ZFYVE20, ZFYVE27, ZHX2, AC016405.1, ZHX3, ZIK1, ZIM2,PEG3, ZKSCAN1, ZKSCAN3, ZKSCAN8, ZMAT3, ZMAT5, ZMIZ2, ZMYM6, ZMYND11, ZNF10,AC026786.1, ZNF133, ZNF146, ZNF16, ZNF177, ZNF18, ZNF200, ZNF202, ZNF211, ZNF219, ZNF226, ZNF227, ZNF23, AC010547.4, ZNF23, AC010547.9, ZNF239, ZNF248, ZNF25, ZNF253, ZNF254, ZNF254, AC092279.1, ZNF263, ZNF274, ZNF275, ZNF28,ZNF468, ZNF283, ZNF287, ZNF3, ZNF320, ZNF322, ZNF324B, ZNF331, ZNF334, ZNF34, ZNF350, ZNF385A, ZNF395, FBXO16, ZNF415, ZNF418, ZNF43, ZNF433-AS1, AC008770.4, ZNF438, ZNF444, ZNF445, ZNF467, ZNF480, ZNF493, ZNF493,CTD-2561J22.3, ZNF502, ZNF507, ZNF512, AC074091.1, ZNF512,RP11-158I13.2, ZNF512B, ZNF512B, SAMD10, ZNF521, ZNF532, ZNF544, AC020915.5, ZNF544, CTD- 3138B18.4, ZNF559,ZNF177, ZNF562, ZNF567, ZNF569, ZNF570, ZNF571-AS1,ZNF540, ZNF577, ZNF580,ZNF581, ZNF580, ZNF581,CCDC106, ZNF600, ZNF611, ZNF613, ZNF615, ZNF619,ZNF620, ZNF639, ZNF652, ZNF665, ZNF667, ZNF668, ZNF671, ZNF682, ZNF687, ZNF691, ZNF696, ZNF701, ZNF706, ZNF707, ZNF714, ZNF717, ZNF718, ZNF720, ZNF721, ZNF730, ZNF763, ZNF780B, AC005614.5, ZNF782, ZNF786, ZNF79, ZNF791, ZNF81, ZNF83, ZNF837, ZNF839, ZNF84, ZNF845, ZNF846, ZNF865, ZNF91, ZNF92, ZNHIT3, ZSCAN21, ZSCAN25, ZSCAN30, and ZSCAN32. In some embodiments, the gene encoding a target sequence comprises the HTT gene. In some embodiments, the gene encoding a target sequence comprises the MYB gene. In some embodiments, the gene encoding a target sequence comprises the SMN2 gene. In some embodiments, the gene encoding a target sequence comprises the FOXM1 gene. Exemplary genes that may be modulated by the compounds of Formula (I) or (II) described herein may also include, inter alia, AC005258.1, AC005943.1, AC007849.1, AC008770.2, AC010487.3, AC011477.4, AC012651.1, AC012531.3, AC034102.2, AC073896.4, AC ₁ 04472.3, AL109811.3, AL133342.1, AL137782.1, AL157871.5, AF241726.2, AL355336.1, AL358113.1, AL360181.3, AL445423.2, AL691482.3, AP001267.5, RF01169, and RF02271. The compounds described herein may further be used to modulate a sequence comprising a particular splice site sequence, e.g., an RNA sequence (e.g., a pre-mRNA sequence). In some embodiments, the splice site sequence comprises a 5’ splice site sequence. In some embodiments, the splice site sequence comprises a 3’ splice site sequence. Exemplary gene sequences and splice site sequences (e.g., 5’ splice site sequences) include AAAgcaaguu (SEQ ID NO: 1), AAAguaaaaa (SEQ ID NO: 2), AAAguaaaau (SEQ ID NO: 3), AAAguaaagu (SEQ ID NO: 4), AAAguaaaua (SEQ ID NO: 5), AAAguaaaug (SEQ ID NO: 6), AAAguaaauu (SEQ ID NO: 7), AAAguaacac (SEQ ID NO: 8), AAAguaacca (SEQ ID NO: 9), AAAguaacuu (SEQ ID NO: 10), AAAguaagaa (SEQ ID NO: 11), AAAguaagac (SEQ ID NO: 12), AAAguaagag (SEQ ID NO: 13), AAAguaagau (SEQ ID NO: 14), AAAguaagca (SEQ ID NO: 15), AAAguaagcc (SEQ ID NO: 16), AAAguaagcu (SEQ ID NO: 17), AAAguaagga (SEQ ID NO: 18), AAAguaaggg (SEQ ID NO: 19), AAAguaaggu (SEQ ID NO: 20), AAAguaagua (SEQ ID NO: 21), AAAguaaguc (SEQ ID NO: 22), AAAguaagug (SEQ ID NO: 23), AAAguaaguu (SEQ ID NO: 24), AAAguaaucu (SEQ ID NO: 25), AAAguaauua (SEQ ID NO: 26), AAAguacaaa (SEQ ID NO: 27), AAAguaccgg (SEQ ID NO: 28), AAAguacuag (SEQ ID NO: 29), AAAguacugg (SEQ ID NO: 30), AAAguacuuc (SEQ ID NO: 31), AAAguacuug (SEQ ID NO: 32), AAAguagcuu (SEQ ID NO: 33), AAAguaggag (SEQ ID NO: 34), AAAguaggau (SEQ ID NO: 35), AAAguagggg (SEQ ID NO: 36), AAAguaggua (SEQ ID NO: 37), AAAguaguaa (SEQ ID NO: 38), AAAguauauu (SEQ ID NO: 39), AAAguauccu (SEQ ID NO: 40), AAAguaucuc (SEQ ID NO: 41), AAAguaugga (SEQ ID NO: 42), AAAguaugua (SEQ ID NO: 43), AAAguaugug (SEQ ID NO: 44), AAAguauguu (SEQ ID NO: 45), AAAguauugg (SEQ ID NO: 46), AAAguauuuu (SEQ ID NO: 47), AAAgucagau (SEQ ID NO: 48), AAAgucugag (SEQ ID NO: 49), AAAgugaaua (SEQ ID NO: 50), AAAgugagaa (SEQ ID NO: 51), AAAgugagac (SEQ ID NO: 52), AAAgugagag (SEQ ID NO: 53), AAAgugagau (SEQ ID NO: 54), AAAgugagca (SEQ ID NO: 55), AAAgugagcu (SEQ ID NO: 56), AAAgugaggg (SEQ ID NO: 57), AAAgugagua (SEQ ID NO: 58), AAAgugaguc (SEQ ID NO: 59), AAAgugagug (SEQ ID NO: 60), AAAgugaguu (SEQ ID NO: 61), AAAgugcguc (SEQ ID NO: 62), AAAgugcuga (SEQ ID NO: 63), AAAguggguc (SEQ ID NO: 64), AAAguggguu (SEQ ID NO: 65), AAAgugguaa (SEQ ID NO: 66), AAAguguaug (SEQ ID NO: 67), AAAgugugug (SEQ ID NO: 68), AAAguguguu (SEQ ID NO: 69), AAAguuaagu (SEQ ID NO: 70), AAAguuacuu (SEQ ID NO: 71), AAAguuagug (SEQ ID NO: 72), AAAguuaugu (SEQ ID NO: 73), AAAguugagu (SEQ ID NO: 74), AAAguuugua (SEQ ID NO: 75), AACguaaaac (SEQ ID NO: 76), AACguaaagc (SEQ ID NO: 77), AACguaaagg (SEQ ID NO: 78), AACguaagca (SEQ ID NO: 79), AACguaaggg (SEQ ID NO: 80), AACguaaguc (SEQ ID NO: 81), AACguaagug (SEQ ID NO: 82), AACguaaugg (SEQ ID NO: 83), AACguaguga (SEQ ID NO: 84), AACguaugua (SEQ ID NO: 85), AACguauguu (SEQ ID NO: 86), AACgugagca (SEQ ID NO: 87), AACgugagga (SEQ ID NO: 88), AACgugauuu (SEQ ID NO: 89), AACgugggau (SEQ ID NO: 90), AACgugggua (SEQ ID NO: 91), AACguguguu (SEQ ID NO: 92), AACguuggua (SEQ ID NO: 93), AAGgcaaauu (SEQ ID NO: 94), AAGgcaagag (SEQ ID NO: 95), AAGgcaagau (SEQ ID NO: 96), AAGgcaagcc (SEQ ID NO: 97), AAGgcaagga (SEQ ID NO: 98), AAGgcaaggg (SEQ ID NO: 99), AAGgcaagug (SEQ ID NO: 100), AAGgcaaguu (SEQ ID NO: 101), AAGgcacugc (SEQ ID NO: 102), AAGgcagaaa (SEQ ID NO: 103), AAGgcaggau (SEQ ID NO: 104), AAGgcaggca (SEQ ID NO: 105), AAGgcaggga (SEQ ID NO: 106), AAGgcagggg (SEQ ID NO: 107), AAGgcaggua (SEQ ID NO: 108), AAGgcaggug (SEQ ID NO: 109), AAGgcaucuc (SEQ ID NO: 110), AAGgcaugcu (SEQ ID NO: 111), AAGgcaugga (SEQ ID NO: 112), AAGgcauguu (SEQ ID NO: 113), AAGgcauuau (SEQ ID NO: 114), AAGgcgagcu (SEQ ID NO: 115), AAGgcgaguc (SEQ ID NO: 116), AAGgcgaguu (SEQ ID NO: 117), AAGgcuagcc (SEQ ID NO: 118), AAGguaaaaa (SEQ ID NO: 119), AAGguaaaac (SEQ ID NO: 120), AAGguaaaag (SEQ ID NO: 121), AAGguaaaau (SEQ ID NO: 122), AAGguaaaca (SEQ ID NO: 123), AAGguaaacc (SEQ ID NO: 124), AAGguaaacu (SEQ ID NO: 125), AAGguaaaga (SEQ ID NO: 126), AAGguaaagc (SEQ ID NO: 127), AAGguaaagg (SEQ ID NO: 128), AAGguaaagu (SEQ ID NO: 129), AAGguaaaua (SEQ ID NO: 130), AAGguaaauc (SEQ ID NO: 131), AAGguaaaug (SEQ ID NO: 132), AAGguaaauu (SEQ ID NO: 133), AAGguaacaa (SEQ ID NO: 134), AAGguaacau (SEQ ID NO: 135), AAGguaaccc (SEQ ID NO: 136), AAGguaacua (SEQ ID NO: 137), AAGguaacuc (SEQ ID NO: 138), AAGguaacug (SEQ ID NO: 139), AAGguaacuu (SEQ ID NO: 140), AAGguaagaa (SEQ ID NO: 141), AAGguaagac (SEQ ID NO: 142), AAGguaagag (SEQ ID NO: 143), AAGguaagau (SEQ ID NO: 144), AAGguaagca (SEQ ID NO: 145), AAGguaagcc (SEQ ID NO: 146), AAGguaagcg (SEQ ID NO: 147), AAGguaagcu (SEQ ID NO: 148), AAGguaagga (SEQ ID NO: 149), AAGguaaggc (SEQ ID NO: 150), AAGguaaggg (SEQ ID NO: 151), AAGguaaggu (SEQ ID NO: 152), AAGguaagua (SEQ ID NO: 153), AAGguaaguc (SEQ ID NO: 154), AAGguaagug (SEQ ID NO: 155), AAGguaaguu (SEQ ID NO: 156), AAGguaauaa (SEQ ID NO: 157), AAGguaauac (SEQ ID NO: 158), AAGguaauag (SEQ ID NO: 159), AAGguaauau (SEQ ID NO: 160), AAGguaauca (SEQ ID NO: 161), AAGguaaucc (SEQ ID NO: 162), AAGguaaucu (SEQ ID NO: 163), AAGguaauga (SEQ ID NO: 164), AAGguaaugc (SEQ ID NO: 165), AAGguaaugg (SEQ ID NO: 166), AAGguaaugu (SEQ ID NO: 167), AAGguaauua (SEQ ID NO: 168), AAGguaauuc (SEQ ID NO: 169), AAGguaauug (SEQ ID NO: 170), AAGguaauuu (SEQ ID NO: 171), AAGguacaaa (SEQ ID NO: 172), AAGguacaag (SEQ ID NO: 173), AAGguacaau (SEQ ID NO: 174), AAGguacacc (SEQ ID NO: 175), AAGguacacu (SEQ ID NO: 176), AAGguacagg (SEQ ID NO: 177), AAGguacagu (SEQ ID NO: 178), AAGguacaua (SEQ ID NO: 179), AAGguacaug (SEQ ID NO: 180), AAGguacauu (SEQ ID NO: 181), AAGguaccaa (SEQ ID NO: 182), AAGguaccag (SEQ ID NO: 183), AAGguaccca (SEQ ID NO: 184), AAGguacccu (SEQ ID NO: 185), AAGguaccuc (SEQ ID NO: 186), AAGguaccug (SEQ ID NO: 187), AAGguaccuu (SEQ ID NO: 188), AAGguacgaa (SEQ ID NO: 189), AAGguacggg (SEQ ID NO: 190), AAGguacggu (SEQ ID NO: 191), AAGguacguc (SEQ ID NO: 192), AAGguacguu (SEQ ID NO: 193), AAGguacuaa (SEQ ID NO: 194), AAGguacuau (SEQ ID NO: 195), AAGguacucu (SEQ ID NO: 196), AAGguacuga (SEQ ID NO: 197), AAGguacugc (SEQ ID NO: 198), AAGguacugu (SEQ ID NO: 199), AAGguacuuc (SEQ ID NO: 200), AAGguacuug (SEQ ID NO: 201), AAGguacuuu (SEQ ID NO: 202), AAGguagaaa (SEQ ID NO: 203), AAGguagaac (SEQ ID NO: 204), AAGguagaca (SEQ ID NO: 205), AAGguagacc (SEQ ID NO: 206), AAGguagacu (SEQ ID NO: 207), AAGguagagu (SEQ ID NO: 208), AAGguagaua (SEQ ID NO: 209), AAGguagcaa (SEQ ID NO: 210), AAGguagcag (SEQ ID NO: 211), AAGguagcca (SEQ ID NO: 212), AAGguagccu (SEQ ID NO: 213), AAGguagcua (SEQ ID NO: 214), AAGguagcug (SEQ ID NO: 215), AAGguagcuu (SEQ ID NO: 216), AAGguaggaa (SEQ ID NO: 217), AAGguaggag (SEQ ID NO: 218), AAGguaggau (SEQ ID NO: 219), AAGguaggca (SEQ ID NO: 220), AAGguaggcc (SEQ ID NO: 221), AAGguaggcu (SEQ ID NO: 222), AAGguaggga (SEQ ID NO: 223), AAGguagggc (SEQ ID NO: 224), AAGguagggg (SEQ ID NO: 225), AAGguagggu (SEQ ID NO: 226), AAGguaggua (SEQ ID NO: 227), AAGguagguc (SEQ ID NO: 228), AAGguaggug (SEQ ID NO: 229), AAGguagguu (SEQ ID NO: 230), AAGguaguaa (SEQ ID NO: 231), AAGguaguag (SEQ ID NO: 232), AAGguagucu (SEQ ID NO: 233), AAGguagugc (SEQ ID NO: 234), AAGguagugg (SEQ ID NO: 235), AAGguaguuc (SEQ ID NO: 236), AAGguaguuu (SEQ ID NO: 237), AAGguauaaa (SEQ ID NO: 238), AAGguauaau (SEQ ID NO: 239), AAGguauaca (SEQ ID NO: 240), AAGguauacu (SEQ ID NO: 241), AAGguauaua (SEQ ID NO: 242), AAGguauauc (SEQ ID NO: 243), AAGguauaug (SEQ ID NO: 244), AAGguauauu (SEQ ID NO: 245), AAGguaucac (SEQ ID NO: 246), AAGguaucag (SEQ ID NO: 247), AAGguauccc (SEQ ID NO: 248), AAGguauccu (SEQ ID NO: 249), AAGguaucuc (SEQ ID NO: 250), AAGguaucug (SEQ ID NO: 251), AAGguaucuu (SEQ ID NO: 252), AAGguaugaa (SEQ ID NO: 253), AAGguaugac (SEQ ID NO: 254), AAGguaugag (SEQ ID NO: 255), AAGguaugau (SEQ ID NO: 256), AAGguaugca (SEQ ID NO: 257), AAGguaugcc (SEQ ID NO: 258), AAGguaugcu (SEQ ID NO: 259), AAGguaugga (SEQ ID NO: 260), AAGguauggc (SEQ ID NO: 261), AAGguauggg (SEQ ID NO: 262), AAGguaugua (SEQ ID NO: 263), AAGguauguc (SEQ ID NO: 264), AAGguaugug (SEQ ID NO: 265), AAGguauguu (SEQ ID NO: 266), AAGguauuaa (SEQ ID NO: 267), AAGguauuac (SEQ ID NO: 268), AAGguauuag (SEQ ID NO: 269), AAGguauuau (SEQ ID NO: 270), AAGguauucc (SEQ ID NO: 271), AAGguauuga (SEQ ID NO: 272), AAGguauugu (SEQ ID NO: 273), AAGguauuua (SEQ ID NO: 274), AAGguauuuc (SEQ ID NO: 275), AAGguauuug (SEQ ID NO: 276), AAGguauuuu (SEQ ID NO: 277), AAGgucaaau (SEQ ID NO: 278), AAGgucaaga (SEQ ID NO: 279), AAGgucaagu (SEQ ID NO: 280), AAGgucacag (SEQ ID NO: 281), AAGgucagaa (SEQ ID NO: 282), AAGgucagac (SEQ ID NO: 283), AAGgucagag (SEQ ID NO: 284), AAGgucagca (SEQ ID NO: 285), AAGgucagcc (SEQ ID NO: 286), AAGgucagcg (SEQ ID NO: 287), AAGgucagcu (SEQ ID NO: 288), AAGgucagga (SEQ ID NO: 289), AAGgucaggc (SEQ ID NO: 290), AAGgucaggg (SEQ ID NO: 291), AAGgucaggu (SEQ ID NO: 292), AAGgucagua (SEQ ID NO: 293), AAGgucaguc (SEQ ID NO: 294), AAGgucagug (SEQ ID NO: 295), AAGgucaguu (SEQ ID NO: 296), AAGgucauag (SEQ ID NO: 297), AAGgucaucu (SEQ ID NO: 298), AAGguccaca (SEQ ID NO: 299), AAGguccaga (SEQ ID NO: 300), AAGguccaua (SEQ ID NO: 301), AAGgucccag (SEQ ID NO: 302), AAGgucccuc (SEQ ID NO: 303), AAGguccuuc (SEQ ID NO: 304), AAGgucgagg (SEQ ID NO: 305), AAGgucuaau (SEQ ID NO: 306), AAGgucuacc (SEQ ID NO: 307), AAGgucuaua (SEQ ID NO: 308), AAGgucuccu (SEQ ID NO: 309), AAGgucucug (SEQ ID NO: 310), AAGgucucuu (SEQ ID NO: 311), AAGgucugaa (SEQ ID NO: 312), AAGgucugag (SEQ ID NO: 313), AAGgucugga (SEQ ID NO: 314), AAGgucuggg (SEQ ID NO: 315), AAGgucugua (SEQ ID NO: 316), AAGgucuguu (SEQ ID NO: 317), AAGgucuucu (SEQ ID NO: 318), AAGgucuuuu (SEQ ID NO: 319), AAGgugaaac (SEQ ID NO: 320), AAGgugaaag (SEQ ID NO: 321), AAGgugaaau (SEQ ID NO: 322), AAGgugaacu (SEQ ID NO: 323), AAGgugaagc (SEQ ID NO: 324), AAGgugaagg (SEQ ID NO: 325), AAGgugaagu (SEQ ID NO: 326), AAGgugaaua (SEQ ID NO: 327), AAGgugaaug (SEQ ID NO: 328), AAGgugaauu (SEQ ID NO: 329), AAGgugacaa (SEQ ID NO: 330), AAGgugacag (SEQ ID NO: 331), AAGgugacau (SEQ ID NO: 332), AAGgugacug (SEQ ID NO: 333), AAGgugacuu (SEQ ID NO: 334), AAGgugagaa (SEQ ID NO: 335), AAGgugagac (SEQ ID NO: 336), AAGgugagag (SEQ ID NO: 337), AAGgugagau (SEQ ID NO: 338), AAGgugagca (SEQ ID NO: 339), AAGgugagcc (SEQ ID NO: 340), AAGgugagcg (SEQ ID NO: 341), AAGgugagcu (SEQ ID NO: 342), AAGgugagga (SEQ ID NO: 343), AAGgugaggc (SEQ ID NO: 344), AAGgugaggg (SEQ ID NO: 345), AAGgugaggu (SEQ ID NO: 346), AAGgugagua (SEQ ID NO: 347), AAGgugaguc (SEQ ID NO: 348), AAGgugagug (SEQ ID NO: 349), AAGgugaguu (SEQ ID NO: 350), AAGgugauaa (SEQ ID NO: 351), AAGgugauca (SEQ ID NO: 352), AAGgugaucc (SEQ ID NO: 353), AAGgugauga (SEQ ID NO: 354), AAGgugaugc (SEQ ID NO: 355), AAGgugaugu (SEQ ID NO: 356), AAGgugauua (SEQ ID NO: 357), AAGgugauug (SEQ ID NO: 358), AAGgugauuu (SEQ ID NO: 359), AAGgugcaca (SEQ ID NO: 360), AAGgugcauc (SEQ ID NO: 361), AAGgugcccu (SEQ ID NO: 362), AAGgugccug (SEQ ID NO: 363), AAGgugcgug (SEQ ID NO: 364), AAGgugcguu (SEQ ID NO: 365), AAGgugcucc (SEQ ID NO: 366), AAGgugcuga (SEQ ID NO: 367), AAGgugcugc (SEQ ID NO: 368), AAGgugcugg (SEQ ID NO: 369), AAGgugcuua (SEQ ID NO: 370), AAGgugcuuu (SEQ ID NO: 371), AAGguggaua (SEQ ID NO: 372), AAGguggcua (SEQ ID NO: 373), AAGguggcug (SEQ ID NO: 374), AAGguggcuu (SEQ ID NO: 375), AAGgugggaa (SEQ ID NO: 376), AAGgugggag (SEQ ID NO: 377), AAGgugggau (SEQ ID NO: 378), AAGgugggca (SEQ ID NO: 379), AAGgugggcc (SEQ ID NO: 380), AAGgugggcg (SEQ ID NO: 381), AAGgugggga (SEQ ID NO: 382), AAGguggggu (SEQ ID NO: 383), AAGgugggua (SEQ ID NO: 384), AAGgugggug (SEQ ID NO: 385), AAGguggguu (SEQ ID NO: 386), AAGgugguaa (SEQ ID NO: 387), AAGgugguac (SEQ ID NO: 388), AAGgugguau (SEQ ID NO: 389), AAGguggugg (SEQ ID NO: 390), AAGgugguua (SEQ ID NO: 391), AAGgugguuc (SEQ ID NO: 392), AAGgugguuu (SEQ ID NO: 393), AAGguguaag (SEQ ID NO: 394), AAGgugucaa (SEQ ID NO: 395), AAGgugucag (SEQ ID NO: 396), AAGgugucug (SEQ ID NO: 397), AAGgugugaa (SEQ ID NO: 398), AAGgugugag (SEQ ID NO: 399), AAGgugugca (SEQ ID NO: 400), AAGgugugga (SEQ ID NO: 401), AAGguguggu (SEQ ID NO: 402), AAGgugugua (SEQ ID NO: 403), AAGguguguc (SEQ ID NO: 404), AAGgugugug (SEQ ID NO: 405), AAGguguguu (SEQ ID NO: 406), AAGguguucu (SEQ ID NO: 407), AAGguguugc (SEQ ID NO: 408), AAGguguugg (SEQ ID NO: 409), AAGguguuug (SEQ ID NO: 410), AAGguuaaaa (SEQ ID NO: 411), AAGguuaaca (SEQ ID NO: 412), AAGguuaagc (SEQ ID NO: 413), AAGguuaauu (SEQ ID NO: 414), AAGguuacau (SEQ ID NO: 415), AAGguuagaa (SEQ ID NO: 416), AAGguuagau (SEQ ID NO: 417), AAGguuagca (SEQ ID NO: 418), AAGguuagcc (SEQ ID NO: 419), AAGguuagga (SEQ ID NO: 420), AAGguuaggc (SEQ ID NO: 421), AAGguuagua (SEQ ID NO: 422), AAGguuaguc (SEQ ID NO: 423), AAGguuagug (SEQ ID NO: 424), AAGguuaguu (SEQ ID NO: 425), AAGguuauag (SEQ ID NO: 426), AAGguuauga (SEQ ID NO: 427), AAGguucaaa (SEQ ID NO: 428), AAGguucaag (SEQ ID NO: 429), AAGguuccuu (SEQ ID NO: 430), AAGguucggc (SEQ ID NO: 431), AAGguucguu (SEQ ID NO: 432), AAGguucuaa (SEQ ID NO: 433), AAGguucuga (SEQ ID NO: 434), AAGguucuua (SEQ ID NO: 435), AAGguugaau (SEQ ID NO: 436), AAGguugacu (SEQ ID NO: 437), AAGguugagg (SEQ ID NO: 438), AAGguugagu (SEQ ID NO: 439), AAGguugaua (SEQ ID NO: 440), AAGguugcac (SEQ ID NO: 441), AAGguugcug (SEQ ID NO: 442), AAGguuggaa (SEQ ID NO: 443), AAGguuggca (SEQ ID NO: 444), AAGguuggga (SEQ ID NO: 445), AAGguugggg (SEQ ID NO: 446), AAGguuggua (SEQ ID NO: 447), AAGguugguc (SEQ ID NO: 448), AAGguuggug (SEQ ID NO: 449), AAGguugguu (SEQ ID NO: 450), AAGguuguaa (SEQ ID NO: 451), AAGguugucc (SEQ ID NO: 452), AAGguugugc (SEQ ID NO: 453), AAGguuguua (SEQ ID NO: 454), AAGguuuacc (SEQ ID NO: 455), AAGguuuaua (SEQ ID NO: 456), AAGguuuauu (SEQ ID NO: 457), AAGguuuccu (SEQ ID NO: 458), AAGguuucgu (SEQ ID NO: 459), AAGguuugag (SEQ ID NO: 460), AAGguuugca (SEQ ID NO: 461), AAGguuugcc (SEQ ID NO: 462), AAGguuugcu (SEQ ID NO: 463), AAGguuugga (SEQ ID NO: 464), AAGguuuggu (SEQ ID NO: 465), AAGguuugua (SEQ ID NO: 466), AAGguuuguc (SEQ ID NO: 467), AAGguuugug (SEQ ID NO: 468), AAGguuuuaa (SEQ ID NO: 469), AAGguuuuca (SEQ ID NO: 470), AAGguuuucg (SEQ ID NO: 471), AAGguuuugc (SEQ ID NO: 472), AAGguuuugu (SEQ ID NO: 473), AAGguuuuuu (SEQ ID NO: 474), AAUgcaagua (SEQ ID NO: 475), AAUgcaaguc (SEQ ID NO: 476), AAUguaaaca (SEQ ID NO: 477), AAUguaaaua (SEQ ID NO: 478), AAUguaaauc (SEQ ID NO: 479), AAUguaaaug (SEQ ID NO: 480), AAUguaaauu (SEQ ID NO: 481), AAUguaacua (SEQ ID NO: 482), AAUguaagaa (SEQ ID NO: 483), AAUguaagag (SEQ ID NO: 484), AAUguaagau (SEQ ID NO: 485), AAUguaagcc (SEQ ID NO: 486), AAUguaagcu (SEQ ID NO: 487), AAUguaagga (SEQ ID NO: 488), AAUguaagua (SEQ ID NO: 489), AAUguaaguc (SEQ ID NO: 490), AAUguaagug (SEQ ID NO: 491), AAUguaaguu (SEQ ID NO: 492), AAUguaauca (SEQ ID NO: 493), AAUguaauga (SEQ ID NO: 494), AAUguaaugu (SEQ ID NO: 495), AAUguacauc (SEQ ID NO: 496), AAUguacaug (SEQ ID NO: 497), AAUguacgau (SEQ ID NO: 498), AAUguacgua (SEQ ID NO: 499), AAUguacguc (SEQ ID NO: 500), AAUguacgug (SEQ ID NO: 501), AAUguacucu (SEQ ID NO: 502), AAUguaggca (SEQ ID NO: 503), AAUguagguu (SEQ ID NO: 504), AAUguaucua (SEQ ID NO: 505), AAUguaugaa (SEQ ID NO: 506), AAUguaugua (SEQ ID NO: 507), AAUguaugug (SEQ ID NO: 508), AAUguauguu (SEQ ID NO: 509), AAUgucagag (SEQ ID NO: 510), AAUgucagau (SEQ ID NO: 511), AAUgucagcu (SEQ ID NO: 512), AAUgucagua (SEQ ID NO: 513), AAUgucaguc (SEQ ID NO: 514), AAUgucagug (SEQ ID NO: 515), AAUgucaguu (SEQ ID NO: 516), AAUgucggua (SEQ ID NO: 517), AAUgucuguu (SEQ ID NO: 518), AAUgugagaa (SEQ ID NO: 519), AAUgugagca (SEQ ID NO: 520), AAUgugagcc (SEQ ID NO: 521), AAUgugagga (SEQ ID NO: 522), AAUgugagua (SEQ ID NO: 523), AAUgugaguc (SEQ ID NO: 524), AAUgugagug (SEQ ID NO: 525), AAUgugaguu (SEQ ID NO: 526), AAUgugauau (SEQ ID NO: 527), AAUgugcaua (SEQ ID NO: 528), AAUgugcgua (SEQ ID NO: 529), AAUgugcguc (SEQ ID NO: 530), AAUgugggac (SEQ ID NO: 531), AAUguggguc (SEQ ID NO: 532), AAUgugggug (SEQ ID NO: 533), AAUgugguuu (SEQ ID NO: 534), AAUgugugua (SEQ ID NO: 535), AAUguuaagu (SEQ ID NO: 536), AAUguuagaa (SEQ ID NO: 537), AAUguuagau (SEQ ID NO: 538), AAUguuagua (SEQ ID NO: 539), AAUguuggug (SEQ ID NO: 540), ACAgcaagua (SEQ ID NO: 541), ACAguaaaua (SEQ ID NO: 542), ACAguaaaug (SEQ ID NO: 543), ACAguaagaa (SEQ ID NO: 544), ACAguaagca (SEQ ID NO: 545), ACAguaagua (SEQ ID NO: 546), ACAguaaguc (SEQ ID NO: 547), ACAguaagug (SEQ ID NO: 548), ACAguaaguu (SEQ ID NO: 549), ACAguacgua (SEQ ID NO: 550), ACAguaggug (SEQ ID NO: 551), ACAguauaac (SEQ ID NO: 552), ACAguaugua (SEQ ID NO: 553), ACAgucaguu (SEQ ID NO: 554), ACAgugagaa (SEQ ID NO: 555), ACAgugagcc (SEQ ID NO: 556), ACAgugagcu (SEQ ID NO: 557), ACAgugagga (SEQ ID NO: 558), ACAgugaggu (SEQ ID NO: 559), ACAgugagua (SEQ ID NO: 560), ACAgugaguc (SEQ ID NO: 561), ACAgugagug (SEQ ID NO: 562), ACAgugaguu (SEQ ID NO: 563), ACAgugggua (SEQ ID NO: 564), ACAguggguu (SEQ ID NO: 565), ACAguguaaa (SEQ ID NO: 566), ACAguuaagc (SEQ ID NO: 567), ACAguuaagu (SEQ ID NO: 568), ACAguuaugu (SEQ ID NO: 569), ACAguugagu (SEQ ID NO: 570), ACAguuguga (SEQ ID NO: 571), ACCguaagua (SEQ ID NO: 572), ACCgugagaa (SEQ ID NO: 573), ACCgugagca (SEQ ID NO: 574), ACCgugaguu (SEQ ID NO: 575), ACCgugggug (SEQ ID NO: 576), ACGguaaaac (SEQ ID NO: 577), ACGguaacua (SEQ ID NO: 578), ACGguaagua (SEQ ID NO: 579), ACGguaagug (SEQ ID NO: 580), ACGguaaguu (SEQ ID NO: 581), ACGguaauua (SEQ ID NO: 582), ACGguaauuu (SEQ ID NO: 583), ACGguacaau (SEQ ID NO: 584), ACGguacagu (SEQ ID NO: 585), ACGguaccag (SEQ ID NO: 586), ACGguacggu (SEQ ID NO: 587), ACGguacgua (SEQ ID NO: 588), ACGguaggaa (SEQ ID NO: 589), ACGguaggag (SEQ ID NO: 590), ACGguaggug (SEQ ID NO: 591), ACGguaguaa (SEQ ID NO: 592), ACGguauaau (SEQ ID NO: 593), ACGguaugac (SEQ ID NO: 594), ACGguaugcg (SEQ ID NO: 595), ACGguaugua (SEQ ID NO: 596), ACGguauguc (SEQ ID NO: 597), ACGgugaaac (SEQ ID NO: 598), ACGgugaagu (SEQ ID NO: 599), ACGgugaauc (SEQ ID NO: 600), ACGgugacag (SEQ ID NO: 601), ACGgugacca (SEQ ID NO: 602), ACGgugagaa (SEQ ID NO: 603), ACGgugagau (SEQ ID NO: 604), ACGgugagcc (SEQ ID NO: 605), ACGgugagua (SEQ ID NO: 606), ACGgugagug (SEQ ID NO: 607), ACGgugaguu (SEQ ID NO: 608), ACGgugcgug (SEQ ID NO: 609), ACGguggcac (SEQ ID NO: 610), ACGguggggc (SEQ ID NO: 611), ACGgugggug (SEQ ID NO: 612), ACGguguagu (SEQ ID NO: 613), ACGgugucac (SEQ ID NO: 614), ACGgugugua (SEQ ID NO: 615), ACGguguguu (SEQ ID NO: 616), ACGguuagug (SEQ ID NO: 617), ACGguuaguu (SEQ ID NO: 618), ACGguucaau (SEQ ID NO: 619), ACUguaaaua (SEQ ID NO: 620), ACUguaagaa (SEQ ID NO: 621), ACUguaagac (SEQ ID NO: 622), ACUguaagca (SEQ ID NO: 623), ACUguaagcu (SEQ ID NO: 624), ACUguaagua (SEQ ID NO: 625), ACUguaaguc (SEQ ID NO: 626), ACUguaaguu (SEQ ID NO: 627), ACUguacguu (SEQ ID NO: 628), ACUguacugc (SEQ ID NO: 629), ACUguaggcu (SEQ ID NO: 630), ACUguaggua (SEQ ID NO: 631), ACUguauauu (SEQ ID NO: 632), ACUguaugaa (SEQ ID NO: 633), ACUguaugcu (SEQ ID NO: 634), ACUguaugug (SEQ ID NO: 635), ACUguauucc (SEQ ID NO: 636), ACUgucagcu (SEQ ID NO: 637), ACUgucagug (SEQ ID NO: 638), ACUgugaacg (SEQ ID NO: 639), ACUgugagca (SEQ ID NO: 640), ACUgugagcg (SEQ ID NO: 641), ACUgugagcu (SEQ ID NO: 642), ACUgugagua (SEQ ID NO: 643), ACUgugaguc (SEQ ID NO: 644), ACUgugagug (SEQ ID NO: 645), ACUgugaguu (SEQ ID NO: 646), ACUgugggua (SEQ ID NO: 647), ACUgugugug (SEQ ID NO: 648), ACUguuaagu (SEQ ID NO: 649), AGAgcaagua (SEQ ID NO: 650), AGAguaaaac (SEQ ID NO: 651), AGAguaaacg (SEQ ID NO: 652), AGAguaaaga (SEQ ID NO: 653), AGAguaaagu (SEQ ID NO: 654), AGAguaaauc (SEQ ID NO: 655), AGAguaaaug (SEQ ID NO: 656), AGAguaacau (SEQ ID NO: 657), AGAguaacua (SEQ ID NO: 658), AGAguaagaa (SEQ ID NO: 659), AGAguaagac (SEQ ID NO: 660), AGAguaagag (SEQ ID NO: 661), AGAguaagau (SEQ ID NO: 662), AGAguaagca (SEQ ID NO: 663), AGAguaagcu (SEQ ID NO: 664), AGAguaagga (SEQ ID NO: 665), AGAguaaggc (SEQ ID NO: 666), AGAguaaggg (SEQ ID NO: 667), AGAguaaggu (SEQ ID NO: 668), AGAguaaguc (SEQ ID NO: 669), AGAguaagug (SEQ ID NO: 670), AGAguaaguu (SEQ ID NO: 671), AGAguaauaa (SEQ ID NO: 672), AGAguaaugu (SEQ ID NO: 673), AGAguaauuc (SEQ ID NO: 674), AGAguaauuu (SEQ ID NO: 675), AGAguacacc (SEQ ID NO: 676), AGAguaccug (SEQ ID NO: 677), AGAguacgug (SEQ ID NO: 678), AGAguacucu (SEQ ID NO: 679), AGAguacuga (SEQ ID NO: 680), AGAguacuuu (SEQ ID NO: 681), AGAguagcug (SEQ ID NO: 682), AGAguaggaa (SEQ ID NO: 683), AGAguaggga (SEQ ID NO: 684), AGAguagggu (SEQ ID NO: 685), AGAguagguc (SEQ ID NO: 686), AGAguaggug (SEQ ID NO: 687), AGAguagguu (SEQ ID NO: 688), AGAguauaua (SEQ ID NO: 689), AGAguauauu (SEQ ID NO: 690), AGAguaugaa (SEQ ID NO: 691), AGAguaugac (SEQ ID NO: 692), AGAguaugau (SEQ ID NO: 693), AGAguauguc (SEQ ID NO: 694), AGAguaugug (SEQ ID NO: 695), AGAguauguu (SEQ ID NO: 696), AGAguauuaa (SEQ ID NO: 697), AGAguauuau (SEQ ID NO: 698), AGAgucagug (SEQ ID NO: 699), AGAgugagac (SEQ ID NO: 700), AGAgugagag (SEQ ID NO: 701), AGAgugagau (SEQ ID NO: 702), AGAgugagca (SEQ ID NO: 703), AGAgugagua (SEQ ID NO: 704), AGAgugaguc (SEQ ID NO: 705), AGAgugagug (SEQ ID NO: 706), AGAgugaguu (SEQ ID NO: 707), AGAgugcguc (SEQ ID NO: 708), AGAgugggga (SEQ ID NO: 709), AGAgugggug (SEQ ID NO: 710), AGAgugugug (SEQ ID NO: 711), AGAguguuuc (SEQ ID NO: 712), AGAguuagua (SEQ ID NO: 713), AGAguugaga (SEQ ID NO: 714), AGAguugagu (SEQ ID NO: 715), AGAguugguu (SEQ ID NO: 716), AGAguuugau (SEQ ID NO: 717), AGCguaagcu (SEQ ID NO: 718), AGCguaagug (SEQ ID NO: 719), AGCgugagcc (SEQ ID NO: 720), AGCgugagug (SEQ ID NO: 721), AGCguuguuc (SEQ ID NO: 722), AGGgcagagu (SEQ ID NO: 723), AGGgcagccu (SEQ ID NO: 724), AGGgcuagua (SEQ ID NO: 725), AGGguaaaga (SEQ ID NO: 726), AGGguaaaua (SEQ ID NO: 727), AGGguaaauc (SEQ ID NO: 728), AGGguaaauu (SEQ ID NO: 729), AGGguaacca (SEQ ID NO: 730), AGGguaacug (SEQ ID NO: 731), AGGguaacuu (SEQ ID NO: 732), AGGguaagaa (SEQ ID NO: 733), AGGguaagag (SEQ ID NO: 734), AGGguaagau (SEQ ID NO: 735), AGGguaagca (SEQ ID NO: 736), AGGguaagga (SEQ ID NO: 737), AGGguaaggc (SEQ ID NO: 738), AGGguaaggg (SEQ ID NO: 739), AGGguaagua (SEQ ID NO: 740), AGGguaaguc (SEQ ID NO: 741), AGGguaagug (SEQ ID NO: 742), AGGguaaguu (SEQ ID NO: 743), AGGguaauac (SEQ ID NO: 744), AGGguaauga (SEQ ID NO: 745), AGGguaauua (SEQ ID NO: 746), AGGguaauuu (SEQ ID NO: 747), AGGguacacc (SEQ ID NO: 748), AGGguacagu (SEQ ID NO: 749), AGGguacggu (SEQ ID NO: 750), AGGguaggac (SEQ ID NO: 751), AGGguaggag (SEQ ID NO: 752), AGGguaggca (SEQ ID NO: 753), AGGguaggcc (SEQ ID NO: 754), AGGguaggga (SEQ ID NO: 755), AGGguagggu (SEQ ID NO: 756), AGGguagguc (SEQ ID NO: 757), AGGguaggug (SEQ ID NO: 758), AGGguagguu (SEQ ID NO: 759), AGGguauaua (SEQ ID NO: 760), AGGguaugac (SEQ ID NO: 761), AGGguaugag (SEQ ID NO: 762), AGGguaugau (SEQ ID NO: 763), AGGguaugca (SEQ ID NO: 764), AGGguaugcu (SEQ ID NO: 765), AGGguauggg (SEQ ID NO: 766), AGGguauggu (SEQ ID NO: 767), AGGguaugua (SEQ ID NO: 768), AGGguauguc (SEQ ID NO: 769), AGGguaugug (SEQ ID NO: 770), AGGguauuac (SEQ ID NO: 771), AGGguauucu (SEQ ID NO: 772), AGGguauuuc (SEQ ID NO: 773), AGGgucagag (SEQ ID NO: 774), AGGgucagca (SEQ ID NO: 775), AGGgucagga (SEQ ID NO: 776), AGGgucaggg (SEQ ID NO: 777), AGGgucagug (SEQ ID NO: 778), AGGgucaguu (SEQ ID NO: 779), AGGguccccu (SEQ ID NO: 780), AGGgucggga (SEQ ID NO: 781), AGGgucugca (SEQ ID NO: 782), AGGgucuguu (SEQ ID NO: 783), AGGgugaaga (SEQ ID NO: 784), AGGgugacua (SEQ ID NO: 785), AGGgugagaa (SEQ ID NO: 786), AGGgugagac (SEQ ID NO: 787), AGGgugagag (SEQ ID NO: 788), AGGgugagca (SEQ ID NO: 789), AGGgugagcc (SEQ ID NO: 790), AGGgugagcu (SEQ ID NO: 791), AGGgugagga (SEQ ID NO: 792), AGGgugaggg (SEQ ID NO: 793), AGGgugaggu (SEQ ID NO: 794), AGGgugagua (SEQ ID NO: 795), AGGgugaguc (SEQ ID NO: 796), AGGgugagug (SEQ ID NO: 797), AGGgugaguu (SEQ ID NO: 798), AGGgugggga (SEQ ID NO: 799), AGGguggggu (SEQ ID NO: 800), AGGgugggua (SEQ ID NO: 801), AGGgugggug (SEQ ID NO: 802), AGGgugugua (SEQ ID NO: 803), AGGgugugug (SEQ ID NO: 804), AGGguuaaug (SEQ ID NO: 805), AGGguuagaa (SEQ ID NO: 806), AGGguuaguu (SEQ ID NO: 807), AGGguuggug (SEQ ID NO: 808), AGGguuugug (SEQ ID NO: 809), AGGguuuguu (SEQ ID NO: 810), AGUguaaaag (SEQ ID NO: 811), AGUguaaaua (SEQ ID NO: 812), AGUguaaauu (SEQ ID NO: 813), AGUguaagaa (SEQ ID NO: 814), AGUguaagag (SEQ ID NO: 815), AGUguaagau (SEQ ID NO: 816), AGUguaagca (SEQ ID NO: 817), AGUguaagcc (SEQ ID NO: 818), AGUguaagua (SEQ ID NO: 819), AGUguaagug (SEQ ID NO: 820), AGUguaaguu (SEQ ID NO: 821), AGUguaauug (SEQ ID NO: 822), AGUguaggac (SEQ ID NO: 823), AGUguagguc (SEQ ID NO: 824), AGUguaugag (SEQ ID NO: 825), AGUguaugua (SEQ ID NO: 826), AGUguauguu (SEQ ID NO: 827), AGUguauugu (SEQ ID NO: 828), AGUguauuua (SEQ ID NO: 829), AGUgucaguc (SEQ ID NO: 830), AGUgugagag (SEQ ID NO: 831), AGUgugagca (SEQ ID NO: 832), AGUgugagcc (SEQ ID NO: 833), AGUgugagcu (SEQ ID NO: 834), AGUgugagua (SEQ ID NO: 835), AGUgugaguc (SEQ ID NO: 836), AGUgugagug (SEQ ID NO: 837), AGUgugaguu (SEQ ID NO: 838), AGUgugggua (SEQ ID NO: 839), AGUgugggug (SEQ ID NO: 840), AGUgugugua (SEQ ID NO: 841), AGUguuccua (SEQ ID NO: 842), AGUguugggg (SEQ ID NO: 843), AGUguuucag (SEQ ID NO: 844), AUAguaaaua (SEQ ID NO: 845), AUAguaagac (SEQ ID NO: 846), AUAguaagau (SEQ ID NO: 847), AUAguaagca (SEQ ID NO: 848), AUAguaagua (SEQ ID NO: 849), AUAguaagug (SEQ ID NO: 850), AUAguaaguu (SEQ ID NO: 851), AUAguaggua (SEQ ID NO: 852), AUAguauguu (SEQ ID NO: 853), AUAgucucac (SEQ ID NO: 854), AUAgugagac (SEQ ID NO: 855), AUAgugagag (SEQ ID NO: 856), AUAgugagau (SEQ ID NO: 857), AUAgugagcc (SEQ ID NO: 858), AUAgugaggc (SEQ ID NO: 859), AUAgugagua (SEQ ID NO: 860), AUAgugaguc (SEQ ID NO: 861), AUAgugagug (SEQ ID NO: 862), AUAgugcguc (SEQ ID NO: 863), AUAgugugua (SEQ ID NO: 864), AUAguucagu (SEQ ID NO: 865), AUCguaagcc (SEQ ID NO: 866), AUCguaaguu (SEQ ID NO: 867), AUCguauucc (SEQ ID NO: 868), AUCgugagua (SEQ ID NO: 869), AUGgcaagcg (SEQ ID NO: 870), AUGgcaagga (SEQ ID NO: 871), AUGgcaaguu (SEQ ID NO: 872), AUGgcaggua (SEQ ID NO: 873), AUGgcaugug (SEQ ID NO: 874), AUGgcgccau (SEQ ID NO: 875), AUGgcuugug (SEQ ID NO: 876), AUGguaaaac (SEQ ID NO: 877), AUGguaaaau (SEQ ID NO: 878), AUGguaaacc (SEQ ID NO: 879), AUGguaaaga (SEQ ID NO: 880), AUGguaaaua (SEQ ID NO: 881), AUGguaaaug (SEQ ID NO: 882), AUGguaaauu (SEQ ID NO: 883), AUGguaacag (SEQ ID NO: 884), AUGguaacau (SEQ ID NO: 885), AUGguaacua (SEQ ID NO: 886), AUGguaacuc (SEQ ID NO: 887), AUGguaacuu (SEQ ID NO: 888), AUGguaagaa (SEQ ID NO: 889), AUGguaagac (SEQ ID NO: 890), AUGguaagag (SEQ ID NO: 891), AUGguaagau (SEQ ID NO: 892), AUGguaagca (SEQ ID NO: 893), AUGguaagcc (SEQ ID NO: 894), AUGguaagcu (SEQ ID NO: 895), AUGguaagga (SEQ ID NO: 896), AUGguaaggg (SEQ ID NO: 897), AUGguaagua (SEQ ID NO: 898), AUGguaaguc (SEQ ID NO: 899), AUGguaagug (SEQ ID NO: 900), AUGguaaguu (SEQ ID NO: 901), AUGguaauaa (SEQ ID NO: 902), AUGguaauau (SEQ ID NO: 903), AUGguaauga (SEQ ID NO: 904), AUGguaaugg (SEQ ID NO: 905), AUGguaauug (SEQ ID NO: 906), AUGguaauuu (SEQ ID NO: 907), AUGguacagc (SEQ ID NO: 908), AUGguacauc (SEQ ID NO: 909), AUGguaccag (SEQ ID NO: 910), AUGguaccug (SEQ ID NO: 911), AUGguacgag (SEQ ID NO: 912), AUGguacggu (SEQ ID NO: 913), AUGguagauc (SEQ ID NO: 914), AUGguagcag (SEQ ID NO: 915), AUGguagcug (SEQ ID NO: 916), AUGguaggaa (SEQ ID NO: 917), AUGguaggau (SEQ ID NO: 918), AUGguaggca (SEQ ID NO: 919), AUGguaggcu (SEQ ID NO: 920), AUGguagggg (SEQ ID NO: 921), AUGguagggu (SEQ ID NO: 922), AUGguaggua (SEQ ID NO: 923), AUGguaggug (SEQ ID NO: 924), AUGguaguuu (SEQ ID NO: 925), AUGguauagu (SEQ ID NO: 926), AUGguauaua (SEQ ID NO: 927), AUGguaucag (SEQ ID NO: 928), AUGguaucuu (SEQ ID NO: 929), AUGguaugau (SEQ ID NO: 930), AUGguaugca (SEQ ID NO: 931), AUGguaugcc (SEQ ID NO: 932), AUGguaugcg (SEQ ID NO: 933), AUGguaugcu (SEQ ID NO: 934), AUGguaugga (SEQ ID NO: 935), AUGguauggc (SEQ ID NO: 936), AUGguaugug (SEQ ID NO: 937), AUGguauguu (SEQ ID NO: 938), AUGguauuau (SEQ ID NO: 939), AUGguauuga (SEQ ID NO: 940), AUGguauuug (SEQ ID NO: 941), AUGgucaggg (SEQ ID NO: 942), AUGgucaguc (SEQ ID NO: 943), AUGgucagug (SEQ ID NO: 944), AUGgucauuu (SEQ ID NO: 945), AUGgugaaaa (SEQ ID NO: 946), AUGgugaaac (SEQ ID NO: 947), AUGgugaaau (SEQ ID NO: 948), AUGgugaacu (SEQ ID NO: 949), AUGgugaaga (SEQ ID NO: 950), AUGgugacgu (SEQ ID NO: 951), AUGgugagaa (SEQ ID NO: 952), AUGgugagac (SEQ ID NO: 953), AUGgugagag (SEQ ID NO: 954), AUGgugagca (SEQ ID NO: 955), AUGgugagcc (SEQ ID NO: 956), AUGgugagcg (SEQ ID NO: 957), AUGgugagcu (SEQ ID NO: 958), AUGgugaggc (SEQ ID NO: 959), AUGgugaggg (SEQ ID NO: 960), AUGgugagua (SEQ ID NO: 961), AUGgugaguc (SEQ ID NO: 962), AUGgugagug (SEQ ID NO: 963), AUGgugaguu (SEQ ID NO: 964), AUGgugauuu (SEQ ID NO: 965), AUGgugcgau (SEQ ID NO: 966), AUGgugcgug (SEQ ID NO: 967), AUGgugggua (SEQ ID NO: 968), AUGgugggug (SEQ ID NO: 969), AUGguggguu (SEQ ID NO: 970), AUGgugguua (SEQ ID NO: 971), AUGguguaag (SEQ ID NO: 972), AUGgugugaa (SEQ ID NO: 973), AUGgugugua (SEQ ID NO: 974), AUGgugugug (SEQ ID NO: 975), AUGguuacuc (SEQ ID NO: 976), AUGguuagca (SEQ ID NO: 977), AUGguuaguc (SEQ ID NO: 978), AUGguuagug (SEQ ID NO: 979), AUGguuaguu (SEQ ID NO: 980), AUGguucagu (SEQ ID NO: 981), AUGguucguc (SEQ ID NO: 982), AUGguuggua (SEQ ID NO: 983), AUGguugguc (SEQ ID NO: 984), AUGguugguu (SEQ ID NO: 985), AUGguuguuu (SEQ ID NO: 986), AUGguuugca (SEQ ID NO: 987), AUGguuugua (SEQ ID NO: 988), AUUgcaagua (SEQ ID NO: 989), AUUguaaaua (SEQ ID NO: 990), AUUguaagau (SEQ ID NO: 991), AUUguaagca (SEQ ID NO: 992), AUUguaagga (SEQ ID NO: 993), AUUguaaggc (SEQ ID NO: 994), AUUguaagua (SEQ ID NO: 995), AUUguaaguc (SEQ ID NO: 996), AUUguaaguu (SEQ ID NO: 997), AUUguaauua (SEQ ID NO: 998), AUUguaauuu (SEQ ID NO: 999), AUUguacaaa (SEQ ID NO: 1000), AUUguaccuc (SEQ ID NO: 1001), AUUguacgug (SEQ ID NO: 1002), AUUguacuug (SEQ ID NO: 1003), AUUguaggua (SEQ ID NO: 1004), AUUguaugag (SEQ ID NO: 1005), AUUguaugua (SEQ ID NO: 1006), AUUgucuguu (SEQ ID NO: 1007), AUUgugagcu (SEQ ID NO: 1008), AUUgugagua (SEQ ID NO: 1009), AUUgugaguc (SEQ ID NO: 1010), AUUgugaguu (SEQ ID NO: 1011), AUUgugcgug (SEQ ID NO: 1012), AUUgugggug (SEQ ID NO: 1013), AUUguuagug (SEQ ID NO: 1014), CAAguaaaaa (SEQ ID NO: 1015), CAAguaaaua (SEQ ID NO: 1016), CAAguaaauc (SEQ ID NO: 1017), CAAguaaaug (SEQ ID NO: 1018), CAAguaaccc (SEQ ID NO: 1019), CAAguaacua (SEQ ID NO: 1020), CAAguaacug (SEQ ID NO: 1021), CAAguaagaa (SEQ ID NO: 1022), CAAguaagac (SEQ ID NO: 1023), CAAguaagau (SEQ ID NO: 1024), CAAguaaggu (SEQ ID NO: 1025), CAAguaagua (SEQ ID NO: 1026), CAAguaaguc (SEQ ID NO: 1027), CAAguaagug (SEQ ID NO: 1028), CAAguaaguu (SEQ ID NO: 1029), CAAguaaucc (SEQ ID NO: 1030), CAAguaaucu (SEQ ID NO: 1031), CAAguaauua (SEQ ID NO: 1032), CAAguaauuc (SEQ ID NO: 1033), CAAguaauug (SEQ ID NO: 1034), CAAguaauuu (SEQ ID NO: 1035), CAAguacaca (SEQ ID NO: 1036), CAAguacguu (SEQ ID NO: 1037), CAAguacuuu (SEQ ID NO: 1038), CAAguagcug (SEQ ID NO: 1039), CAAguaggau (SEQ ID NO: 1040), CAAguaggua (SEQ ID NO: 1041), CAAguagguc (SEQ ID NO: 1042), CAAguaggug (SEQ ID NO: 1043), CAAguagguu (SEQ ID NO: 1044), CAAguaguuu (SEQ ID NO: 1045), CAAguauaac (SEQ ID NO: 1046), CAAguauaug (SEQ ID NO: 1047), CAAguaucuu (SEQ ID NO: 1048), CAAguaugag (SEQ ID NO: 1049), CAAguaugua (SEQ ID NO: 1050), CAAguauguc (SEQ ID NO: 1051), CAAguaugug (SEQ ID NO: 1052), CAAguauguu (SEQ ID NO: 1053), CAAguauuga (SEQ ID NO: 1054), CAAguauuuc (SEQ ID NO: 1055), CAAgucagac (SEQ ID NO: 1056), CAAgucagua (SEQ ID NO: 1057), CAAgucuaua (SEQ ID NO: 1058), CAAgucugau (SEQ ID NO: 1059), CAAgugacuu (SEQ ID NO: 1060), CAAgugagaa (SEQ ID NO: 1061), CAAgugagac (SEQ ID NO: 1062), CAAgugagca (SEQ ID NO: 1063), CAAgugaggc (SEQ ID NO: 1064), CAAgugaggg (SEQ ID NO: 1065), CAAgugagua (SEQ ID NO: 1066), CAAgugaguc (SEQ ID NO: 1067), CAAgugagug (SEQ ID NO: 1068), CAAgugaucc (SEQ ID NO: 1069), CAAgugaucu (SEQ ID NO: 1070), CAAgugauuc (SEQ ID NO: 1071), CAAgugauug (SEQ ID NO: 1072), CAAgugauuu (SEQ ID NO: 1073), CAAgugccuu (SEQ ID NO: 1074), CAAgugggua (SEQ ID NO: 1075), CAAguggguc (SEQ ID NO: 1076), CAAgugggug (SEQ ID NO: 1077), CAAgugugag (SEQ ID NO: 1078), CAAguuaaaa (SEQ ID NO: 1079), CAAguuaagu (SEQ ID NO: 1080), CAAguuaauc (SEQ ID NO: 1081), CAAguuagaa (SEQ ID NO: 1082), CAAguuaguu (SEQ ID NO: 1083), CAAguucaag (SEQ ID NO: 1084), CAAguuccgu (SEQ ID NO: 1085), CAAguuggua (SEQ ID NO: 1086), CAAguuuagu (SEQ ID NO: 1087), CAAguuucca (SEQ ID NO: 1088), CAAguuuguu (SEQ ID NO: 1089), CACguaagag (SEQ ID NO: 1090), CACguaagca (SEQ ID NO: 1091), CACguaauug (SEQ ID NO: 1092), CACguaggac (SEQ ID NO: 1093), CACguaucga (SEQ ID NO: 1094), CACgucaguu (SEQ ID NO: 1095), CACgugagcu (SEQ ID NO: 1096), CACgugaguc (SEQ ID NO: 1097), CACgugagug (SEQ ID NO: 1098), CAGgcaagaa (SEQ ID NO: 1099), CAGgcaagac (SEQ ID NO: 1100), CAGgcaagag (SEQ ID NO: 1101), CAGgcaagga (SEQ ID NO: 1102), CAGgcaagua (SEQ ID NO: 1103), CAGgcaagug (SEQ ID NO: 1104), CAGgcaaguu (SEQ ID NO: 1105), CAGgcacgca (SEQ ID NO: 1106), CAGgcagagg (SEQ ID NO: 1107), CAGgcaggug (SEQ ID NO: 1108), CAGgcaucau (SEQ ID NO: 1109), CAGgcaugaa (SEQ ID NO: 1110), CAGgcaugag (SEQ ID NO: 1111), CAGgcaugca (SEQ ID NO: 1112), CAGgcaugcg (SEQ ID NO: 1113), CAGgcaugug (SEQ ID NO: 1114), CAGgcgagag (SEQ ID NO: 1115), CAGgcgccug (SEQ ID NO: 1116), CAGgcgugug (SEQ ID NO: 1117), CAGguaaaaa (SEQ ID NO: 1118), CAGguaaaag (SEQ ID NO: 1119), CAGguaaaca (SEQ ID NO: 1120), CAGguaaacc (SEQ ID NO: 1121), CAGguaaaga (SEQ ID NO: 1122), CAGguaaagc (SEQ ID NO: 1123), CAGguaaagu (SEQ ID NO: 1124), CAGguaaaua (SEQ ID NO: 1125), CAGguaaauc (SEQ ID NO: 1126), CAGguaaaug (SEQ ID NO: 1127), CAGguaaauu (SEQ ID NO: 1128), CAGguaacag (SEQ ID NO: 1129), CAGguaacau (SEQ ID NO: 1130), CAGguaacca (SEQ ID NO: 1131), CAGguaaccg (SEQ ID NO: 1132), CAGguaacgu (SEQ ID NO: 1133), CAGguaacua (SEQ ID NO: 1134), CAGguaacuc (SEQ ID NO: 1135), CAGguaacug (SEQ ID NO: 1136), CAGguaacuu (SEQ ID NO: 1137), CAGguaagaa (SEQ ID NO: 1138), CAGguaagac (SEQ ID NO: 1139), CAGguaagag (SEQ ID NO: 1140), CAGguaagau (SEQ ID NO: 1141), CAGguaagcc (SEQ ID NO: 1142), CAGguaagga (SEQ ID NO: 1143), CAGguaaggc (SEQ ID NO: 1144), CAGguaaggg (SEQ ID NO: 1145), CAGguaaggu (SEQ ID NO: 1146), CAGguaagua (SEQ ID NO: 1147), CAGguaagug (SEQ ID NO: 1148), CAGguaaguu (SEQ ID NO: 1149), CAGguaauaa (SEQ ID NO: 1150), CAGguaauau (SEQ ID NO: 1151), CAGguaaucc (SEQ ID NO: 1152), CAGguaaugc (SEQ ID NO: 1153), CAGguaaugg (SEQ ID NO: 1154), CAGguaaugu (SEQ ID NO: 1155), CAGguaauua (SEQ ID NO: 1156), CAGguaauuc (SEQ ID NO: 1157), CAGguaauug (SEQ ID NO: 1158), CAGguaauuu (SEQ ID NO: 1159), CAGguacaaa (SEQ ID NO: 1160), CAGguacaag (SEQ ID NO: 1161), CAGguacaau (SEQ ID NO: 1162), CAGguacaca (SEQ ID NO: 1163), CAGguacacg (SEQ ID NO: 1164), CAGguacaga (SEQ ID NO: 1165), CAGguacagg (SEQ ID NO: 1166), CAGguacagu (SEQ ID NO: 1167), CAGguacaua (SEQ ID NO: 1168), CAGguacaug (SEQ ID NO: 1169), CAGguacauu (SEQ ID NO: 1170), CAGguaccac (SEQ ID NO: 1171), CAGguaccca (SEQ ID NO: 1172), CAGguacccg (SEQ ID NO: 1173), CAGguacccu (SEQ ID NO: 1174), CAGguaccgc (SEQ ID NO: 1175), CAGguaccgg (SEQ ID NO: 1176), CAGguaccuc (SEQ ID NO: 1177), CAGguaccug (SEQ ID NO: 1178), CAGguaccuu (SEQ ID NO: 1179), CAGguacgag (SEQ ID NO: 1180), CAGguacgca (SEQ ID NO: 1181), CAGguacgcc (SEQ ID NO: 1182), CAGguacggu (SEQ ID NO: 1183), CAGguacgua (SEQ ID NO: 1184), CAGguacgug (SEQ ID NO: 1185), CAGguacuaa (SEQ ID NO: 1186), CAGguacuag (SEQ ID NO: 1187), CAGguacuau (SEQ ID NO: 1188), CAGguacucc (SEQ ID NO: 1189), CAGguacucu (SEQ ID NO: 1190), CAGguacuga (SEQ ID NO: 1191), CAGguacugc (SEQ ID NO: 1192), CAGguacugu (SEQ ID NO: 1193), CAGguacuua (SEQ ID NO: 1194), CAGguacuuu (SEQ ID NO: 1195), CAGguagaaa (SEQ ID NO: 1196), CAGguagaac (SEQ ID NO: 1197), CAGguagaag (SEQ ID NO: 1198), CAGguagaca (SEQ ID NO: 1199), CAGguagacc (SEQ ID NO: 1200), CAGguagaga (SEQ ID NO: 1201), CAGguagauu (SEQ ID NO: 1202), CAGguagcaa (SEQ ID NO: 1203), CAGguagcac (SEQ ID NO: 1204), CAGguagcag (SEQ ID NO: 1205), CAGguagcca (SEQ ID NO: 1206), CAGguagcgu (SEQ ID NO: 1207), CAGguagcua (SEQ ID NO: 1208), CAGguagcuc (SEQ ID NO: 1209), CAGguagcug (SEQ ID NO: 1210), CAGguagcuu (SEQ ID NO: 1211), CAGguaggaa (SEQ ID NO: 1212), CAGguaggac (SEQ ID NO: 1213), CAGguaggag (SEQ ID NO: 1214), CAGguaggca (SEQ ID NO: 1215), CAGguaggga (SEQ ID NO: 1216), CAGguagggc (SEQ ID NO: 1217), CAGguagggg (SEQ ID NO: 1218), CAGguagggu (SEQ ID NO: 1219), CAGguaggua (SEQ ID NO: 1220), CAGguagguc (SEQ ID NO: 1221), CAGguaggug (SEQ ID NO: 1222), CAGguagguu (SEQ ID NO: 1223), CAGguaguaa (SEQ ID NO: 1224), CAGguaguau (SEQ ID NO: 1225), CAGguaguca (SEQ ID NO: 1226), CAGguagucc (SEQ ID NO: 1227), CAGguaguga (SEQ ID NO: 1228), CAGguagugu (SEQ ID NO: 1229), CAGguaguuc (SEQ ID NO: 1230), CAGguaguug (SEQ ID NO: 1231), CAGguaguuu (SEQ ID NO: 1232), CAGguauaag (SEQ ID NO: 1233), CAGguauaca (SEQ ID NO: 1234), CAGguauaga (SEQ ID NO: 1235), CAGguauauc (SEQ ID NO: 1236), CAGguauaug (SEQ ID NO: 1237), CAGguauauu (SEQ ID NO: 1238), CAGguaucag (SEQ ID NO: 1239), CAGguaucau (SEQ ID NO: 1240), CAGguauccu (SEQ ID NO: 1241), CAGguaucga (SEQ ID NO: 1242), CAGguaucgc (SEQ ID NO: 1243), CAGguaucua (SEQ ID NO: 1244), CAGguaucug (SEQ ID NO: 1245), CAGguaucuu (SEQ ID NO: 1246), CAGguaugaa (SEQ ID NO: 1247), CAGguaugac (SEQ ID NO: 1248), CAGguaugag (SEQ ID NO: 1249), CAGguaugau (SEQ ID NO: 1250), CAGguaugca (SEQ ID NO: 1251), CAGguaugcc (SEQ ID NO: 1252), CAGguaugcg (SEQ ID NO: 1253), CAGguaugcu (SEQ ID NO: 1254), CAGguaugga (SEQ ID NO: 1255), CAGguauggg (SEQ ID NO: 1256), CAGguauggu (SEQ ID NO: 1257), CAGguaugua (SEQ ID NO: 1258), CAGguauguc (SEQ ID NO: 1259), CAGguaugug (SEQ ID NO: 1260), CAGguauguu (SEQ ID NO: 1261), CAGguauuau (SEQ ID NO: 1262), CAGguauuca (SEQ ID NO: 1263), CAGguauucu (SEQ ID NO: 1264), CAGguauuga (SEQ ID NO: 1265), CAGguauugg (SEQ ID NO: 1266), CAGguauugu (SEQ ID NO: 1267), CAGguauuua (SEQ ID NO: 1268), CAGguauuuc (SEQ ID NO: 1269), CAGguauuug (SEQ ID NO: 1270), CAGguauuuu (SEQ ID NO: 1271), CAGgucaaca (SEQ ID NO: 1272), CAGgucaaug (SEQ ID NO: 1273), CAGgucacgu (SEQ ID NO: 1274), CAGgucagaa (SEQ ID NO: 1275), CAGgucagac (SEQ ID NO: 1276), CAGgucagca (SEQ ID NO: 1277), CAGgucagcc (SEQ ID NO: 1278), CAGgucagcg (SEQ ID NO: 1279), CAGgucagga (SEQ ID NO: 1280), CAGgucagua (SEQ ID NO: 1281), CAGgucaguc (SEQ ID NO: 1282), CAGgucagug (SEQ ID NO: 1283), CAGgucaguu (SEQ ID NO: 1284), CAGgucaucc (SEQ ID NO: 1285), CAGgucaugc (SEQ ID NO: 1286), CAGgucauua (SEQ ID NO: 1287), CAGgucauuu (SEQ ID NO: 1288), CAGguccacc (SEQ ID NO: 1289), CAGguccacu (SEQ ID NO: 1290), CAGguccagu (SEQ ID NO: 1291), CAGguccauc (SEQ ID NO: 1292), CAGguccauu (SEQ ID NO: 1293), CAGgucccag (SEQ ID NO: 1294), CAGgucccug (SEQ ID NO: 1295), CAGguccuga (SEQ ID NO: 1296), CAGguccugc (SEQ ID NO: 1297), CAGguccugg (SEQ ID NO: 1298), CAGgucggcc (SEQ ID NO: 1299), CAGgucggug (SEQ ID NO: 1300), CAGgucguug (SEQ ID NO: 1301), CAGgucucuc (SEQ ID NO: 1302), CAGgucucuu (SEQ ID NO: 1303), CAGgucugag (SEQ ID NO: 1304), CAGgucugcc (SEQ ID NO: 1305), CAGgucugcg (SEQ ID NO: 1306), CAGgucugga (SEQ ID NO: 1307), CAGgucuggu (SEQ ID NO: 1308), CAGgucugua (SEQ ID NO: 1309), CAGgucuguc (SEQ ID NO: 1310), CAGgucugug (SEQ ID NO: 1311), CAGgucuguu (SEQ ID NO: 1312), CAGgucuucc (SEQ ID NO: 1313), CAGgucuuuc (SEQ ID NO: 1314), CAGgugaaag (SEQ ID NO: 1315), CAGgugaaau (SEQ ID NO: 1316), CAGgugaaca (SEQ ID NO: 1317), CAGgugaaga (SEQ ID NO: 1318), CAGgugaagg (SEQ ID NO: 1319), CAGgugaaua (SEQ ID NO: 1320), CAGgugaauc (SEQ ID NO: 1321), CAGgugaauu (SEQ ID NO: 1322), CAGgugacaa (SEQ ID NO: 1323), CAGgugacau (SEQ ID NO: 1324), CAGgugacca (SEQ ID NO: 1325), CAGgugaccc (SEQ ID NO: 1326), CAGgugaccg (SEQ ID NO: 1327), CAGgugaccu (SEQ ID NO: 1328), CAGgugacgg (SEQ ID NO: 1329), CAGgugacua (SEQ ID NO: 1330), CAGgugacuc (SEQ ID NO: 1331), CAGgugacug (SEQ ID NO: 1332), CAGgugagaa (SEQ ID NO: 1333), CAGgugagac (SEQ ID NO: 1334), CAGgugagag (SEQ ID NO: 1335), CAGgugagau (SEQ ID NO: 1336), CAGgugagca (SEQ ID NO: 1337), CAGgugagcc (SEQ ID NO: 1338), CAGgugagcg (SEQ ID NO: 1339), CAGgugagcu (SEQ ID NO: 1340), CAGgugagga (SEQ ID NO: 1341), CAGgugaggc (SEQ ID NO: 1342), CAGgugaggg (SEQ ID NO: 1343), CAGgugaggu (SEQ ID NO: 1344), CAGgugagua (SEQ ID NO: 1345), CAGgugaguc (SEQ ID NO: 1346), CAGgugagug (SEQ ID NO: 1347), CAGgugaguu (SEQ ID NO: 1348), CAGgugauaa (SEQ ID NO: 1349), CAGgugaucc (SEQ ID NO: 1350), CAGgugaucu (SEQ ID NO: 1351), CAGgugaugc (SEQ ID NO: 1352), CAGgugaugg (SEQ ID NO: 1353), CAGgugaugu (SEQ ID NO: 1354), CAGgugauua (SEQ ID NO: 1355), CAGgugauuc (SEQ ID NO: 1356), CAGgugauug (SEQ ID NO: 1357), CAGgugauuu (SEQ ID NO: 1358), CAGgugcaaa (SEQ ID NO: 1359), CAGgugcaag (SEQ ID NO: 1360), CAGgugcaca (SEQ ID NO: 1361), CAGgugcacg (SEQ ID NO: 1362), CAGgugcaga (SEQ ID NO: 1363), CAGgugcagg (SEQ ID NO: 1364), CAGgugcaua (SEQ ID NO: 1365), CAGgugcauc (SEQ ID NO: 1366), CAGgugcaug (SEQ ID NO: 1367), CAGgugccaa (SEQ ID NO: 1368), CAGgugccca (SEQ ID NO: 1369), CAGgugcccc (SEQ ID NO: 1370), CAGgugcccg (SEQ ID NO: 1371), CAGgugccua (SEQ ID NO: 1372), CAGgugccug (SEQ ID NO: 1373), CAGgugcgaa (SEQ ID NO: 1374), CAGgugcgca (SEQ ID NO: 1375), CAGgugcgcc (SEQ ID NO: 1376), CAGgugcgcg (SEQ ID NO: 1377), CAGgugcgga (SEQ ID NO: 1378), CAGgugcggu (SEQ ID NO: 1379), CAGgugcgua (SEQ ID NO: 1380), CAGgugcguc (SEQ ID NO: 1381), CAGgugcgug (SEQ ID NO: 1382), CAGgugcuag (SEQ ID NO: 1383), CAGgugcuau (SEQ ID NO: 1384), CAGgugcuca (SEQ ID NO: 1385), CAGgugcucc (SEQ ID NO: 1386), CAGgugcucg (SEQ ID NO: 1387), CAGgugcugc (SEQ ID NO: 1388), CAGgugcugg (SEQ ID NO: 1389), CAGgugcuua (SEQ ID NO: 1390), CAGgugcuuc (SEQ ID NO: 1391), CAGgugcuug (SEQ ID NO: 1392), CAGguggaac (SEQ ID NO: 1393), CAGguggaag (SEQ ID NO: 1394), CAGguggaau (SEQ ID NO: 1395), CAGguggaga (SEQ ID NO: 1396), CAGguggagu (SEQ ID NO: 1397), CAGguggauu (SEQ ID NO: 1398), CAGguggcca (SEQ ID NO: 1399), CAGguggcuc (SEQ ID NO: 1400), CAGguggcug (SEQ ID NO: 1401), CAGgugggaa (SEQ ID NO: 1402), CAGgugggac (SEQ ID NO: 1403), CAGgugggag (SEQ ID NO: 1404), CAGgugggau (SEQ ID NO: 1405), CAGgugggca (SEQ ID NO: 1406), CAGgugggcc (SEQ ID NO: 1407), CAGgugggcu (SEQ ID NO: 1408), CAGgugggga (SEQ ID NO: 1409), CAGguggggc (SEQ ID NO: 1410), CAGguggggg (SEQ ID NO: 1411), CAGguggggu (SEQ ID NO: 1412), CAGgugggua (SEQ ID NO: 1413), CAGguggguc (SEQ ID NO: 1414), CAGgugggug (SEQ ID NO: 1415), CAGguggguu (SEQ ID NO: 1416), CAGguggucu (SEQ ID NO: 1417), CAGguggugg (SEQ ID NO: 1418), CAGgugguug (SEQ ID NO: 1419), CAGguguaca (SEQ ID NO: 1420), CAGguguagg (SEQ ID NO: 1421), CAGguguauc (SEQ ID NO: 1422), CAGgugucac (SEQ ID NO: 1423), CAGgugucag (SEQ ID NO: 1424), CAGgugucca (SEQ ID NO: 1425), CAGguguccu (SEQ ID NO: 1426), CAGgugucua (SEQ ID NO: 1427), CAGgugucuc (SEQ ID NO: 1428), CAGgugucug (SEQ ID NO: 1429), CAGgugugaa (SEQ ID NO: 1430), CAGgugugac (SEQ ID NO: 1431), CAGgugugag (SEQ ID NO: 1432), CAGgugugau (SEQ ID NO: 1433), CAGgugugca (SEQ ID NO: 1434), CAGgugugcc (SEQ ID NO: 1435), CAGgugugcg (SEQ ID NO: 1436), CAGgugugcu (SEQ ID NO: 1437), CAGgugugga (SEQ ID NO: 1438), CAGguguggc (SEQ ID NO: 1439), CAGgugugua (SEQ ID NO: 1440), CAGguguguc (SEQ ID NO: 1441), CAGgugugug (SEQ ID NO: 1442), CAGguguguu (SEQ ID NO: 1443), CAGguguuua (SEQ ID NO: 1444), CAGguuaaaa (SEQ ID NO: 1445), CAGguuaaua (SEQ ID NO: 1446), CAGguuaauc (SEQ ID NO: 1447), CAGguuaccu (SEQ ID NO: 1448), CAGguuagaa (SEQ ID NO: 1449), CAGguuagag (SEQ ID NO: 1450), CAGguuagau (SEQ ID NO: 1451), CAGguuagcc (SEQ ID NO: 1452), CAGguuaggg (SEQ ID NO: 1453), CAGguuaggu (SEQ ID NO: 1454), CAGguuagua (SEQ ID NO: 1455), CAGguuaguc (SEQ ID NO: 1456), CAGguuagug (SEQ ID NO: 1457), CAGguuaguu (SEQ ID NO: 1458), CAGguuauca (SEQ ID NO: 1459), CAGguuaugu (SEQ ID NO: 1460), CAGguuauua (SEQ ID NO: 1461), CAGguuauug (SEQ ID NO: 1462), CAGguucaaa (SEQ ID NO: 1463), CAGguucaac (SEQ ID NO: 1464), CAGguucaag (SEQ ID NO: 1465), CAGguucaca (SEQ ID NO: 1466), CAGguucacg (SEQ ID NO: 1467), CAGguucagg (SEQ ID NO: 1468), CAGguucaug (SEQ ID NO: 1469), CAGguuccag (SEQ ID NO: 1470), CAGguuccca (SEQ ID NO: 1471), CAGguucccg (SEQ ID NO: 1472), CAGguucgaa (SEQ ID NO: 1473), CAGguucgag (SEQ ID NO: 1474), CAGguucuau (SEQ ID NO: 1475), CAGguucugc (SEQ ID NO: 1476), CAGguucuua (SEQ ID NO: 1477), CAGguucuuc (SEQ ID NO: 1478), CAGguucuuu (SEQ ID NO: 1479), CAGguugaac (SEQ ID NO: 1480), CAGguugaag (SEQ ID NO: 1481), CAGguugagu (SEQ ID NO: 1482), CAGguugaua (SEQ ID NO: 1483), CAGguuggag (SEQ ID NO: 1484), CAGguuggca (SEQ ID NO: 1485), CAGguuggcc (SEQ ID NO: 1486), CAGguugguc (SEQ ID NO: 1487), CAGguuggug (SEQ ID NO: 1488), CAGguugguu (SEQ ID NO: 1489), CAGguuguaa (SEQ ID NO: 1490), CAGguuguac (SEQ ID NO: 1491), CAGguuguau (SEQ ID NO: 1492), CAGguuguca (SEQ ID NO: 1493), CAGguuguga (SEQ ID NO: 1494), CAGguuguug (SEQ ID NO: 1495), CAGguuuaag (SEQ ID NO: 1496), CAGguuuacc (SEQ ID NO: 1497), CAGguuuagc (SEQ ID NO: 1498), CAGguuuagu (SEQ ID NO: 1499), CAGguuucuu (SEQ ID NO: 1500), CAGguuugaa (SEQ ID NO: 1501), CAGguuugag (SEQ ID NO: 1502), CAGguuugau (SEQ ID NO: 1503), CAGguuugcc (SEQ ID NO: 1504), CAGguuugcu (SEQ ID NO: 1505), CAGguuuggg (SEQ ID NO: 1506), CAGguuuggu (SEQ ID NO: 1507), CAGguuugua (SEQ ID NO: 1508), CAGguuugug (SEQ ID NO: 1509), CAGguuuguu (SEQ ID NO: 1510), CAGguuuucu (SEQ ID NO: 1511), CAGguuuugg (SEQ ID NO: 1512), CAGguuuuuc (SEQ ID NO: 1513), CAGguuuuuu (SEQ ID NO: 1514), CAUgcagguu (SEQ ID NO: 1515), CAUguaaaac (SEQ ID NO: 1516), CAUguaacua (SEQ ID NO: 1517), CAUguaagaa (SEQ ID NO: 1518), CAUguaagag (SEQ ID NO: 1519), CAUguaagau (SEQ ID NO: 1520), CAUguaagcc (SEQ ID NO: 1521), CAUguaagua (SEQ ID NO: 1522), CAUguaagug (SEQ ID NO: 1523), CAUguaaguu (SEQ ID NO: 1524), CAUguaauua (SEQ ID NO: 1525), CAUguacaua (SEQ ID NO: 1526), CAUguaccac (SEQ ID NO: 1527), CAUguacguu (SEQ ID NO: 1528), CAUguaggua (SEQ ID NO: 1529), CAUguaggug (SEQ ID NO: 1530), CAUguagguu (SEQ ID NO: 1531), CAUguaugaa (SEQ ID NO: 1532), CAUguaugua (SEQ ID NO: 1533), CAUguaugug (SEQ ID NO: 1534), CAUguauguu (SEQ ID NO: 1535), CAUgugagaa (SEQ ID NO: 1536), CAUgugagca (SEQ ID NO: 1537), CAUgugagcu (SEQ ID NO: 1538), CAUgugagua (SEQ ID NO: 1539), CAUgugaguc (SEQ ID NO: 1540), CAUgugagug (SEQ ID NO: 1541), CAUgugaguu (SEQ ID NO: 1542), CAUgugcgua (SEQ ID NO: 1543), CAUgugggaa (SEQ ID NO: 1544), CAUguggguu (SEQ ID NO: 1545), CAUgugugug (SEQ ID NO: 1546), CAUguguguu (SEQ ID NO: 1547), CAUguuaaua (SEQ ID NO: 1548), CAUguuagcc (SEQ ID NO: 1549), CCAguaagau (SEQ ID NO: 1550), CCAguaagca (SEQ ID NO: 1551), CCAguaagcc (SEQ ID NO: 1552), CCAguaagcu (SEQ ID NO: 1553), CCAguaagga (SEQ ID NO: 1554), CCAguaagua (SEQ ID NO: 1555), CCAguaaguc (SEQ ID NO: 1556), CCAguaagug (SEQ ID NO: 1557), CCAguaaguu (SEQ ID NO: 1558), CCAguaauug (SEQ ID NO: 1559), CCAguacggg (SEQ ID NO: 1560), CCAguagguc (SEQ ID NO: 1561), CCAguauugu (SEQ ID NO: 1562), CCAgugaggc (SEQ ID NO: 1563), CCAgugagua (SEQ ID NO: 1564), CCAgugagug (SEQ ID NO: 1565), CCAguggguc (SEQ ID NO: 1566), CCAguuaguu (SEQ ID NO: 1567), CCAguugagu (SEQ ID NO: 1568), CCCguaagau (SEQ ID NO: 1569), CCCguauguc (SEQ ID NO: 1570), CCCguauguu (SEQ ID NO: 1571), CCCguccugc (SEQ ID NO: 1572), CCCgugagug (SEQ ID NO: 1573), CCGguaaaga (SEQ ID NO: 1574), CCGguaagau (SEQ ID NO: 1575), CCGguaagcc (SEQ ID NO: 1576), CCGguaagga (SEQ ID NO: 1577), CCGguaaggc (SEQ ID NO: 1578), CCGguaaugg (SEQ ID NO: 1579), CCGguacagu (SEQ ID NO: 1580), CCGguacuga (SEQ ID NO: 1581), CCGguauucc (SEQ ID NO: 1582), CCGgucagug (SEQ ID NO: 1583), CCGgugaaaa (SEQ ID NO: 1584), CCGgugagaa (SEQ ID NO: 1585), CCGgugaggg (SEQ ID NO: 1586), CCGgugagug (SEQ ID NO: 1587), CCGgugaguu (SEQ ID NO: 1588), CCGgugcgcg (SEQ ID NO: 1589), CCGgugggcg (SEQ ID NO: 1590), CCGguugguc (SEQ ID NO: 1591), CCUguaaaug (SEQ ID NO: 1592), CCUguaaauu (SEQ ID NO: 1593), CCUguaagaa (SEQ ID NO: 1594), CCUguaagac (SEQ ID NO: 1595), CCUguaagag (SEQ ID NO: 1596), CCUguaagca (SEQ ID NO: 1597), CCUguaagcg (SEQ ID NO: 1598), CCUguaagga (SEQ ID NO: 1599), CCUguaaguu (SEQ ID NO: 1600), CCUguaggua (SEQ ID NO: 1601), CCUguaggug (SEQ ID NO: 1602), CCUguaucuu (SEQ ID NO: 1603), CCUguauggu (SEQ ID NO: 1604), CCUguaugug (SEQ ID NO: 1605), CCUgugagaa (SEQ ID NO: 1606), CCUgugagca (SEQ ID NO: 1607), CCUgugaggg (SEQ ID NO: 1608), CCUgugaguc (SEQ ID NO: 1609), CCUgugagug (SEQ ID NO: 1610), CCUgugaguu (SEQ ID NO: 1611), CCUguggcuc (SEQ ID NO: 1612), CCUgugggua (SEQ ID NO: 1613), CCUgugugua (SEQ ID NO: 1614), CCUguuagaa (SEQ ID NO: 1615), CGAguaaggg (SEQ ID NO: 1616), CGAguaaggu (SEQ ID NO: 1617), CGAguagcug (SEQ ID NO: 1618), CGAguaggug (SEQ ID NO: 1619), CGAguagguu (SEQ ID NO: 1620), CGAgugagca (SEQ ID NO: 1621), CGCguaagag (SEQ ID NO: 1622), CGGgcaggca (SEQ ID NO: 1623), CGGguaagcc (SEQ ID NO: 1624), CGGguaagcu (SEQ ID NO: 1625), CGGguaaguu (SEQ ID NO: 1626), CGGguaauuc (SEQ ID NO: 1627), CGGguaauuu (SEQ ID NO: 1628), CGGguacagu (SEQ ID NO: 1629), CGGguacggg (SEQ ID NO: 1630), CGGguaggag (SEQ ID NO: 1631), CGGguaggcc (SEQ ID NO: 1632), CGGguaggug (SEQ ID NO: 1633), CGGguauuua (SEQ ID NO: 1634), CGGgucugag (SEQ ID NO: 1635), CGGgugaccg (SEQ ID NO: 1636), CGGgugacuc (SEQ ID NO: 1637), CGGgugagaa (SEQ ID NO: 1638), CGGgugaggg (SEQ ID NO: 1639), CGGgugaggu (SEQ ID NO: 1640), CGGgugagua (SEQ ID NO: 1641), CGGgugagug (SEQ ID NO: 1642), CGGgugaguu (SEQ ID NO: 1643), CGGgugauuu (SEQ ID NO: 1644), CGGgugccuu (SEQ ID NO: 1645), CGGgugggag (SEQ ID NO: 1646), CGGgugggug (SEQ ID NO: 1647), CGGguggguu (SEQ ID NO: 1648), CGGguguguc (SEQ ID NO: 1649), CGGgugugug (SEQ ID NO: 1650), CGGguguguu (SEQ ID NO: 1651), CGGguucaag (SEQ ID NO: 1652), CGGguucaug (SEQ ID NO: 1653), CGGguuugcu (SEQ ID NO: 1654), CGUguagggu (SEQ ID NO: 1655), CGUguaugca (SEQ ID NO: 1656), CGUguaugua (SEQ ID NO: 1657), CGUgucugua (SEQ ID NO: 1658), CGUgugagug (SEQ ID NO: 1659), CGUguuuucu (SEQ ID NO: 1660), CUAguaaaug (SEQ ID NO: 1661), CUAguaagcg (SEQ ID NO: 1662), CUAguaagcu (SEQ ID NO: 1663), CUAguaagua (SEQ ID NO: 1664), CUAguaaguc (SEQ ID NO: 1665), CUAguaagug (SEQ ID NO: 1666), CUAguaaguu (SEQ ID NO: 1667), CUAguaauuu (SEQ ID NO: 1668), CUAguaggua (SEQ ID NO: 1669), CUAguagguu (SEQ ID NO: 1670), CUAguaugua (SEQ ID NO: 1671), CUAguauguu (SEQ ID NO: 1672), CUAgugagua (SEQ ID NO: 1673), CUCguaagca (SEQ ID NO: 1674), CUCguaagug (SEQ ID NO: 1675), CUCguaaguu (SEQ ID NO: 1676), CUCguaucug (SEQ ID NO: 1677), CUCgucugug (SEQ ID NO: 1678), CUCgugaaua (SEQ ID NO: 1679), CUCgugagua (SEQ ID NO: 1680), CUCgugauua (SEQ ID NO: 1681), CUGguaaaaa (SEQ ID NO: 1682), CUGguaaaau (SEQ ID NO: 1683), CUGguaaacc (SEQ ID NO: 1684), CUGguaaacg (SEQ ID NO: 1685), CUGguaaagc (SEQ ID NO: 1686), CUGguaaaua (SEQ ID NO: 1687), CUGguaaauc (SEQ ID NO: 1688), CUGguaaaug (SEQ ID NO: 1689), CUGguaaauu (SEQ ID NO: 1690), CUGguaacac (SEQ ID NO: 1691), CUGguaacag (SEQ ID NO: 1692), CUGguaaccc (SEQ ID NO: 1693), CUGguaaccg (SEQ ID NO: 1694), CUGguaacug (SEQ ID NO: 1695), CUGguaacuu (SEQ ID NO: 1696), CUGguaagaa (SEQ ID NO: 1697), CUGguaagag (SEQ ID NO: 1698), CUGguaagau (SEQ ID NO: 1699), CUGguaagca (SEQ ID NO: 1700), CUGguaagcc (SEQ ID NO: 1701), CUGguaagcu (SEQ ID NO: 1702), CUGguaagga (SEQ ID NO: 1703), CUGguaaggc (SEQ ID NO: 1704), CUGguaaggg (SEQ ID NO: 1705), CUGguaaggu (SEQ ID NO: 1706), CUGguaagua (SEQ ID NO: 1707), CUGguaagug (SEQ ID NO: 1708), CUGguaaguu (SEQ ID NO: 1709), CUGguaauga (SEQ ID NO: 1710), CUGguaaugc (SEQ ID NO: 1711), CUGguaauuc (SEQ ID NO: 1712), CUGguaauuu (SEQ ID NO: 1713), CUGguacaac (SEQ ID NO: 1714), CUGguacaau (SEQ ID NO: 1715), CUGguacaga (SEQ ID NO: 1716), CUGguacaua (SEQ ID NO: 1717), CUGguacauu (SEQ ID NO: 1718), CUGguaccau (SEQ ID NO: 1719), CUGguacguu (SEQ ID NO: 1720), CUGguacuaa (SEQ ID NO: 1721), CUGguacuug (SEQ ID NO: 1722), CUGguacuuu (SEQ ID NO: 1723), CUGguagaga (SEQ ID NO: 1724), CUGguagaua (SEQ ID NO: 1725), CUGguagcgu (SEQ ID NO: 1726), CUGguaggau (SEQ ID NO: 1727), CUGguaggca (SEQ ID NO: 1728), CUGguaggua (SEQ ID NO: 1729), CUGguagguc (SEQ ID NO: 1730), CUGguaggug (SEQ ID NO: 1731), CUGguaucaa (SEQ ID NO: 1732), CUGguaugau (SEQ ID NO: 1733), CUGguauggc (SEQ ID NO: 1734), CUGguauggu (SEQ ID NO: 1735), CUGguaugua (SEQ ID NO: 1736), CUGguaugug (SEQ ID NO: 1737), CUGguauguu (SEQ ID NO: 1738), CUGguauuga (SEQ ID NO: 1739), CUGguauuuc (SEQ ID NO: 1740), CUGguauuuu (SEQ ID NO: 1741), CUGgucaaca (SEQ ID NO: 1742), CUGgucagag (SEQ ID NO: 1743), CUGgucccgc (SEQ ID NO: 1744), CUGgucggua (SEQ ID NO: 1745), CUGgucuggg (SEQ ID NO: 1746), CUGgugaagu (SEQ ID NO: 1747), CUGgugaaua (SEQ ID NO: 1748), CUGgugaauu (SEQ ID NO: 1749), CUGgugacua (SEQ ID NO: 1750), CUGgugagaa (SEQ ID NO: 1751), CUGgugagac (SEQ ID NO: 1752), CUGgugagca (SEQ ID NO: 1753), CUGgugagcu (SEQ ID NO: 1754), CUGgugagga (SEQ ID NO: 1755), CUGgugaggc (SEQ ID NO: 1756), CUGgugaggg (SEQ ID NO: 1757), CUGgugaggu (SEQ ID NO: 1758), CUGgugagua (SEQ ID NO: 1759), CUGgugaguc (SEQ ID NO: 1760), CUGgugagug (SEQ ID NO: 1761), CUGgugaguu (SEQ ID NO: 1762), CUGgugauua (SEQ ID NO: 1763), CUGgugauuu (SEQ ID NO: 1764), CUGgugcaga (SEQ ID NO: 1765), CUGgugcgcu (SEQ ID NO: 1766), CUGgugcgug (SEQ ID NO: 1767), CUGgugcuga (SEQ ID NO: 1768), CUGgugggag (SEQ ID NO: 1769), CUGgugggga (SEQ ID NO: 1770), CUGgugggua (SEQ ID NO: 1771), CUGguggguc (SEQ ID NO: 1772), CUGgugggug (SEQ ID NO: 1773), CUGguggguu (SEQ ID NO: 1774), CUGgugugaa (SEQ ID NO: 1775), CUGgugugca (SEQ ID NO: 1776), CUGgugugcu (SEQ ID NO: 1777), CUGguguggu (SEQ ID NO: 1778), CUGgugugug (SEQ ID NO: 1779), CUGguguguu (SEQ ID NO: 1780), CUGguuagcu (SEQ ID NO: 1781), CUGguuagug (SEQ ID NO: 1782), CUGguucgug (SEQ ID NO: 1783), CUGguuggcu (SEQ ID NO: 1784), CUGguuguuu (SEQ ID NO: 1785), CUGguuugua (SEQ ID NO: 1786), CUGguuuguc (SEQ ID NO: 1787), CUGguuugug (SEQ ID NO: 1788), CUUguaaaug (SEQ ID NO: 1789), CUUguaagcu (SEQ ID NO: 1790), CUUguaagga (SEQ ID NO: 1791), CUUguaaggc (SEQ ID NO: 1792), CUUguaagua (SEQ ID NO: 1793), CUUguaagug (SEQ ID NO: 1794), CUUguaaguu (SEQ ID NO: 1795), CUUguacguc (SEQ ID NO: 1796), CUUguacgug (SEQ ID NO: 1797), CUUguaggua (SEQ ID NO: 1798), CUUguagugc (SEQ ID NO: 1799), CUUguauagg (SEQ ID NO: 1800), CUUgucagua (SEQ ID NO: 1801), CUUgugagua (SEQ ID NO: 1802), CUUgugaguc (SEQ ID NO: 1803), CUUgugaguu (SEQ ID NO: 1804), CUUguggguu (SEQ ID NO: 1805), CUUgugugua (SEQ ID NO: 1806), CUUguuagug (SEQ ID NO: 1807), CUUguuugag (SEQ ID NO: 1808), GAAguaaaac (SEQ ID NO: 1809), GAAguaaagc (SEQ ID NO: 1810), GAAguaaagu (SEQ ID NO: 1811), GAAguaaaua (SEQ ID NO: 1812), GAAguaaauu (SEQ ID NO: 1813), GAAguaagaa (SEQ ID NO: 1814), GAAguaagcc (SEQ ID NO: 1815), GAAguaagcu (SEQ ID NO: 1816), GAAguaagga (SEQ ID NO: 1817), GAAguaagua (SEQ ID NO: 1818), GAAguaagug (SEQ ID NO: 1819), GAAguaaguu (SEQ ID NO: 1820), GAAguaauau (SEQ ID NO: 1821), GAAguaaugc (SEQ ID NO: 1822), GAAguaauua (SEQ ID NO: 1823), GAAguaauuu (SEQ ID NO: 1824), GAAguaccau (SEQ ID NO: 1825), GAAguacgua (SEQ ID NO: 1826), GAAguacguc (SEQ ID NO: 1827), GAAguaggca (SEQ ID NO: 1828), GAAguagguc (SEQ ID NO: 1829), GAAguauaaa (SEQ ID NO: 1830), GAAguaugcu (SEQ ID NO: 1831), GAAguaugug (SEQ ID NO: 1832), GAAguauguu (SEQ ID NO: 1833), GAAguauuaa (SEQ ID NO: 1834), GAAgucagug (SEQ ID NO: 1835), GAAgugagag (SEQ ID NO: 1836), GAAgugagcg (SEQ ID NO: 1837), GAAgugaggu (SEQ ID NO: 1838), GAAgugaguc (SEQ ID NO: 1839), GAAgugagug (SEQ ID NO: 1840), GAAgugaguu (SEQ ID NO: 1841), GAAgugauaa (SEQ ID NO: 1842), GAAgugauuc (SEQ ID NO: 1843), GAAgugcgug (SEQ ID NO: 1844), GAAguguggg (SEQ ID NO: 1845), GAAguguguc (SEQ ID NO: 1846), GAAguuggug (SEQ ID NO: 1847), GACguaaagu (SEQ ID NO: 1848), GACguaagcu (SEQ ID NO: 1849), GACguaagua (SEQ ID NO: 1850), GACguaaugg (SEQ ID NO: 1851), GACguaugcc (SEQ ID NO: 1852), GACguauguu (SEQ ID NO: 1853), GACgugagcc (SEQ ID NO: 1854), GACgugagug (SEQ ID NO: 1855), GAGgcaaaug (SEQ ID NO: 1856), GAGgcaagag (SEQ ID NO: 1857), GAGgcaagua (SEQ ID NO: 1858), GAGgcaagug (SEQ ID NO: 1859), GAGgcaaguu (SEQ ID NO: 1860), GAGgcacgag (SEQ ID NO: 1861), GAGgcaggga (SEQ ID NO: 1862), GAGgcaugug (SEQ ID NO: 1863), GAGgcgaagg (SEQ ID NO: 1864), GAGguaaaaa (SEQ ID NO: 1865), GAGguaaaac (SEQ ID NO: 1866), GAGguaaaag (SEQ ID NO: 1867), GAGguaaaau (SEQ ID NO: 1868), GAGguaaacc (SEQ ID NO: 1869), GAGguaaaga (SEQ ID NO: 1870), GAGguaaagc (SEQ ID NO: 1871), GAGguaaagu (SEQ ID NO: 1872), GAGguaaaua (SEQ ID NO: 1873), GAGguaaauc (SEQ ID NO: 1874), GAGguaaaug (SEQ ID NO: 1875), GAGguaaauu (SEQ ID NO: 1876), GAGguaacaa (SEQ ID NO: 1877), GAGguaacag (SEQ ID NO: 1878), GAGguaacca (SEQ ID NO: 1879), GAGguaaccu (SEQ ID NO: 1880), GAGguaacuu (SEQ ID NO: 1881), GAGguaagaa (SEQ ID NO: 1882), GAGguaagag (SEQ ID NO: 1883), GAGguaagau (SEQ ID NO: 1884), GAGguaagca (SEQ ID NO: 1885), GAGguaagcc (SEQ ID NO: 1886), GAGguaagcg (SEQ ID NO: 1887), GAGguaagcu (SEQ ID NO: 1888), GAGguaagga (SEQ ID NO: 1889), GAGguaaggc (SEQ ID NO: 1890), GAGguaaggg (SEQ ID NO: 1891), GAGguaaggu (SEQ ID NO: 1892), GAGguaagua (SEQ ID NO: 1893), GAGguaaguc (SEQ ID NO: 1894), GAGguaauaa (SEQ ID NO: 1895), GAGguaauac (SEQ ID NO: 1896), GAGguaauau (SEQ ID NO: 1897), GAGguaauca (SEQ ID NO: 1898), GAGguaaucu (SEQ ID NO: 1899), GAGguaaugg (SEQ ID NO: 1900), GAGguaaugu (SEQ ID NO: 1901), GAGguaauug (SEQ ID NO: 1902), GAGguaauuu (SEQ ID NO: 1903), GAGguacaaa (SEQ ID NO: 1904), GAGguacaac (SEQ ID NO: 1905), GAGguacaga (SEQ ID NO: 1906), GAGguacagc (SEQ ID NO: 1907), GAGguacagu (SEQ ID NO: 1908), GAGguacaua (SEQ ID NO: 1909), GAGguacauu (SEQ ID NO: 1910), GAGguaccag (SEQ ID NO: 1911), GAGguaccga (SEQ ID NO: 1912), GAGguaccug (SEQ ID NO: 1913), GAGguaccuu (SEQ ID NO: 1914), GAGguacuag (SEQ ID NO: 1915), GAGguacuau (SEQ ID NO: 1916), GAGguacucc (SEQ ID NO: 1917), GAGguacugc (SEQ ID NO: 1918), GAGguacugg (SEQ ID NO: 1919), GAGguacugu (SEQ ID NO: 1920), GAGguacuug (SEQ ID NO: 1921), GAGguacuuu (SEQ ID NO: 1922), GAGguagaag (SEQ ID NO: 1923), GAGguagaga (SEQ ID NO: 1924), GAGguagagg (SEQ ID NO: 1925), GAGguagagu (SEQ ID NO: 1926), GAGguagauc (SEQ ID NO: 1927), GAGguagcua (SEQ ID NO: 1928), GAGguagcug (SEQ ID NO: 1929), GAGguaggaa (SEQ ID NO: 1930), GAGguaggag (SEQ ID NO: 1931), GAGguaggca (SEQ ID NO: 1932), GAGguaggcu (SEQ ID NO: 1933), GAGguaggga (SEQ ID NO: 1934), GAGguagggc (SEQ ID NO: 1935), GAGguagggg (SEQ ID NO: 1936), GAGguaggua (SEQ ID NO: 1937), GAGguaggug (SEQ ID NO: 1938), GAGguagguu (SEQ ID NO: 1939), GAGguaguaa (SEQ ID NO: 1940), GAGguaguag (SEQ ID NO: 1941), GAGguaguau (SEQ ID NO: 1942), GAGguagucu (SEQ ID NO: 1943), GAGguagugc (SEQ ID NO: 1944), GAGguagugg (SEQ ID NO: 1945), GAGguaguua (SEQ ID NO: 1946), GAGguaguug (SEQ ID NO: 1947), GAGguauaag (SEQ ID NO: 1948), GAGguauacu (SEQ ID NO: 1949), GAGguauagc (SEQ ID NO: 1950), GAGguauaug (SEQ ID NO: 1951), GAGguauauu (SEQ ID NO: 1952), GAGguaucau (SEQ ID NO: 1953), GAGguaucug (SEQ ID NO: 1954), GAGguaucuu (SEQ ID NO: 1955), GAGguaugaa (SEQ ID NO: 1956), GAGguaugac (SEQ ID NO: 1957), GAGguaugag (SEQ ID NO: 1958), GAGguaugcc (SEQ ID NO: 1959), GAGguaugcg (SEQ ID NO: 1960), GAGguaugcu (SEQ ID NO: 1961), GAGguaugga (SEQ ID NO: 1962), GAGguauggg (SEQ ID NO: 1963), GAGguauggu (SEQ ID NO: 1964), GAGguaugua (SEQ ID NO: 1965), GAGguauguc (SEQ ID NO: 1966), GAGguaugug (SEQ ID NO: 1967), GAGguauguu (SEQ ID NO: 1968), GAGguauucc (SEQ ID NO: 1969), GAGguauuga (SEQ ID NO: 1970), GAGguauugu (SEQ ID NO: 1971), GAGguauuua (SEQ ID NO: 1972), GAGguauuuc (SEQ ID NO: 1973), GAGguauuug (SEQ ID NO: 1974), GAGguauuuu (SEQ ID NO: 1975), GAGgucaaca (SEQ ID NO: 1976), GAGgucaagg (SEQ ID NO: 1977), GAGgucaaug (SEQ ID NO: 1978), GAGgucacug (SEQ ID NO: 1979), GAGgucagaa (SEQ ID NO: 1980), GAGgucagag (SEQ ID NO: 1981), GAGgucagcu (SEQ ID NO: 1982), GAGgucagga (SEQ ID NO: 1983), GAGgucaggc (SEQ ID NO: 1984), GAGgucaggg (SEQ ID NO: 1985), GAGgucaggu (SEQ ID NO: 1986), GAGgucagua (SEQ ID NO: 1987), GAGgucauau (SEQ ID NO: 1988), GAGgucaugu (SEQ ID NO: 1989), GAGgucauuu (SEQ ID NO: 1990), GAGguccaua (SEQ ID NO: 1991), GAGguccauc (SEQ ID NO: 1992), GAGguccggg (SEQ ID NO: 1993), GAGguccggu (SEQ ID NO: 1994), GAGguccuug (SEQ ID NO: 1995), GAGgucgggg (SEQ ID NO: 1996), GAGgucucgu (SEQ ID NO: 1997), GAGgucugag (SEQ ID NO: 1998), GAGgucuggu (SEQ ID NO: 1999), GAGgucuguc (SEQ ID NO: 2000), GAGgucuguu (SEQ ID NO: 2001), GAGgucuuuu (SEQ ID NO: 2002), GAGgugaaaa (SEQ ID NO: 2003), GAGgugaaau (SEQ ID NO: 2004), GAGgugaaca (SEQ ID NO: 2005), GAGgugaagg (SEQ ID NO: 2006), GAGgugaaua (SEQ ID NO: 2007), GAGgugaauu (SEQ ID NO: 2008), GAGgugacau (SEQ ID NO: 2009), GAGgugacca (SEQ ID NO: 2010), GAGgugaccu (SEQ ID NO: 2011), GAGgugacua (SEQ ID NO: 2012), GAGgugacuu (SEQ ID NO: 2013), GAGgugagaa (SEQ ID NO: 2014), GAGgugagac (SEQ ID NO: 2015), GAGgugagag (SEQ ID NO: 2016), GAGgugagau (SEQ ID NO: 2017), GAGgugagca (SEQ ID NO: 2018), GAGgugagcc (SEQ ID NO: 2019), GAGgugagcg (SEQ ID NO: 2020), GAGgugagcu (SEQ ID NO: 2021), GAGgugagga (SEQ ID NO: 2022), GAGgugaggc (SEQ ID NO: 2023), GAGgugaggg (SEQ ID NO: 2024), GAGgugagua (SEQ ID NO: 2025), GAGgugagug (SEQ ID NO: 2026), GAGgugaguu (SEQ ID NO: 2027), GAGgugauau (SEQ ID NO: 2028), GAGgugaucc (SEQ ID NO: 2029), GAGgugaucu (SEQ ID NO: 2030), GAGgugauga (SEQ ID NO: 2031), GAGgugaugg (SEQ ID NO: 2032), GAGgugaugu (SEQ ID NO: 2033), GAGgugauuc (SEQ ID NO: 2034), GAGgugcaca (SEQ ID NO: 2035), GAGgugcaga (SEQ ID NO: 2036), GAGgugcagc (SEQ ID NO: 2037), GAGgugcagg (SEQ ID NO: 2038), GAGgugccag (SEQ ID NO: 2039), GAGgugccca (SEQ ID NO: 2040), GAGgugccuu (SEQ ID NO: 2041), GAGgugcggg (SEQ ID NO: 2042), GAGgugcgug (SEQ ID NO: 2043), GAGgugcucc (SEQ ID NO: 2044), GAGgugcugg (SEQ ID NO: 2045), GAGgugcuua (SEQ ID NO: 2046), GAGgugcuug (SEQ ID NO: 2047), GAGguggaaa (SEQ ID NO: 2048), GAGguggaau (SEQ ID NO: 2049), GAGguggacc (SEQ ID NO: 2050), GAGguggacg (SEQ ID NO: 2051), GAGguggagg (SEQ ID NO: 2052), GAGguggcug (SEQ ID NO: 2053), GAGgugggaa (SEQ ID NO: 2054), GAGgugggag (SEQ ID NO: 2055), GAGgugggau (SEQ ID NO: 2056), GAGgugggca (SEQ ID NO: 2057), GAGgugggcg (SEQ ID NO: 2058), GAGgugggcu (SEQ ID NO: 2059), GAGgugggga (SEQ ID NO: 2060), GAGguggggc (SEQ ID NO: 2061), GAGguggggg (SEQ ID NO: 2062), GAGgugggua (SEQ ID NO: 2063), GAGguggguc (SEQ ID NO: 2064), GAGgugggug (SEQ ID NO: 2065), GAGguggguu (SEQ ID NO: 2066), GAGgugguau (SEQ ID NO: 2067), GAGgugguuc (SEQ ID NO: 2068), GAGgugucau (SEQ ID NO: 2069), GAGgugugag (SEQ ID NO: 2070), GAGgugugau (SEQ ID NO: 2071), GAGgugugca (SEQ ID NO: 2072), GAGgugugcu (SEQ ID NO: 2073), GAGgugugga (SEQ ID NO: 2074), GAGguguggg (SEQ ID NO: 2075), GAGguguggu (SEQ ID NO: 2076), GAGgugugua (SEQ ID NO: 2077), GAGgugugug (SEQ ID NO: 2078), GAGguuaaau (SEQ ID NO: 2079), GAGguuaaga (SEQ ID NO: 2080), GAGguuaaua (SEQ ID NO: 2081), GAGguuaccg (SEQ ID NO: 2082), GAGguuagaa (SEQ ID NO: 2083), GAGguuagac (SEQ ID NO: 2084), GAGguuagag (SEQ ID NO: 2085), GAGguuaggu (SEQ ID NO: 2086), GAGguuagua (SEQ ID NO: 2087), GAGguuaguc (SEQ ID NO: 2088), GAGguuagug (SEQ ID NO: 2089), GAGguuaguu (SEQ ID NO: 2090), GAGguuaugu (SEQ ID NO: 2091), GAGguuauuc (SEQ ID NO: 2092), GAGguucaaa (SEQ ID NO: 2093), GAGguucaua (SEQ ID NO: 2094), GAGguucuga (SEQ ID NO: 2095), GAGguugaag (SEQ ID NO: 2096), GAGguugcag (SEQ ID NO: 2097), GAGguugcug (SEQ ID NO: 2098), GAGguuggaa (SEQ ID NO: 2099), GAGguuggag (SEQ ID NO: 2100), GAGguuggau (SEQ ID NO: 2101), GAGguuggua (SEQ ID NO: 2102), GAGguugguc (SEQ ID NO: 2103), GAGguugguu (SEQ ID NO: 2104), GAGguuguag (SEQ ID NO: 2105), GAGguuucug (SEQ ID NO: 2106), GAGguuugag (SEQ ID NO: 2107), GAGguuugga (SEQ ID NO: 2108), GAGguuuggg (SEQ ID NO: 2109), GAGguuugua (SEQ ID NO: 2110), GAGguuuguu (SEQ ID NO: 2111), GAGguuuuca (SEQ ID NO: 2112), GAGguuuuga (SEQ ID NO: 2113), GAGguuuugg (SEQ ID NO: 2114), GAGguuuuua (SEQ ID NO: 2115), GAGguuuuuc (SEQ ID NO: 2116), GAUguaaaau (SEQ ID NO: 2117), GAUguaagca (SEQ ID NO: 2118), GAUguaagcc (SEQ ID NO: 2119), GAUguaaggu (SEQ ID NO: 2120), GAUguaagua (SEQ ID NO: 2121), GAUguaagug (SEQ ID NO: 2122), GAUguaaguu (SEQ ID NO: 2123), GAUguacauc (SEQ ID NO: 2124), GAUguaggua (SEQ ID NO: 2125), GAUguauggc (SEQ ID NO: 2126), GAUguaugua (SEQ ID NO: 2127), GAUguauguu (SEQ ID NO: 2128), GAUgucagug (SEQ ID NO: 2129), GAUgugagag (SEQ ID NO: 2130), GAUgugagcc (SEQ ID NO: 2131), GAUgugagcu (SEQ ID NO: 2132), GAUgugagga (SEQ ID NO: 2133), GAUgugaguc (SEQ ID NO: 2134), GAUgugagug (SEQ ID NO: 2135), GAUgugaguu (SEQ ID NO: 2136), GAUgugggua (SEQ ID NO: 2137), GAUgugggug (SEQ ID NO: 2138), GAUguguguu (SEQ ID NO: 2139), GAUguuagcu (SEQ ID NO: 2140), GAUguucagu (SEQ ID NO: 2141), GAUguucgug (SEQ ID NO: 2142), GAUguuuguu (SEQ ID NO: 2143), GCAguaaagg (SEQ ID NO: 2144), GCAguaagaa (SEQ ID NO: 2145), GCAguaagga (SEQ ID NO: 2146), GCAguaagua (SEQ ID NO: 2147), GCAguaaguc (SEQ ID NO: 2148), GCAguaaguu (SEQ ID NO: 2149), GCAguagaug (SEQ ID NO: 2150), GCAguaggua (SEQ ID NO: 2151), GCAguaugug (SEQ ID NO: 2152), GCAguauguu (SEQ ID NO: 2153), GCAgucagua (SEQ ID NO: 2154), GCAgucagug (SEQ ID NO: 2155), GCAguccggu (SEQ ID NO: 2156), GCAgugacuu (SEQ ID NO: 2157), GCAgugagcc (SEQ ID NO: 2158), GCAgugagcg (SEQ ID NO: 2159), GCAgugagcu (SEQ ID NO: 2160), GCAgugagua (SEQ ID NO: 2161), GCAgugagug (SEQ ID NO: 2162), GCAgugaguu (SEQ ID NO: 2163), GCAgugggua (SEQ ID NO: 2164), GCAguuaagu (SEQ ID NO: 2165), GCAguugagu (SEQ ID NO: 2166), GCCguaaguc (SEQ ID NO: 2167), GCCgugagua (SEQ ID NO: 2168), GCGguaaagc (SEQ ID NO: 2169), GCGguaaaua (SEQ ID NO: 2170), GCGguaagcu (SEQ ID NO: 2171), GCGguaaggg (SEQ ID NO: 2172), GCGguaagug (SEQ ID NO: 2173), GCGguaauca (SEQ ID NO: 2174), GCGguacgua (SEQ ID NO: 2175), GCGguacuug (SEQ ID NO: 2176), GCGguagggu (SEQ ID NO: 2177), GCGguagugu (SEQ ID NO: 2178), GCGgugagca (SEQ ID NO: 2179), GCGgugagcu (SEQ ID NO: 2180), GCGgugaguu (SEQ ID NO: 2181), GCGguggcuc (SEQ ID NO: 2182), GCGgugugca (SEQ ID NO: 2183), GCGguguguu (SEQ ID NO: 2184), GCGguuaagu (SEQ ID NO: 2185), GCGguuugca (SEQ ID NO: 2186), GCUgcuguaa (SEQ ID NO: 2187), GCUguaaaua (SEQ ID NO: 2188), GCUguaagac (SEQ ID NO: 2189), GCUguaagag (SEQ ID NO: 2190), GCUguaagca (SEQ ID NO: 2191), GCUguaagga (SEQ ID NO: 2192), GCUguaagua (SEQ ID NO: 2193), GCUguaaguc (SEQ ID NO: 2194), GCUguaagug (SEQ ID NO: 2195), GCUguaaguu (SEQ ID NO: 2196), GCUguaggug (SEQ ID NO: 2197), GCUguauggu (SEQ ID NO: 2198), GCUgucagug (SEQ ID NO: 2199), GCUguccuug (SEQ ID NO: 2200), GCUgugagaa (SEQ ID NO: 2201), GCUgugagcc (SEQ ID NO: 2202), GCUgugagga (SEQ ID NO: 2203), GCUgugagua (SEQ ID NO: 2204), GCUgugaguc (SEQ ID NO: 2205), GCUgugagug (SEQ ID NO: 2206), GCUgugaguu (SEQ ID NO: 2207), GCUguggguu (SEQ ID NO: 2208), GGAguaagag (SEQ ID NO: 2209), GGAguaagca (SEQ ID NO: 2210), GGAguaagcc (SEQ ID NO: 2211), GGAguaagcu (SEQ ID NO: 2212), GGAguaagga (SEQ ID NO: 2213), GGAguaagug (SEQ ID NO: 2214), GGAguaaguu (SEQ ID NO: 2215), GGAguaauuu (SEQ ID NO: 2216), GGAguacugu (SEQ ID NO: 2217), GGAguaggaa (SEQ ID NO: 2218), GGAguaggua (SEQ ID NO: 2219), GGAguagguu (SEQ ID NO: 2220), GGAguaguau (SEQ ID NO: 2221), GGAguaugac (SEQ ID NO: 2222), GGAguauggu (SEQ ID NO: 2223), GGAgucaagu (SEQ ID NO: 2224), GGAgugaggg (SEQ ID NO: 2225), GGAgugagua (SEQ ID NO: 2226), GGAgugaguc (SEQ ID NO: 2227), GGAgugagug (SEQ ID NO: 2228), GGAgugaguu (SEQ ID NO: 2229), GGAgugcuuu (SEQ ID NO: 2230), GGAgugggca (SEQ ID NO: 2231), GGAgugggug (SEQ ID NO: 2232), GGAguuaagg (SEQ ID NO: 2233), GGAguugaga (SEQ ID NO: 2234), GGCguaagcc (SEQ ID NO: 2235), GGCguaggua (SEQ ID NO: 2236), GGCguaggug (SEQ ID NO: 2237), GGCgugagcc (SEQ ID NO: 2238), GGCgugaguc (SEQ ID NO: 2239), GGGguaaaca (SEQ ID NO: 2240), GGGguaaacc (SEQ ID NO: 2241), GGGguaaacu (SEQ ID NO: 2242), GGGguaagaa (SEQ ID NO: 2243), GGGguaagag (SEQ ID NO: 2244), GGGguaagau (SEQ ID NO: 2245), GGGguaagca (SEQ ID NO: 2246), GGGguaagcc (SEQ ID NO: 2247), GGGguaagcu (SEQ ID NO: 2248), GGGguaagga (SEQ ID NO: 2249), GGGguaaggg (SEQ ID NO: 2250), GGGguaagua (SEQ ID NO: 2251), GGGguaagug (SEQ ID NO: 2252), GGGguaaguu (SEQ ID NO: 2253), GGGguagaca (SEQ ID NO: 2254), GGGguaggag (SEQ ID NO: 2255), GGGguaggcc (SEQ ID NO: 2256), GGGguaggga (SEQ ID NO: 2257), GGGguaggua (SEQ ID NO: 2258), GGGguaggug (SEQ ID NO: 2259), GGGguagguu (SEQ ID NO: 2260), GGGguagugc (SEQ ID NO: 2261), GGGguaucug (SEQ ID NO: 2262), GGGguaugac (SEQ ID NO: 2263), GGGguaugga (SEQ ID NO: 2264), GGGguaugua (SEQ ID NO: 2265), GGGguauguc (SEQ ID NO: 2266), GGGguaugug (SEQ ID NO: 2267), GGGguauguu (SEQ ID NO: 2268), GGGgucagua (SEQ ID NO: 2269), GGGguccgug (SEQ ID NO: 2270), GGGgucggag (SEQ ID NO: 2271), GGGgucugug (SEQ ID NO: 2272), GGGgugaaca (SEQ ID NO: 2273), GGGgugaaga (SEQ ID NO: 2274), GGGgugagaa (SEQ ID NO: 2275), GGGgugagau (SEQ ID NO: 2276), GGGgugagcc (SEQ ID NO: 2277), GGGgugagcg (SEQ ID NO: 2278), GGGgugagcu (SEQ ID NO: 2279), GGGgugagga (SEQ ID NO: 2280), GGGgugaggc (SEQ ID NO: 2281), GGGgugaggg (SEQ ID NO: 2282), GGGgugaguc (SEQ ID NO: 2283), GGGgugagug (SEQ ID NO: 2284), GGGgugaguu (SEQ ID NO: 2285), GGGgugcgua (SEQ ID NO: 2286), GGGguggggu (SEQ ID NO: 2287), GGGgugggua (SEQ ID NO: 2288), GGGgugggug (SEQ ID NO: 2289), GGGguggguu (SEQ ID NO: 2290), GGGgugugcg (SEQ ID NO: 2291), GGGgugugua (SEQ ID NO: 2292), GGGguguguc (SEQ ID NO: 2293), GGGgugugug (SEQ ID NO: 2294), GGGguuacag (SEQ ID NO: 2295), GGGguuggac (SEQ ID NO: 2296), GGGguuggga (SEQ ID NO: 2297), GGGguuugcc (SEQ ID NO: 2298), GGGguuugua (SEQ ID NO: 2299), GGUguaagaa (SEQ ID NO: 2300), GGUguaagau (SEQ ID NO: 2301), GGUguaagca (SEQ ID NO: 2302), GGUguaagcc (SEQ ID NO: 2303), GGUguaagcg (SEQ ID NO: 2304), GGUguaaguc (SEQ ID NO: 2305), GGUguaagug (SEQ ID NO: 2306), GGUguagguc (SEQ ID NO: 2307), GGUguaggug (SEQ ID NO: 2308), GGUguagguu (SEQ ID NO: 2309), GGUguccgua (SEQ ID NO: 2310), GGUgugagag (SEQ ID NO: 2311), GGUgugagcc (SEQ ID NO: 2312), GGUgugagcu (SEQ ID NO: 2313), GGUgugagua (SEQ ID NO: 2314), GGUgugaguc (SEQ ID NO: 2315), GGUgugcuuc (SEQ ID NO: 2316), GGUguggcug (SEQ ID NO: 2317), GGUgugguga (SEQ ID NO: 2318), GGUgugucug (SEQ ID NO: 2319), GGUguugaaa (SEQ ID NO: 2320), GGUguugcug (SEQ ID NO: 2321), GUAguaagau (SEQ ID NO: 2322), GUAguaagua (SEQ ID NO: 2323), GUAguaagug (SEQ ID NO: 2324), GUAguagcuu (SEQ ID NO: 2325), GUAguaggua (SEQ ID NO: 2326), GUAgucagua (SEQ ID NO: 2327), GUAgugagua (SEQ ID NO: 2328), GUAguggugg (SEQ ID NO: 2329), GUAguuaagu (SEQ ID NO: 2330), GUAguuucug (SEQ ID NO: 2331), GUCguaagug (SEQ ID NO: 2332), GUCgugagug (SEQ ID NO: 2333), GUCgugaguu (SEQ ID NO: 2334), GUGgcaagua (SEQ ID NO: 2335), GUGgcuugua (SEQ ID NO: 2336), GUGguaaaau (SEQ ID NO: 2337), GUGguaaaga (SEQ ID NO: 2338), GUGguaaauu (SEQ ID NO: 2339), GUGguaacau (SEQ ID NO: 2340), GUGguaacua (SEQ ID NO: 2341), GUGguaagaa (SEQ ID NO: 2342), GUGguaagac (SEQ ID NO: 2343), GUGguaagag (SEQ ID NO: 2344), GUGguaagau (SEQ ID NO: 2345), GUGguaagca (SEQ ID NO: 2346), GUGguaagcg (SEQ ID NO: 2347), GUGguaagcu (SEQ ID NO: 2348), GUGguaagga (SEQ ID NO: 2349), GUGguaaggc (SEQ ID NO: 2350), GUGguaagua (SEQ ID NO: 2351), GUGguaaguc (SEQ ID NO: 2352), GUGguaagug (SEQ ID NO: 2353), GUGguaaguu (SEQ ID NO: 2354), GUGguaauga (SEQ ID NO: 2355), GUGguaauuc (SEQ ID NO: 2356), GUGguaauuu (SEQ ID NO: 2357), GUGguacaug (SEQ ID NO: 2358), GUGguacgau (SEQ ID NO: 2359), GUGguacuau (SEQ ID NO: 2360), GUGguacuug (SEQ ID NO: 2361), GUGguagaua (SEQ ID NO: 2362), GUGguagcgc (SEQ ID NO: 2363), GUGguaggga (SEQ ID NO: 2364), GUGguagguc (SEQ ID NO: 2365), GUGguaggug (SEQ ID NO: 2366), GUGguagguu (SEQ ID NO: 2367), GUGguauaaa (SEQ ID NO: 2368), GUGguaucuc (SEQ ID NO: 2369), GUGguaugaa (SEQ ID NO: 2370), GUGguaugau (SEQ ID NO: 2371), GUGguaugca (SEQ ID NO: 2372), GUGguaugua (SEQ ID NO: 2373), GUGguauguu (SEQ ID NO: 2374), GUGguccgug (SEQ ID NO: 2375), GUGgucuggc (SEQ ID NO: 2376), GUGgugaaac (SEQ ID NO: 2377), GUGgugagaa (SEQ ID NO: 2378), GUGgugagau (SEQ ID NO: 2379), GUGgugagca (SEQ ID NO: 2380), GUGgugagcu (SEQ ID NO: 2381), GUGgugagga (SEQ ID NO: 2382), GUGgugaggc (SEQ ID NO: 2383), GUGgugagug (SEQ ID NO: 2384), GUGgugaguu (SEQ ID NO: 2385), GUGgugauua (SEQ ID NO: 2386), GUGgugauuc (SEQ ID NO: 2387), GUGgugcgau (SEQ ID NO: 2388), GUGgugcuua (SEQ ID NO: 2389), GUGgugggaa (SEQ ID NO: 2390), GUGgugggua (SEQ ID NO: 2391), GUGguggguc (SEQ ID NO: 2392), GUGguguccg (SEQ ID NO: 2393), GUGguuagca (SEQ ID NO: 2394), GUGguuaggu (SEQ ID NO: 2395), GUGguuagug (SEQ ID NO: 2396), GUGguuugca (SEQ ID NO: 2397), GUGguuugua (SEQ ID NO: 2398), GUUguaaggu (SEQ ID NO: 2399), GUUguaagua (SEQ ID NO: 2400), GUUguaaguc (SEQ ID NO: 2401), GUUguaaguu (SEQ ID NO: 2402), GUUguaccac (SEQ ID NO: 2403), GUUguagcgu (SEQ ID NO: 2404), GUUguaugug (SEQ ID NO: 2405), GUUguauguu (SEQ ID NO: 2406), GUUgucugug (SEQ ID NO: 2407), GUUgugagcu (SEQ ID NO: 2408), GUUgugagug (SEQ ID NO: 2409), GUUgugaguu (SEQ ID NO: 2410), GUUgugggua (SEQ ID NO: 2411), GUUguggguu (SEQ ID NO: 2412), UAAguaaaug (SEQ ID NO: 2413), UAAguaacua (SEQ ID NO: 2414), UAAguaagaa (SEQ ID NO: 2415), UAAguaagag (SEQ ID NO: 2416), UAAguaagau (SEQ ID NO: 2417), UAAguaagca (SEQ ID NO: 2418), UAAguaagcu (SEQ ID NO: 2419), UAAguaagga (SEQ ID NO: 2420), UAAguaaggu (SEQ ID NO: 2421), UAAguaagua (SEQ ID NO: 2422), UAAguaaguc (SEQ ID NO: 2423), UAAguaagug (SEQ ID NO: 2424), UAAguaaguu (SEQ ID NO: 2425), UAAguaauaa (SEQ ID NO: 2426), UAAguacuag (SEQ ID NO: 2427), UAAguaguuu (SEQ ID NO: 2428), UAAguauaaa (SEQ ID NO: 2429), UAAguauaca (SEQ ID NO: 2430), UAAguaugua (SEQ ID NO: 2431), UAAguauuau (SEQ ID NO: 2432), UAAguauuuu (SEQ ID NO: 2433), UAAgucuuuu (SEQ ID NO: 2434), UAAgugagac (SEQ ID NO: 2435), UAAgugagga (SEQ ID NO: 2436), UAAgugaggg (SEQ ID NO: 2437), UAAgugagua (SEQ ID NO: 2438), UAAgugaguc (SEQ ID NO: 2439), UAAgugagug (SEQ ID NO: 2440), UAAgugaguu (SEQ ID NO: 2441), UAAgugaucc (SEQ ID NO: 2442), UAAgugauuc (SEQ ID NO: 2443), UAAgugcgug (SEQ ID NO: 2444), UAAguuaagu (SEQ ID NO: 2445), UAAguuccag (SEQ ID NO: 2446), UAAguucuuu (SEQ ID NO: 2447), UAAguuguaa (SEQ ID NO: 2448), UAAguuguau (SEQ ID NO: 2449), UAAguuuguu (SEQ ID NO: 2450), UACguaacug (SEQ ID NO: 2451), UACguaagaa (SEQ ID NO: 2452), UACguaagau (SEQ ID NO: 2453), UACguaagua (SEQ ID NO: 2454), UACguaagug (SEQ ID NO: 2455), UACguauccu (SEQ ID NO: 2456), UACgucuggc (SEQ ID NO: 2457), UACgugacca (SEQ ID NO: 2458), UAGgcaagac (SEQ ID NO: 2459), UAGgcaaguc (SEQ ID NO: 2460), UAGgcagguc (SEQ ID NO: 2461), UAGgcgugug (SEQ ID NO: 2462), UAGguaaaaa (SEQ ID NO: 2463), UAGguaaaac (SEQ ID NO: 2464), UAGguaaaag (SEQ ID NO: 2465), UAGguaaaau (SEQ ID NO: 2466), UAGguaaaca (SEQ ID NO: 2467), UAGguaaaga (SEQ ID NO: 2468), UAGguaaaua (SEQ ID NO: 2469), UAGguaaauc (SEQ ID NO: 2470), UAGguaaaug (SEQ ID NO: 2471), UAGguaaauu (SEQ ID NO: 2472), UAGguaacac (SEQ ID NO: 2473), UAGguaacag (SEQ ID NO: 2474), UAGguaacau (SEQ ID NO: 2475), UAGguaacca (SEQ ID NO: 2476), UAGguaacgg (SEQ ID NO: 2477), UAGguaacua (SEQ ID NO: 2478), UAGguaacuc (SEQ ID NO: 2479), UAGguaacug (SEQ ID NO: 2480), UAGguaacuu (SEQ ID NO: 2481), UAGguaagac (SEQ ID NO: 2482), UAGguaagag (SEQ ID NO: 2483), UAGguaagau (SEQ ID NO: 2484), UAGguaagca (SEQ ID NO: 2485), UAGguaagcc (SEQ ID NO: 2486), UAGguaagcu (SEQ ID NO: 2487), UAGguaagga (SEQ ID NO: 2488), UAGguaaggc (SEQ ID NO: 2489), UAGguaaggg (SEQ ID NO: 2490), UAGguaagua (SEQ ID NO: 2491), UAGguaaguc (SEQ ID NO: 2492), UAGguaagug (SEQ ID NO: 2493), UAGguaaguu (SEQ ID NO: 2494), UAGguaauag (SEQ ID NO: 2495), UAGguaauau (SEQ ID NO: 2496), UAGguaaucu (SEQ ID NO: 2497), UAGguaauga (SEQ ID NO: 2498), UAGguaaugg (SEQ ID NO: 2499), UAGguaaugu (SEQ ID NO: 2500), UAGguaauua (SEQ ID NO: 2501), UAGguaauuc (SEQ ID NO: 2502), UAGguaauuu (SEQ ID NO: 2503), UAGguacagc (SEQ ID NO: 2504), UAGguacagu (SEQ ID NO: 2505), UAGguacauu (SEQ ID NO: 2506), UAGguaccag (SEQ ID NO: 2507), UAGguaccua (SEQ ID NO: 2508), UAGguaccuu (SEQ ID NO: 2509), UAGguacgag (SEQ ID NO: 2510), UAGguacgua (SEQ ID NO: 2511), UAGguacguu (SEQ ID NO: 2512), UAGguacuau (SEQ ID NO: 2513), UAGguacuga (SEQ ID NO: 2514), UAGguacugg (SEQ ID NO: 2515), UAGguacuuc (SEQ ID NO: 2516), UAGguacuuu (SEQ ID NO: 2517), UAGguagcgg (SEQ ID NO: 2518), UAGguaggaa (SEQ ID NO: 2519), UAGguaggac (SEQ ID NO: 2520), UAGguaggau (SEQ ID NO: 2521), UAGguaggga (SEQ ID NO: 2522), UAGguagggg (SEQ ID NO: 2523), UAGguaggua (SEQ ID NO: 2524), UAGguagguc (SEQ ID NO: 2525), UAGguaggug (SEQ ID NO: 2526), UAGguagguu (SEQ ID NO: 2527), UAGguaguaa (SEQ ID NO: 2528), UAGguagucu (SEQ ID NO: 2529), UAGguagugg (SEQ ID NO: 2530), UAGguagugu (SEQ ID NO: 2531), UAGguaguuu (SEQ ID NO: 2532), UAGguauaaa (SEQ ID NO: 2533), UAGguauaac (SEQ ID NO: 2534), UAGguauaag (SEQ ID NO: 2535), UAGguauaau (SEQ ID NO: 2536), UAGguauaca (SEQ ID NO: 2537), UAGguauacu (SEQ ID NO: 2538), UAGguauaua (SEQ ID NO: 2539), UAGguauauc (SEQ ID NO: 2540), UAGguauauu (SEQ ID NO: 2541), UAGguaucag (SEQ ID NO: 2542), UAGguaucua (SEQ ID NO: 2543), UAGguaucuc (SEQ ID NO: 2544), UAGguaugaa (SEQ ID NO: 2545), UAGguaugag (SEQ ID NO: 2546), UAGguaugca (SEQ ID NO: 2547), UAGguaugga (SEQ ID NO: 2548), UAGguauggc (SEQ ID NO: 2549), UAGguauggu (SEQ ID NO: 2550), UAGguaugua (SEQ ID NO: 2551), UAGguauguc (SEQ ID NO: 2552), UAGguaugug (SEQ ID NO: 2553), UAGguauguu (SEQ ID NO: 2554), UAGguauuaa (SEQ ID NO: 2555), UAGguauuac (SEQ ID NO: 2556), UAGguauuau (SEQ ID NO: 2557), UAGguauuca (SEQ ID NO: 2558), UAGguauucc (SEQ ID NO: 2559), UAGguauucu (SEQ ID NO: 2560), UAGguauuga (SEQ ID NO: 2561), UAGguauuua (SEQ ID NO: 2562), UAGguauuuc (SEQ ID NO: 2563), UAGguauuuu (SEQ ID NO: 2564), UAGgucacuc (SEQ ID NO: 2565), UAGgucagcu (SEQ ID NO: 2566), UAGgucaggu (SEQ ID NO: 2567), UAGgucagua (SEQ ID NO: 2568), UAGgucagug (SEQ ID NO: 2569), UAGgucaguu (SEQ ID NO: 2570), UAGgucaucu (SEQ ID NO: 2571), UAGgucauug (SEQ ID NO: 2572), UAGguccaau (SEQ ID NO: 2573), UAGguccugu (SEQ ID NO: 2574), UAGgucucaa (SEQ ID NO: 2575), UAGgucucgc (SEQ ID NO: 2576), UAGgucuggc (SEQ ID NO: 2577), UAGgucuguc (SEQ ID NO: 2578), UAGgucugug (SEQ ID NO: 2579), UAGgugaagu (SEQ ID NO: 2580), UAGgugaaua (SEQ ID NO: 2581), UAGgugaaug (SEQ ID NO: 2582), UAGgugaauu (SEQ ID NO: 2583), UAGgugacau (SEQ ID NO: 2584), UAGgugacca (SEQ ID NO: 2585), UAGgugacua (SEQ ID NO: 2586), UAGgugagaa (SEQ ID NO: 2587), UAGgugagac (SEQ ID NO: 2588), UAGgugagag (SEQ ID NO: 2589), UAGgugagau (SEQ ID NO: 2590), UAGgugagcc (SEQ ID NO: 2591), UAGgugagcu (SEQ ID NO: 2592), UAGgugagga (SEQ ID NO: 2593), UAGgugaggc (SEQ ID NO: 2594), UAGgugaggu (SEQ ID NO: 2595), UAGgugagua (SEQ ID NO: 2596), UAGgugaguc (SEQ ID NO: 2597), UAGgugagug (SEQ ID NO: 2598), UAGgugauca (SEQ ID NO: 2599), UAGgugauuc (SEQ ID NO: 2600), UAGgugauuu (SEQ ID NO: 2601), UAGgugcaua (SEQ ID NO: 2602), UAGgugcauc (SEQ ID NO: 2603), UAGgugccgu (SEQ ID NO: 2604), UAGgugccug (SEQ ID NO: 2605), UAGgugcgca (SEQ ID NO: 2606), UAGgugcgua (SEQ ID NO: 2607), UAGgugcgug (SEQ ID NO: 2608), UAGgugcuga (SEQ ID NO: 2609), UAGguggaua (SEQ ID NO: 2610), UAGgugggaa (SEQ ID NO: 2611), UAGgugggac (SEQ ID NO: 2612), UAGgugggag (SEQ ID NO: 2613), UAGgugggau (SEQ ID NO: 2614), UAGgugggcc (SEQ ID NO: 2615), UAGgugggcu (SEQ ID NO: 2616), UAGguggguu (SEQ ID NO: 2617), UAGguggugu (SEQ ID NO: 2618), UAGguguaaa (SEQ ID NO: 2619), UAGgugugaa (SEQ ID NO: 2620), UAGgugugag (SEQ ID NO: 2621), UAGgugugca (SEQ ID NO: 2622), UAGgugugcc (SEQ ID NO: 2623), UAGgugugcg (SEQ ID NO: 2624), UAGguguggu (SEQ ID NO: 2625), UAGgugugua (SEQ ID NO: 2626), UAGgugugug (SEQ ID NO: 2627), UAGguguugg (SEQ ID NO: 2628), UAGguuaagc (SEQ ID NO: 2629), UAGguuagac (SEQ ID NO: 2630), UAGguuagcc (SEQ ID NO: 2631), UAGguuaggc (SEQ ID NO: 2632), UAGguuagua (SEQ ID NO: 2633), UAGguuaguc (SEQ ID NO: 2634), UAGguuagug (SEQ ID NO: 2635), UAGguucccc (SEQ ID NO: 2636), UAGguucuac (SEQ ID NO: 2637), UAGguuggua (SEQ ID NO: 2638), UAGguugguu (SEQ ID NO: 2639), UAGguugucc (SEQ ID NO: 2640), UAGguuuauu (SEQ ID NO: 2641), UAGguuugcc (SEQ ID NO: 2642), UAGguuugua (SEQ ID NO: 2643), UAGguuuguc (SEQ ID NO: 2644), UAGguuugug (SEQ ID NO: 2645), UAGguuuguu (SEQ ID NO: 2646), UAGguuuuuc (SEQ ID NO: 2647), UAGguuuuug (SEQ ID NO: 2648), UAUguaagaa (SEQ ID NO: 2649), UAUguaagau (SEQ ID NO: 2650), UAUguaagca (SEQ ID NO: 2651), UAUguaagcc (SEQ ID NO: 2652), UAUguaagua (SEQ ID NO: 2653), UAUguaaguc (SEQ ID NO: 2654), UAUguaagug (SEQ ID NO: 2655), UAUguaaguu (SEQ ID NO: 2656), UAUguacgug (SEQ ID NO: 2657), UAUguacguu (SEQ ID NO: 2658), UAUguagguc (SEQ ID NO: 2659), UAUguagguu (SEQ ID NO: 2660), UAUguauccu (SEQ ID NO: 2661), UAUguaucuc (SEQ ID NO: 2662), UAUguaugua (SEQ ID NO: 2663), UAUguauguc (SEQ ID NO: 2664), UAUguaugug (SEQ ID NO: 2665), UAUguauuau (SEQ ID NO: 2666), UAUgucagaa (SEQ ID NO: 2667), UAUgucugua (SEQ ID NO: 2668), UAUgugaaua (SEQ ID NO: 2669), UAUgugacag (SEQ ID NO: 2670), UAUgugagua (SEQ ID NO: 2671), UAUgugagug (SEQ ID NO: 2672), UAUgugaguu (SEQ ID NO: 2673), UAUgugggca (SEQ ID NO: 2674), UAUgugugua (SEQ ID NO: 2675), UAUguguuua (SEQ ID NO: 2676), UAUguuuugu (SEQ ID NO: 2677), UCAgcgacau (SEQ ID NO: 2678), UCAguaaaau (SEQ ID NO: 2679), UCAguaaaua (SEQ ID NO: 2680), UCAguaacug (SEQ ID NO: 2681), UCAguaagaa (SEQ ID NO: 2682), UCAguaagag (SEQ ID NO: 2683), UCAguaagau (SEQ ID NO: 2684), UCAguaagca (SEQ ID NO: 2685), UCAguaagcc (SEQ ID NO: 2686), UCAguaagcu (SEQ ID NO: 2687), UCAguaaggg (SEQ ID NO: 2688), UCAguaagua (SEQ ID NO: 2689), UCAguaaguc (SEQ ID NO: 2690), UCAguaagug (SEQ ID NO: 2691), UCAguaaguu (SEQ ID NO: 2692), UCAguaucuu (SEQ ID NO: 2693), UCAguaugga (SEQ ID NO: 2694), UCAguauggu (SEQ ID NO: 2695), UCAgucccca (SEQ ID NO: 2696), UCAgugagca (SEQ ID NO: 2697), UCAgugagcu (SEQ ID NO: 2698), UCAgugagua (SEQ ID NO: 2699), UCAgugagug (SEQ ID NO: 2700), UCAgugaguu (SEQ ID NO: 2701), UCAgugauug (SEQ ID NO: 2702), UCAgugggug (SEQ ID NO: 2703), UCAguugagc (SEQ ID NO: 2704), UCAguugauu (SEQ ID NO: 2705), UCAguuuagu (SEQ ID NO: 2706), UCCguaagca (SEQ ID NO: 2707), UCCguaagcu (SEQ ID NO: 2708), UCCguaaguc (SEQ ID NO: 2709), UCCguaagug (SEQ ID NO: 2710), UCCguaauag (SEQ ID NO: 2711), UCCguacuua (SEQ ID NO: 2712), UCCguaugua (SEQ ID NO: 2713), UCCguauguu (SEQ ID NO: 2714), UCCgugagau (SEQ ID NO: 2715), UCCgugaguc (SEQ ID NO: 2716), UCGguaaauu (SEQ ID NO: 2717), UCGguaagag (SEQ ID NO: 2718), UCGguaagcu (SEQ ID NO: 2719), UCGguacauc (SEQ ID NO: 2720), UCGguacucc (SEQ ID NO: 2721), UCGguagacc (SEQ ID NO: 2722), UCGguagguu (SEQ ID NO: 2723), UCGguaguaa (SEQ ID NO: 2724), UCGguaugug (SEQ ID NO: 2725), UCGguauguu (SEQ ID NO: 2726), UCGguauuga (SEQ ID NO: 2727), UCGgucagua (SEQ ID NO: 2728), UCGgucuuag (SEQ ID NO: 2729), UCGgugaagu (SEQ ID NO: 2730), UCGgugagaa (SEQ ID NO: 2731), UCGgugagca (SEQ ID NO: 2732), UCGgugaggc (SEQ ID NO: 2733), UCGgugagua (SEQ ID NO: 2734), UCGgugcgcu (SEQ ID NO: 2735), UCGgugcuuu (SEQ ID NO: 2736), UCGgugguuu (SEQ ID NO: 2737), UCGguuagcu (SEQ ID NO: 2738), UCUguaaaag (SEQ ID NO: 2739), UCUguaagaa (SEQ ID NO: 2740), UCUguaagau (SEQ ID NO: 2741), UCUguaagca (SEQ ID NO: 2742), UCUguaagcu (SEQ ID NO: 2743), UCUguaagua (SEQ ID NO: 2744), UCUguaaguc (SEQ ID NO: 2745), UCUguaagug (SEQ ID NO: 2746), UCUguaaguu (SEQ ID NO: 2747), UCUguaauaa (SEQ ID NO: 2748), UCUguaauga (SEQ ID NO: 2749), UCUguaaugu (SEQ ID NO: 2750), UCUguaggua (SEQ ID NO: 2751), UCUguagguu (SEQ ID NO: 2752), UCUguauaua (SEQ ID NO: 2753), UCUguaugac (SEQ ID NO: 2754), UCUguaugua (SEQ ID NO: 2755), UCUguccucg (SEQ ID NO: 2756), UCUgugagag (SEQ ID NO: 2757), UCUgugagcu (SEQ ID NO: 2758), UCUgugagga (SEQ ID NO: 2759), UCUgugagua (SEQ ID NO: 2760), UCUgugaguc (SEQ ID NO: 2761), UCUgugagug (SEQ ID NO: 2762), UCUgugaguu (SEQ ID NO: 2763), UCUgugcgua (SEQ ID NO: 2764), UCUgugugag (SEQ ID NO: 2765), UGAguaacuu (SEQ ID NO: 2766), UGAguaagau (SEQ ID NO: 2767), UGAguaagca (SEQ ID NO: 2768), UGAguaagcu (SEQ ID NO: 2769), UGAguaaggc (SEQ ID NO: 2770), UGAguaaggu (SEQ ID NO: 2771), UGAguaagua (SEQ ID NO: 2772), UGAguaaguc (SEQ ID NO: 2773), UGAguaagug (SEQ ID NO: 2774), UGAguaaguu (SEQ ID NO: 2775), UGAguaaucc (SEQ ID NO: 2776), UGAguaauua (SEQ ID NO: 2777), UGAguacagu (SEQ ID NO: 2778), UGAguacgua (SEQ ID NO: 2779), UGAguacguu (SEQ ID NO: 2780), UGAguacugu (SEQ ID NO: 2781), UGAguagcug (SEQ ID NO: 2782), UGAguaggua (SEQ ID NO: 2783), UGAguauaaa (SEQ ID NO: 2784), UGAguaugcu (SEQ ID NO: 2785), UGAguaugga (SEQ ID NO: 2786), UGAguaugua (SEQ ID NO: 2787), UGAguauguc (SEQ ID NO: 2788), UGAguauguu (SEQ ID NO: 2789), UGAgucagag (SEQ ID NO: 2790), UGAgucuacg (SEQ ID NO: 2791), UGAgugaaua (SEQ ID NO: 2792), UGAgugaauu (SEQ ID NO: 2793), UGAgugagaa (SEQ ID NO: 2794), UGAgugagau (SEQ ID NO: 2795), UGAgugagca (SEQ ID NO: 2796), UGAgugagcc (SEQ ID NO: 2797), UGAgugagga (SEQ ID NO: 2798), UGAgugagua (SEQ ID NO: 2799), UGAgugagug (SEQ ID NO: 2800), UGAgugaguu (SEQ ID NO: 2801), UGAgugggaa (SEQ ID NO: 2802), UGAguuaaga (SEQ ID NO: 2803), UGAguuaaug (SEQ ID NO: 2804), UGAguuacgg (SEQ ID NO: 2805), UGAguuaggu (SEQ ID NO: 2806), UGAguucuau (SEQ ID NO: 2807), UGAguugguu (SEQ ID NO: 2808), UGAguuguag (SEQ ID NO: 2809), UGAguuuauc (SEQ ID NO: 2810), UGCguaaguc (SEQ ID NO: 2811), UGCguaagug (SEQ ID NO: 2812), UGCguacggc (SEQ ID NO: 2813), UGCguacggg (SEQ ID NO: 2814), UGCguaugua (SEQ ID NO: 2815), UGGgcaaguc (SEQ ID NO: 2816), UGGgcaagug (SEQ ID NO: 2817), UGGgcacauc (SEQ ID NO: 2818), UGGgccacgu (SEQ ID NO: 2819), UGGgccccgg (SEQ ID NO: 2820), UGGguaaaau (SEQ ID NO: 2821), UGGguaaagc (SEQ ID NO: 2822), UGGguaaagg (SEQ ID NO: 2823), UGGguaaagu (SEQ ID NO: 2824), UGGguaaaua (SEQ ID NO: 2825), UGGguaaaug (SEQ ID NO: 2826), UGGguaaauu (SEQ ID NO: 2827), UGGguaacag (SEQ ID NO: 2828), UGGguaacau (SEQ ID NO: 2829), UGGguaacua (SEQ ID NO: 2830), UGGguaacuu (SEQ ID NO: 2831), UGGguaagaa (SEQ ID NO: 2832), UGGguaagac (SEQ ID NO: 2833), UGGguaagag (SEQ ID NO: 2834), UGGguaagau (SEQ ID NO: 2835), UGGguaagca (SEQ ID NO: 2836), UGGguaagcc (SEQ ID NO: 2837), UGGguaagcu (SEQ ID NO: 2838), UGGguaaggg (SEQ ID NO: 2839), UGGguaaggu (SEQ ID NO: 2840), UGGguaagua (SEQ ID NO: 2841), UGGguaaguc (SEQ ID NO: 2842), UGGguaagug (SEQ ID NO: 2843), UGGguaaguu (SEQ ID NO: 2844), UGGguaaugu (SEQ ID NO: 2845), UGGguaauua (SEQ ID NO: 2846), UGGguaauuu (SEQ ID NO: 2847), UGGguacaaa (SEQ ID NO: 2848), UGGguacagu (SEQ ID NO: 2849), UGGguacuac (SEQ ID NO: 2850), UGGguaggga (SEQ ID NO: 2851), UGGguagguc (SEQ ID NO: 2852), UGGguaggug (SEQ ID NO: 2853), UGGguagguu (SEQ ID NO: 2854), UGGguaguua (SEQ ID NO: 2855), UGGguauagu (SEQ ID NO: 2856), UGGguaugaa (SEQ ID NO: 2857), UGGguaugac (SEQ ID NO: 2858), UGGguaugag (SEQ ID NO: 2859), UGGguaugua (SEQ ID NO: 2860), UGGguauguc (SEQ ID NO: 2861), UGGguaugug (SEQ ID NO: 2862), UGGguauguu (SEQ ID NO: 2863), UGGguauuug (SEQ ID NO: 2864), UGGgucuuug (SEQ ID NO: 2865), UGGgugaccu (SEQ ID NO: 2866), UGGgugacua (SEQ ID NO: 2867), UGGgugagac (SEQ ID NO: 2868), UGGgugagag (SEQ ID NO: 2869), UGGgugagca (SEQ ID NO: 2870), UGGgugagcc (SEQ ID NO: 2871), UGGgugagga (SEQ ID NO: 2872), UGGgugaggc (SEQ ID NO: 2873), UGGgugaggg (SEQ ID NO: 2874), UGGgugagua (SEQ ID NO: 2875), UGGgugaguc (SEQ ID NO: 2876), UGGgugagug (SEQ ID NO: 2877), UGGgugaguu (SEQ ID NO: 2878), UGGgugcgug (SEQ ID NO: 2879), UGGguggagg (SEQ ID NO: 2880), UGGguggcuu (SEQ ID NO: 2881), UGGguggggg (SEQ ID NO: 2882), UGGgugggua (SEQ ID NO: 2883), UGGguggguc (SEQ ID NO: 2884), UGGgugggug (SEQ ID NO: 2885), UGGguggguu (SEQ ID NO: 2886), UGGgugugga (SEQ ID NO: 2887), UGGguguguc (SEQ ID NO: 2888), UGGgugugug (SEQ ID NO: 2889), UGGguguguu (SEQ ID NO: 2890), UGGguguuua (SEQ ID NO: 2891), UGGguuaaug (SEQ ID NO: 2892), UGGguuaguc (SEQ ID NO: 2893), UGGguuagug (SEQ ID NO: 2894), UGGguuaguu (SEQ ID NO: 2895), UGGguucaag (SEQ ID NO: 2896), UGGguucgua (SEQ ID NO: 2897), UGGguuggug (SEQ ID NO: 2898), UGGguuuaag (SEQ ID NO: 2899), UGGguuugua (SEQ ID NO: 2900), UGUgcaagua (SEQ ID NO: 2901), UGUguaaaua (SEQ ID NO: 2902), UGUguaagaa (SEQ ID NO: 2903), UGUguaagac (SEQ ID NO: 2904), UGUguaagag (SEQ ID NO: 2905), UGUguaaggu (SEQ ID NO: 2906), UGUguaagua (SEQ ID NO: 2907), UGUguaaguc (SEQ ID NO: 2908), UGUguaaguu (SEQ ID NO: 2909), UGUguacuuc (SEQ ID NO: 2910), UGUguaggcg (SEQ ID NO: 2911), UGUguaggua (SEQ ID NO: 2912), UGUguaguua (SEQ ID NO: 2913), UGUguaugug (SEQ ID NO: 2914), UGUgucagua (SEQ ID NO: 2915), UGUgucugua (SEQ ID NO: 2916), UGUgucuguc (SEQ ID NO: 2917), UGUgugaccc (SEQ ID NO: 2918), UGUgugagau (SEQ ID NO: 2919), UGUgugagca (SEQ ID NO: 2920), UGUgugagcc (SEQ ID NO: 2921), UGUgugagua (SEQ ID NO: 2922), UGUgugaguc (SEQ ID NO: 2923), UGUgugagug (SEQ ID NO: 2924), UGUgugcgug (SEQ ID NO: 2925), UGUgugggug (SEQ ID NO: 2926), UGUguggguu (SEQ ID NO: 2927), UGUgugugag (SEQ ID NO: 2928), UGUguguucu (SEQ ID NO: 2929), UGUguuuaga (SEQ ID NO: 2930), UUAguaaaua (SEQ ID NO: 2931), UUAguaagaa (SEQ ID NO: 2932), UUAguaagua (SEQ ID NO: 2933), UUAguaagug (SEQ ID NO: 2934), UUAguaaguu (SEQ ID NO: 2935), UUAguaggug (SEQ ID NO: 2936), UUAgugagca (SEQ ID NO: 2937), UUAgugaguu (SEQ ID NO: 2938), UUAguuaagu (SEQ ID NO: 2939), UUCguaaguc (SEQ ID NO: 2940), UUCguaaguu (SEQ ID NO: 2941), UUCguaauua (SEQ ID NO: 2942), UUCgugagua (SEQ ID NO: 2943), UUCgugaguu (SEQ ID NO: 2944), UUGgcaagug (SEQ ID NO: 2945), UUGgccgagu (SEQ ID NO: 2946), UUGguaaaaa (SEQ ID NO: 2947), UUGguaaaau (SEQ ID NO: 2948), UUGguaaaga (SEQ ID NO: 2949), UUGguaaagg (SEQ ID NO: 2950), UUGguaaagu (SEQ ID NO: 2951), UUGguaaauc (SEQ ID NO: 2952), UUGguaaaug (SEQ ID NO: 2953), UUGguaaauu (SEQ ID NO: 2954), UUGguaacug (SEQ ID NO: 2955), UUGguaacuu (SEQ ID NO: 2956), UUGguaagaa (SEQ ID NO: 2957), UUGguaagag (SEQ ID NO: 2958), UUGguaagcu (SEQ ID NO: 2959), UUGguaagga (SEQ ID NO: 2960), UUGguaaggg (SEQ ID NO: 2961), UUGguaagua (SEQ ID NO: 2962), UUGguaagug (SEQ ID NO: 2963), UUGguaaguu (SEQ ID NO: 2964), UUGguaauac (SEQ ID NO: 2965), UUGguaauca (SEQ ID NO: 2966), UUGguaaugc (SEQ ID NO: 2967), UUGguaaugu (SEQ ID NO: 2968), UUGguaauug (SEQ ID NO: 2969), UUGguaauuu (SEQ ID NO: 2970), UUGguacaua (SEQ ID NO: 2971), UUGguacgug (SEQ ID NO: 2972), UUGguagagg (SEQ ID NO: 2973), UUGguaggac (SEQ ID NO: 2974), UUGguaggcg (SEQ ID NO: 2975), UUGguaggcu (SEQ ID NO: 2976), UUGguaggga (SEQ ID NO: 2977), UUGguaggua (SEQ ID NO: 2978), UUGguagguc (SEQ ID NO: 2979), UUGguaggug (SEQ ID NO: 2980), UUGguauaaa (SEQ ID NO: 2981), UUGguauaca (SEQ ID NO: 2982), UUGguauauu (SEQ ID NO: 2983), UUGguaucua (SEQ ID NO: 2984), UUGguaucuc (SEQ ID NO: 2985), UUGguaugca (SEQ ID NO: 2986), UUGguaugua (SEQ ID NO: 2987), UUGguaugug (SEQ ID NO: 2988), UUGguauguu (SEQ ID NO: 2989), UUGguauugu (SEQ ID NO: 2990), UUGguauuua (SEQ ID NO: 2991), UUGguauuuu (SEQ ID NO: 2992), UUGgucagaa (SEQ ID NO: 2993), UUGgucagua (SEQ ID NO: 2994), UUGgucucug (SEQ ID NO: 2995), UUGgucugca (SEQ ID NO: 2996), UUGgugaaaa (SEQ ID NO: 2997), UUGgugacug (SEQ ID NO: 2998), UUGgugagac (SEQ ID NO: 2999), UUGgugagau (SEQ ID NO: 3000), UUGgugagca (SEQ ID NO: 3001), UUGgugagga (SEQ ID NO: 3002), UUGgugaggg (SEQ ID NO: 3003), UUGgugagua (SEQ ID NO: 3004), UUGgugaguc (SEQ ID NO: 3005), UUGgugagug (SEQ ID NO: 3006), UUGgugaguu (SEQ ID NO: 3007), UUGgugaugg (SEQ ID NO: 3008), UUGgugauua (SEQ ID NO: 3009), UUGgugauug (SEQ ID NO: 3010), UUGgugcaca (SEQ ID NO: 3011), UUGgugggaa (SEQ ID NO: 3012), UUGguggggc (SEQ ID NO: 3013), UUGgugggua (SEQ ID NO: 3014), UUGguggguc (SEQ ID NO: 3015), UUGgugggug (SEQ ID NO: 3016), UUGguggguu (SEQ ID NO: 3017), UUGguguggu (SEQ ID NO: 3018), UUGguguguc (SEQ ID NO: 3019), UUGgugugug (SEQ ID NO: 3020), UUGguguguu (SEQ ID NO: 3021), UUGguuaagu (SEQ ID NO: 3022), UUGguuagca (SEQ ID NO: 3023), UUGguuagug (SEQ ID NO: 3024), UUGguuaguu (SEQ ID NO: 3025), UUGguuggga (SEQ ID NO: 3026), UUGguugguu (SEQ ID NO: 3027), UUGguuugua (SEQ ID NO: 3028), UUGguuuguc (SEQ ID NO: 3029), UUUgcaagug (SEQ ID NO: 3030), UUUguaaaua (SEQ ID NO: 3031), UUUguaaaug (SEQ ID NO: 3032), UUUguaagaa (SEQ ID NO: 3033), UUUguaagac (SEQ ID NO: 3034), UUUguaagag (SEQ ID NO: 3035), UUUguaagca (SEQ ID NO: 3036), UUUguaaggu (SEQ ID NO: 3037), UUUguaagua (SEQ ID NO: 3038), UUUguaaguc (SEQ ID NO: 3039), UUUguaagug (SEQ ID NO: 3040), UUUguaaguu (SEQ ID NO: 3041), UUUguaauuu (SEQ ID NO: 3042), UUUguacagg (SEQ ID NO: 3043), UUUguacgug (SEQ ID NO: 3044), UUUguacuag (SEQ ID NO: 3045), UUUguacugu (SEQ ID NO: 3046), UUUguagguu (SEQ ID NO: 3047), UUUguauccu (SEQ ID NO: 3048), UUUguauguu (SEQ ID NO: 3049), UUUgugagca (SEQ ID NO: 3050), UUUgugagug (SEQ ID NO: 3051), UUUgugcguc (SEQ ID NO: 3052), UUUguguguc (SEQ ID NO: 3053), and uGGguaccug (SEQ ID NO: 3054). Additional exemplary gene sequences and splice site sequences (e.g., 5’ splice site sequences) include AAGgcaagau (SEQ ID NO: 96), AUGguaugug (SEQ ID NO: 937), GGGgugaggc (SEQ ID NO: 2281), CAGguaggug (SEQ ID NO: 1222), AAGgucagua (SEQ ID NO: 293), AAGguuagag (SEQ ID NO: 3055), AUGgcacuua (SEQ ID NO: 3056), UAAguaaguc (SEQ ID NO: 2423), UGGgugagcu (SEQ ID NO: 3057), CGAgcugggc (SEQ ID NO: 3058), AAAgcacccc (SEQ ID NO: 3059), UAGguggggg (SEQ ID NO: 3060), AGAguaacgu (SEQ ID NO: 3061), UCGgugaugu (SEQ ID NO: 3062), AAUgucaguu (SEQ ID NO: 516), AGGgucugag (SEQ ID NO: 3063), GAGgugacug (SEQ ID NO: 3064), AUGguagguu (SEQ ID NO: 3065), GAGgucuguc (SEQ ID NO: 2000), CAGguaugug (SEQ ID NO: 1260), CAAguacugc (SEQ ID NO: 3066), CACgugcgua (SEQ ID NO: 3067), CCGgugagcu (SEQ ID NO: 3068), CAGguacuuc (SEQ ID NO: 3069), CAGgcgagag (SEQ ID NO: 1115), GAAgcaagua (SEQ ID NO: 3070), AGGgugagca (SEQ ID NO: 789), CAGgcaaguc (SEQ ID NO: 3071), AAGgugaggc (SEQ ID NO: 344), CAGguaagua (SEQ ID NO: 1147), CCAguugggu (SEQ ID NO: 3072), AAGguguggg (SEQ ID NO: 3073), CAGguuggag (SEQ ID NO: 1484), CCGguaugaa (SEQ ID NO: 3074), UGGguaaugu (SEQ ID NO: 2845), CAGgugaggu (SEQ ID NO: 1344), AGAguaauag (SEQ ID NO: 3075), CAGguaugag (SEQ ID NO: 1249), AUGguaaguu (SEQ ID NO: 901), UUGguggguc (SEQ ID NO: 3015), UUUguaagca (SEQ ID NO: 3036), CUCguaugcc (SEQ ID NO: 3076), UAGguaagag (SEQ ID NO: 2483), UAGgcaaguu (SEQ ID NO: 3077), GGAguuaagu (SEQ ID NO: 3078), GAGguaugcc (SEQ ID NO: 1959), AAGguguggu (SEQ ID NO: 402), CAGgugggug (SEQ ID NO: 1415), UUAguaagua (SEQ ID NO: 2933), AAGguuggcu (SEQ ID NO: 3079), UGAguaugug (SEQ ID NO: 3080), CCAgccuucc (SEQ ID NO: 3081), CCUguacgug (SEQ ID NO: 3082), CCUguaggua (SEQ ID NO: 1601), CAGguacgcu (SEQ ID NO: 3083), GAGguucuuc (SEQ ID NO: 3084), AAGguugccu (SEQ ID NO: 3085), CGUguucacu (SEQ ID NO: 3086), CGGgugggga (SEQ ID NO: 3087), UAGgugggau (SEQ ID NO: 2614), CGGguaagga (SEQ ID NO: 3088), AAGguacuau (SEQ ID NO: 195), GGGguaagcu (SEQ ID NO: 2248), ACGguagagc (SEQ ID NO: 3089), CAGgugaaga (SEQ ID NO: 1318), GCGguaagag (SEQ ID NO: 3090), CAGguguugu (SEQ ID NO: 3091), GAAguuugug (SEQ ID NO: 3092), AUGgugagca (SEQ ID NO: 955), CGGguucgug (SEQ ID NO: 3093), AUUguccggc (SEQ ID NO: 3094), GAUgugugug (SEQ ID NO: 3095), AUGgucuguu (SEQ ID NO: 3096), AAGguaggau (SEQ ID NO: 219), CCGguaagau (SEQ ID NO: 1575), AAGguaaaga (SEQ ID NO: 126), GGGgugaguu (SEQ ID NO: 2285), AGGguuggug (SEQ ID NO: 808), GGAgugagug (SEQ ID NO: 2228), AGUguaagga (SEQ ID NO: 3097), UAGguaacug (SEQ ID NO: 2480), AAGgugaaga (SEQ ID NO: 3098), UGGguaagug (SEQ ID NO: 2843), CAGguaagag (SEQ ID NO: 1140), UAGgugagcg (SEQ ID NO: 3099), GAGguaaaaa (SEQ ID NO: 1865), GCCguaaguu (SEQ ID NO: 3100), AAGguuuugu (SEQ ID NO: 473), CAGgugagga (SEQ ID NO: 1341), ACAgcccaug (SEQ ID NO: 3101), GCGgugagcc (SEQ ID NO: 3102), CAGguaugca (SEQ ID NO: 1251), AUGguaccua (SEQ ID NO: 3103), CAAguaugua (SEQ ID NO: 1050), AUGguggugc (SEQ ID NO: 3104), UAAguggcag (SEQ ID NO: 3105), UAGguauagu (SEQ ID NO: 3106), CUGguauuua (SEQ ID NO: 3107), AGGguaaacg (SEQ ID NO: 3108), AUAguaagug (SEQ ID NO: 850), UUGguacuga (SEQ ID NO: 3109), GGUguaagcc (SEQ ID NO: 2303), GAGguggaua (SEQ ID NO: 3110), GAUguaagaa (SEQ ID NO: 3111), ACGgucaguu (SEQ ID NO: 3112), UAAguaaaca (SEQ ID NO: 3113), AAGguaucug (SEQ ID NO: 251), AGGguauuug (SEQ ID NO: 3114), AAGgugaaug (SEQ ID NO: 328), CUGgugaauu (SEQ ID NO: 1749), CAGguuuuuu (SEQ ID NO: 1514), CAUguaugug (SEQ ID NO: 1534), UUGguagagg (SEQ ID NO: 2973), AAGguaugcc (SEQ ID NO: 258), CAGgugccac (SEQ ID NO: 3115), UCGguauuga (SEQ ID NO: 2727), AAGguuugug (SEQ ID NO: 468), AAUguacagg (SEQ ID NO: 3116), CAUguggguu (SEQ ID NO: 1545), CAUgugaguu (SEQ ID NO: 1542), UUGguaaugu (SEQ ID NO: 2968), AGUguaggug (SEQ ID NO: 3117), GAGguaacuc (SEQ ID NO: 3118), GAGguggcgc (SEQ ID NO: 3119), CUGguaauug (SEQ ID NO: 3120), GAGguuugcu (SEQ ID NO: 3121), UGUguacgug (SEQ ID NO: 3122), UAGguaaaga (SEQ ID NO: 2468), CUAguaggca (SEQ ID NO: 3123), UCUgugaguc (SEQ ID NO: 2761), UCUguaaggc (SEQ ID NO: 3124), CAGguuugug (SEQ ID NO: 1509), GAGguagggc (SEQ ID NO: 1935), AAGguaacca (SEQ ID NO: 3125), ACUgugaguu (SEQ ID NO: 646), UAGguaauag (SEQ ID NO: 2495), AAAguaagcu (SEQ ID NO: 17), AUGgugagug (SEQ ID NO: 963), UAGguuugug (SEQ ID NO: 2645), AACguaggac (SEQ ID NO: 3126), GUAgcaggua (SEQ ID NO: 3127), GAGgucagac (SEQ ID NO: 3128), AGGguaugaa (SEQ ID NO: 3129), GAGguuagug (SEQ ID NO: 2089), CAGgcacgug (SEQ ID NO: 3130), GGGgcaagac (SEQ ID NO: 3131), CAGguguguc (SEQ ID NO: 1441), CAGguauuga (SEQ ID NO: 1265), CAGguauguc (SEQ ID NO: 1259), AAGgcaaggu (SEQ ID NO: 3132), UUGgugagaa (SEQ ID NO: 3133), AAGguaaaau (SEQ ID NO: 122), GGGguaagua (SEQ ID NO: 2251), AAGguaucuu (SEQ ID NO: 252), GACgugaguc (SEQ ID NO: 3134), UAUguaugcu (SEQ ID NO: 3135), AAGguacugu (SEQ ID NO: 199), CAGgugaacu (SEQ ID NO: 3136), CACguaaaug (SEQ ID NO: 3137), AAGgugugau (SEQ ID NO: 3138), GAAguauuug (SEQ ID NO: 3139), AAGgucugug (SEQ ID NO: 3140), AAGguggagg (SEQ ID NO: 3141), AAGguauaug (SEQ ID NO: 244), CAGguucuua (SEQ ID NO: 1477), AGGguaacca (SEQ ID NO: 730), CAGgugucac (SEQ ID NO: 1423), AAAguucugu (SEQ ID NO: 3142), UUGgugaguu (SEQ ID NO: 3007), CAAgugaguc (SEQ ID NO: 1067), UAGguagguc (SEQ ID NO: 2525), GCGgugagcu (SEQ ID NO: 2180), AUUgugagga (SEQ ID NO: 3143), CAGgugcaca (SEQ ID NO: 1361), CAGguuggaa (SEQ ID NO: 3144), CUGgucacuu (SEQ ID NO: 3145), GGAguaagug (SEQ ID NO: 2214), GAGgugggcu (SEQ ID NO: 2059), AAGguacuug (SEQ ID NO: 201), AGGguaggau (SEQ ID NO: 3146), AAUguguguu (SEQ ID NO: 3147), ACAguuaagu (SEQ ID NO: 568), GAGgugugug (SEQ ID NO: 2078), AAGgcgggcu (SEQ ID NO: 3148), AUAgcaagua (SEQ ID NO: 3149), AAGguuguua (SEQ ID NO: 454), CAAgcaaggc (SEQ ID NO: 3150), GUGguaauua (SEQ ID NO: 3151), UCUguucagu (SEQ ID NO: 3152), AGGguaggcc (SEQ ID NO: 754), AAGguaucau (SEQ ID NO: 3153), UAGguaccuu (SEQ ID NO: 2509), AAGguaugac (SEQ ID NO: 254), GGAguaggua (SEQ ID NO: 2219), UAAguuggca (SEQ ID NO: 3154), AGUgugaggc (SEQ ID NO: 3155), GAGguuugug (SEQ ID NO: 3156), UGGgucugcu (SEQ ID NO: 3157), CAGgugaucc (SEQ ID NO: 1350), CAGgucagug (SEQ ID NO: 1283), AAGguaaggg (SEQ ID NO: 151), CAGgugcagu (SEQ ID NO: 3158), GAGguggguc (SEQ ID NO: 2064), GCUgugagug (SEQ ID NO: 2206), AAGguggagu (SEQ ID NO: 3159), GGGgucaguu (SEQ ID NO: 3160), AGCguaagug (SEQ ID NO: 719), AGAguaugaa (SEQ ID NO: 691), GGGguagggu (SEQ ID NO: 3161), AAGgccagca (SEQ ID NO: 3162), CGAguaugcc (SEQ ID NO: 3163), GUGgugagcg (SEQ ID NO: 3164), AAUguaaauu (SEQ ID NO: 481), CAGgugcgca (SEQ ID NO: 1375), GGUguaugaa (SEQ ID NO: 3165), CUUgugaguu (SEQ ID NO: 1804), AAGguaucuc (SEQ ID NO: 250), AGAguaagga (SEQ ID NO: 665), UAGguaagac (SEQ ID NO: 2482), GAGgugagug (SEQ ID NO: 2026), CAGguguguu (SEQ ID NO: 1443), UUGgugagua (SEQ ID NO: 3004), AGGgcgaguu (SEQ ID NO: 3166), CAGguuuugc (SEQ ID NO: 3167), UUUgugaguu (SEQ ID NO: 3168), AGGguaagca (SEQ ID NO: 736), GAGguccucu (SEQ ID NO: 3169), CCAgcaggua (SEQ ID NO: 3170), GAGguucgcg (SEQ ID NO: 3171), CAGgugaucu (SEQ ID NO: 1351), ACUguaagua (SEQ ID NO: 625), AAGguaaauc (SEQ ID NO: 131), CAGgcaaaua (SEQ ID NO: 3172), GUGguaagca (SEQ ID NO: 2346), CAGguuaaau (SEQ ID NO: 3173), UUGguaauaa (SEQ ID NO: 3174), UAUguaggua (SEQ ID NO: 3175), CAGguaguau (SEQ ID NO: 1225), AAGgugugcc (SEQ ID NO: 3176), UGGguaagag (SEQ ID NO: 2834), CAGgcaagca (SEQ ID NO: 3177), UUGguaaggg (SEQ ID NO: 2961), AAGgcaggug (SEQ ID NO: 109), ACGguaaaug (SEQ ID NO: 3178), GCUgugagca (SEQ ID NO: 3179), AUGguacaca (SEQ ID NO: 3180), GUAguguguu (SEQ ID NO: 3181), ACUguaagag (SEQ ID NO: 3182), CCCgcagguc (SEQ ID NO: 3183), GAGgugagcc (SEQ ID NO: 2019), GAGgugcugu (SEQ ID NO: 3184), UAAguaugcu (SEQ ID NO: 3185), GAGgccaucu (SEQ ID NO: 3186), UCAgugagug (SEQ ID NO: 2700), CAGgugcuac (SEQ ID NO: 3187), AAUgugggug (SEQ ID NO: 533), GAGgugugaa (SEQ ID NO: 3188), CUGguagguc (SEQ ID NO: 1730), GUGgcgcgcg (SEQ ID NO: 3189), CAGgugcaaa (SEQ ID NO: 1359), UAAguggagg (SEQ ID NO: 3190), CAUgugggua (SEQ ID NO: 3191), GAGguagggu (SEQ ID NO: 3192), AAAgugaguu (SEQ ID NO: 61), AGGguucuag (SEQ ID NO: 3193), UGUgugagcu (SEQ ID NO: 3194), AGGgugaauc (SEQ ID NO: 3195), CAGgucaggg (SEQ ID NO: 3196), AAGgucccug (SEQ ID NO: 3197), CUGguagagu (SEQ ID NO: 3198), UAGgucaguu (SEQ ID NO: 2570), AAAguaaggg (SEQ ID NO: 19), CAAguaugug (SEQ ID NO: 1052), CAGgugcuuu (SEQ ID NO: 3199), AAGguaauuc (SEQ ID NO: 169), GGGgugcacg (SEQ ID NO: 3200), ACUgugcuac (SEQ ID NO: 3201), CAGguaccua (SEQ ID NO: 3202), CAGguagcuu (SEQ ID NO: 1211), UGGgugaggc (SEQ ID NO: 2873), CUGguacauu (SEQ ID NO: 1718), AGGguaaucu (SEQ ID NO: 3203), CAGguacaag (SEQ ID NO: 1161), CAGguaauuc (SEQ ID NO: 1157), AGGgcacuug (SEQ ID NO: 3204), UAGgugagaa (SEQ ID NO: 2587), GAGguaaugc (SEQ ID NO: 3205), CCAgugaguu (SEQ ID NO: 3206), AAAguaugug (SEQ ID NO: 44), CUGgugaauc (SEQ ID NO: 3207), UAUguaugua (SEQ ID NO: 2663), CCUgcaggug (SEQ ID NO: 3208), CAGguaucug (SEQ ID NO: 1245), GAGgugaggu (SEQ ID NO: 3209), CUGguaaaac (SEQ ID NO: 3210), UGUgugugcu (SEQ ID NO: 3211), CAGguuaagu (SEQ ID NO: 3212), CAGguaaucc (SEQ ID NO: 1152), UAGguauuug (SEQ ID NO: 3213), UGGguagguc (SEQ ID NO: 2852), CAGguaacag (SEQ ID NO: 1129), AGCgugcgug (SEQ ID NO: 3214), AAGgucagga (SEQ ID NO: 289), GGUgugagcc (SEQ ID NO: 2312), CUGguaagua (SEQ ID NO: 1707), GGGgugggca (SEQ ID NO: 3215), AAGgugggaa (SEQ ID NO: 376), CAGgugagug (SEQ ID NO: 1347), CUGguuguua (SEQ ID NO: 3216), CAGguaauag (SEQ ID NO: 3217), UAGgugaguu (SEQ ID NO: 3218), AGAguaaguu (SEQ ID NO: 671), UAGguaaucc (SEQ ID NO: 3219), CCGgugacug (SEQ ID NO: 3220), GUCgugauua (SEQ ID NO: 3221), CUUguaagug (SEQ ID NO: 1794), UAGguaguca (SEQ ID NO: 3222), CUGguaaguc (SEQ ID NO: 3223), AGGgugagcg (SEQ ID NO: 3224), CAGguaugga (SEQ ID NO: 1255), AUUgugacca (SEQ ID NO: 3225), GUUgugggua (SEQ ID NO: 2411), AAGguacaag (SEQ ID NO: 173), CUAgcaagug (SEQ ID NO: 3226), CUGgugagau (SEQ ID NO: 3227), CAGgugggca (SEQ ID NO: 1406), AUGgcucgag (SEQ ID NO: 3228), CUGguacguu (SEQ ID NO: 1720), UUGgugugua (SEQ ID NO: 3229), GAGgugucug (SEQ ID NO: 3230), GAGgugggac (SEQ ID NO: 3231), GGGgugggag (SEQ ID NO: 3232), GCAgcgugag (SEQ ID NO: 3233), GAGguaaaga (SEQ ID NO: 1870), GAGguaugua (SEQ ID NO: 1965), AAGgugagac (SEQ ID NO: 336), AAGguacaau (SEQ ID NO: 174), CUGguaugag (SEQ ID NO: 3234), AACguaaaau (SEQ ID NO: 3235), GUGguaggga (SEQ ID NO: 2364), CUGguaugug (SEQ ID NO: 1737), CUUguaagca (SEQ ID NO: 3236), AAGguaggga (SEQ ID NO: 223), AUUguaagcc (SEQ ID NO: 3237), AUGguaagcu (SEQ ID NO: 895), CAGgugaauu (SEQ ID NO: 1322), UAGgugaaua (SEQ ID NO: 2581), CAAguaugga (SEQ ID NO: 3238), AUGguauggc (SEQ ID NO: 936), GAGgucaugc (SEQ ID NO: 3239), CAGguacccu (SEQ ID NO: 1174), ACAgugagac (SEQ ID NO: 3240), CAGgucugau (SEQ ID NO: 3241), GAAguugggu (SEQ ID NO: 3242), CUGgugcgug (SEQ ID NO: 1767), CAGguacgag (SEQ ID NO: 1180), ACAgugagcc (SEQ ID NO: 556), AAGguaagua (SEQ ID NO: 153), GGAguaaggc (SEQ ID NO: 3243), GAGgugugua (SEQ ID NO: 2077), AAGgucauuu (SEQ ID NO: 3244), CAGguagucu (SEQ ID NO: 3245), AUGguaucug (SEQ ID NO: 3246), AAGguaaacu (SEQ ID NO: 125), GAGguaggug (SEQ ID NO: 1938), CUGguaagca (SEQ ID NO: 1700), AGGguaagag (SEQ ID NO: 734), AAAguaaagc (SEQ ID NO: 3247), CAGguuugag (SEQ ID NO: 1502), GAGgcgggua (SEQ ID NO: 3248), CGAguacgau (SEQ ID NO: 3249), CAGguuguug (SEQ ID NO: 1495), AAAguauggg (SEQ ID NO: 3250), UAGgcugguc (SEQ ID NO: 3251), AAGguaagga (SEQ ID NO: 149), AAGguuuccu (SEQ ID NO: 458), UUGguaaaac (SEQ ID NO: 3252), GAGguaagua (SEQ ID NO: 1893), CAGguucaag (SEQ ID NO: 1465), UGGguuaugu (SEQ ID NO: 3253), GAGgugaguu (SEQ ID NO: 2027), ACGgugaaac (SEQ ID NO: 598), GAUguaacca (SEQ ID NO: 3254), AAGgugcggg (SEQ ID NO: 3255), CCGguacgug (SEQ ID NO: 3256), GAUgugagaa (SEQ ID NO: 3257), GUGgcgguga (SEQ ID NO: 3258), CAGguauuag (SEQ ID NO: 3259), GAGguuggga (SEQ ID NO: 3260), AAGgcuagua (SEQ ID NO: 3261), AAGgugggcg (SEQ ID NO: 381), CAGgcaggga (SEQ ID NO: 3262), AAUguuaguu (SEQ ID NO: 3263), GAGguaaagg (SEQ ID NO: 3264), CAGgugugcu (SEQ ID NO: 1437), CUGguaugau (SEQ ID NO: 1733), AUGguuaguc (SEQ ID NO: 978), CUGgugagaa (SEQ ID NO: 1751), CAGgccggcg (SEQ ID NO: 3265), CAGgugacug (SEQ ID NO: 1332), AAAguaaggu (SEQ ID NO: 20), UAAguacuug (SEQ ID NO: 3266), AAGguaaagc (SEQ ID NO: 127), UCGguagggg (SEQ ID NO: 3267), CAGguaggaa (SEQ ID NO: 1212), AGUguaagca (SEQ ID NO: 817), CCCgugagau (SEQ ID NO: 3268), GUGguuguuu (SEQ ID NO: 3269), CAGguuugcc (SEQ ID NO: 1504), AGGguauggg (SEQ ID NO: 766), UAAguaagug (SEQ ID NO: 2424), GAGguaagac (SEQ ID NO: 3270), GAUguagguc (SEQ ID NO: 3271), CAAguaggug (SEQ ID NO: 1043), AUAguaaaua (SEQ ID NO: 845), GAGguugggg (SEQ ID NO: 3272), GAGgcgagua (SEQ ID NO: 3273), CAGguagugu (SEQ ID NO: 1229), GUGguaggug (SEQ ID NO: 2366), CAAgugagug (SEQ ID NO: 1068), AAGgugacaa (SEQ ID NO: 330), CCAgcguaau (SEQ ID NO: 3274), ACGgugaggu (SEQ ID NO: 3275), GGGguauauu (SEQ ID NO: 3276), CAGgugagua (SEQ ID NO: 1345), AAGgugcgug (SEQ ID NO: 364), UAUguaaauu (SEQ ID NO: 3277), CAGgucagua (SEQ ID NO: 1281), ACGguacuua (SEQ ID NO: 3278), GAGgucagca (SEQ ID NO: 3279), UAAguaugua (SEQ ID NO: 2431), GGGgucagac (SEQ ID NO: 3280), AAUgugugag (SEQ ID NO: 3281), UCCgucagua (SEQ ID NO: 3282), CAGgugcuuc (SEQ ID NO: 1391), CCAguuagug (SEQ ID NO: 3283), CCGgugggcg (SEQ ID NO: 1590), AGGgugcaug (SEQ ID NO: 3284), GGGguaggau (SEQ ID NO: 3285), UAGgugggcc (SEQ ID NO: 2615), GAGguguucg (SEQ ID NO: 3286), UUGgcaagaa (SEQ ID NO: 3287), UCCguaagua (SEQ ID NO: 3288), CAGguguaag (SEQ ID NO: 3289), CUCgugagua (SEQ ID NO: 1680), GAGguguuuu (SEQ ID NO: 3290), GAGgugagca (SEQ ID NO: 2018), GAGguaaagu (SEQ ID NO: 1872), AAGguacguu (SEQ ID NO: 193), CAGguccagu (SEQ ID NO: 1291), AUGgugaaac (SEQ ID NO: 947), GUAgugagcu (SEQ ID NO: 3291), CAGgugaaaa (SEQ ID NO: 3292), AGGguacagg (SEQ ID NO: 3293), AAGguaacgc (SEQ ID NO: 3294), AAGguauacc (SEQ ID NO: 3295), CCUgugagau (SEQ ID NO: 3296), GGGguacgug (SEQ ID NO: 3297), GAGguauggu (SEQ ID NO: 1964), UAGguauuau (SEQ ID NO: 2557), GAAguaggag (SEQ ID NO: 3298), UCGguaaggg (SEQ ID NO: 3299), CCGguaagcg (SEQ ID NO: 3300), GAAguaauua (SEQ ID NO: 1823), CAGgugaguc (SEQ ID NO: 1346), AAGgucaaga (SEQ ID NO: 279), AUGguaaguc (SEQ ID NO: 899), CAGgugagcu (SEQ ID NO: 1340), CCAguuuuug (SEQ ID NO: 3301), CAGgugggag (SEQ ID NO: 1404), AAGguauuau (SEQ ID NO: 270), AAGguaaaua (SEQ ID NO: 130), AAGgugcugu (SEQ ID NO: 3302), AAAguacacc (SEQ ID NO: 3303), CUGguucgug (SEQ ID NO: 1783), UCAguaaguc (SEQ ID NO: 2690), GAAguacgug (SEQ ID NO: 3304), CAGgugacaa (SEQ ID NO: 1323), UGGguaagaa (SEQ ID NO: 2832), UGUguagggg (SEQ ID NO: 3305), GAGguaggca (SEQ ID NO: 1932), UUGgugaggc (SEQ ID NO: 3306), AUGgugugua (SEQ ID NO: 974), CAGguccucc (SEQ ID NO: 3307), UUGguaaaug (SEQ ID NO: 2953), GCUgugaguu (SEQ ID NO: 2207), AUGgucugua (SEQ ID NO: 3308), CAUgcaggug (SEQ ID NO: 3309), CUGguacacc (SEQ ID NO: 3310), CAGguccuua (SEQ ID NO: 3311), CAAguaaucu (SEQ ID NO: 1031), AUGgcagccu (SEQ ID NO: 3312), AAGgucagaa (SEQ ID NO: 282), AACgugaggc (SEQ ID NO: 3313), CAGgcacgca (SEQ ID NO: 1106), ACGguccagg (SEQ ID NO: 3314), UCUguacaua (SEQ ID NO: 3315), GAGgugauua (SEQ ID NO: 3316), ACGguaaaua (SEQ ID NO: 3317), AUGguaacug (SEQ ID NO: 3318), CAGgcgcguu (SEQ ID NO: 3319), CAGguauaga (SEQ ID NO: 1235), AAGguuuguu (SEQ ID NO: 3320), CAGguaugaa (SEQ ID NO: 1247), UAGguuggua (SEQ ID NO: 2638), CUGgugagac (SEQ ID NO: 1752), CAGguuagga (SEQ ID NO: 3321), AUGgugacug (SEQ ID NO: 3322), UUGguauccc (SEQ ID NO: 3323), CUUguaggac (SEQ ID NO: 3324), AAAguguguu (SEQ ID NO: 69), CAGguuucuu (SEQ ID NO: 1500), GGGguauggc (SEQ ID NO: 3325), GGGguaggac (SEQ ID NO: 3326), ACUguaaguc (SEQ ID NO: 626), AUCguaagcu (SEQ ID NO: 3327), UAGguucccc (SEQ ID NO: 2636), GGUgugagca (SEQ ID NO: 3328), CUGguuggua (SEQ ID NO: 3329), GGGguuaggg (SEQ ID NO: 3330), UGAguaagaa (SEQ ID NO: 3331), GAGguauucc (SEQ ID NO: 1969), UGGguuaguc (SEQ ID NO: 2893), CAGgcucgug (SEQ ID NO: 3332), UAGguagagu (SEQ ID NO: 3333), UAGgugcccu (SEQ ID NO: 3334), AAAgugagua (SEQ ID NO: 58), GAGguucaua (SEQ ID NO: 2094), UUGguaagag (SEQ ID NO: 2958), ACCgugugua (SEQ ID NO: 3335), UAUguaguau (SEQ ID NO: 3336), UGGguaauag (SEQ ID NO: 3337), CAGgucugaa (SEQ ID NO: 3338), AAAguauaaa (SEQ ID NO: 3339), GUGgugaguc (SEQ ID NO: 3340), AGUgugauua (SEQ ID NO: 3341), UUGgugugug (SEQ ID NO: 3020), CAGgugaugg (SEQ ID NO: 1353), GCUgugagua (SEQ ID NO: 2204), CAGguacaug (SEQ ID NO: 1169), AAGguacagu (SEQ ID NO: 178), GAAguuguag (SEQ ID NO: 3342), CAGgugauua (SEQ ID NO: 1355), UAGgugaauu (SEQ ID NO: 2583), GGUguuaaua (SEQ ID NO: 3343), CAGguauuua (SEQ ID NO: 1268), CAAguacucg (SEQ ID NO: 3344), CAAguaagaa (SEQ ID NO: 1022), AAGguaccuu (SEQ ID NO: 188), ACGgugaggg (SEQ ID NO: 3345), UGAgcaggca (SEQ ID NO: 3346), GGGgugaccg (SEQ ID NO: 3347), GAGguaaaug (SEQ ID NO: 1875), CGGguuugug (SEQ ID NO: 3348), AAGgugagcg (SEQ ID NO: 341), GUGguaugga (SEQ ID NO: 3349), CUGguaagga (SEQ ID NO: 1703), GAGguaccag (SEQ ID NO: 1911), CCGgugagug (SEQ ID NO: 1587), AAGguuagaa (SEQ ID NO: 416), GAGguacuug (SEQ ID NO: 1921), AGAguaaaac (SEQ ID NO: 651), UCUgugagua (SEQ ID NO: 2760), AAGgcgggaa (SEQ ID NO: 3350), CAGguaugcg (SEQ ID NO: 1253), AGGguaaaac (SEQ ID NO: 3351), AAGgugacug (SEQ ID NO: 333), AGGguauguu (SEQ ID NO: 3352), AAGguaugua (SEQ ID NO: 263), CAGgucucuc (SEQ ID NO: 1302), CAGgcaugua (SEQ ID NO: 3353), CUGguaggua (SEQ ID NO: 1729), AAGgucaugc (SEQ ID NO: 3354), CAGguacaca (SEQ ID NO: 1163), GAUguacguu (SEQ ID NO: 3355), ACAguacgug (SEQ ID NO: 3356), ACGguaccca (SEQ ID NO: 3357), CAGguagugc (SEQ ID NO: 3358), ACAguaagag (SEQ ID NO: 3359), GGUgcacacc (SEQ ID NO: 3360), GAGguguaac (SEQ ID NO: 3361), AAGgugugua (SEQ ID NO: 403), UAGguacuua (SEQ ID NO: 3362), GCGguacugc (SEQ ID NO: 3363), UGGguaaguc (SEQ ID NO: 2842), CAUguaggua (SEQ ID NO: 1529), CAGguaggau (SEQ ID NO: 3364), CAGgucuggc (SEQ ID NO: 3365), GUGguuuuaa (SEQ ID NO: 3366), CAGgugggaa (SEQ ID NO: 1402), UGGgugagua (SEQ ID NO: 2875), CGAgugagcc (SEQ ID NO: 3367), AAGguauggc (SEQ ID NO: 261), AGUguuguca (SEQ ID NO: 3368), CAGgugauuu (SEQ ID NO: 1358), UAGguaucuc (SEQ ID NO: 2544), UAAguauguu (SEQ ID NO: 3369), AAGguugagc (SEQ ID NO: 3370), AGAguaaaga (SEQ ID NO: 653), GGUguaagua (SEQ ID NO: 3371), GGGgugagcu (SEQ ID NO: 2279), CAGguauaau (SEQ ID NO: 3372), GAGguacaaa (SEQ ID NO: 1904), AUGguaccaa (SEQ ID NO: 3373), UAGguagggg (SEQ ID NO: 2523), UGAgucagaa (SEQ ID NO: 3374), AAGgcaauua (SEQ ID NO: 3375), UUGguaagau (SEQ ID NO: 3376), CAGguacaga (SEQ ID NO: 1165), AGAguuagag (SEQ ID NO: 3377), CAGgugcguc (SEQ ID NO: 1381), GAGguauuac (SEQ ID NO: 3378), ACGguacaga (SEQ ID NO: 3379), CAGgucuucc (SEQ ID NO: 1313), AAGguaaggu (SEQ ID NO: 152), GAGguaauuu (SEQ ID NO: 1903), AGUguaggcu (SEQ ID NO: 3380), AAAguaagcg (SEQ ID NO: 3381), CCUguaagcc (SEQ ID NO: 3382), AGGgugauuu (SEQ ID NO: 3383), UGUguaugaa (SEQ ID NO: 3384), CUGguacaca (SEQ ID NO: 3385), AGGguagaga (SEQ ID NO: 3386), AUAguaagca (SEQ ID NO: 848), AGAguaugua (SEQ ID NO: 3387), UUGgucagca (SEQ ID NO: 3388), CAGgcaaguu (SEQ ID NO: 1105), AAGguauaua (SEQ ID NO: 242), AAGgucugga (SEQ ID NO: 314), CAGguacgca (SEQ ID NO: 1181), AGGgugcggg (SEQ ID NO: 3389), AUGguaagug (SEQ ID NO: 900), AAAgugauga (SEQ ID NO: 3390), UGCgugagua (SEQ ID NO: 3391), AGAguaggga (SEQ ID NO: 684), UGUguaggua (SEQ ID NO: 2912), UAGguaggau (SEQ ID NO: 2521), UAAgugagug (SEQ ID NO: 2440), GCUguaagua (SEQ ID NO: 2193), GAAguaagaa (SEQ ID NO: 1814), UCGgugaggc (SEQ ID NO: 2733), UAGguauuuu (SEQ ID NO: 2564), AAGguacaca (SEQ ID NO: 3392), AAGguaggua (SEQ ID NO: 227), UGGguagguu (SEQ ID NO: 2854), ACAgcaagua (SEQ ID NO: 541), GAGguaggag (SEQ ID NO: 1931), UGGgugaguu (SEQ ID NO: 2878), GCGgugagau (SEQ ID NO: 3393), CCUguagguu (SEQ ID NO: 3394), CAGgugugua (SEQ ID NO: 1440), CUGguaagcc (SEQ ID NO: 1701), AAGgugauuc (SEQ ID NO: 3395), CAGguagcua (SEQ ID NO: 1208), GUUguaagug (SEQ ID NO: 3396), AUGguaagca (SEQ ID NO: 893), AUAguaggga (SEQ ID NO: 3397), GGGguucgcu (SEQ ID NO: 3398), CCGgucagag (SEQ ID NO: 3399), GUAguaugag (SEQ ID NO: 3400), CGUguaagau (SEQ ID NO: 3401), UGAguaggca (SEQ ID NO: 3402), UCAguaugua (SEQ ID NO: 3403), GAGguaucug (SEQ ID NO: 1954), AGAguauuuu (SEQ ID NO: 3404), AAGguuguag (SEQ ID NO: 3405), AGUguaaguu (SEQ ID NO: 821), CGGguaaguu (SEQ ID NO: 1626), UCGgugcgga (SEQ ID NO: 3406), UAGguaagua (SEQ ID NO: 2491), GAAguuagau (SEQ ID NO: 3407), GCUgugagac (SEQ ID NO: 3408), CAGgcaggua (SEQ ID NO: 3409), CAGguagggg (SEQ ID NO: 1218), UAAguuaaga (SEQ ID NO: 3410), AUGguggguu (SEQ ID NO: 970), UAGguaaguu (SEQ ID NO: 2494), CUGguaaauu (SEQ ID NO: 1690), CCGguaagga (SEQ ID NO: 1577), GAGgcaggca (SEQ ID NO: 3411), CAUguaagug (SEQ ID NO: 1523), AAGgugccua (SEQ ID NO: 3412), UUGguaggga (SEQ ID NO: 2977), AAGguaaaca (SEQ ID NO: 123), CGGgugugag (SEQ ID NO: 3413), GGGgugugag (SEQ ID NO: 3414), UCCguggguc (SEQ ID NO: 3415), ACGguaaauc (SEQ ID NO: 3416), UCAguaggua (SEQ ID NO: 3417), CAGgucagcc (SEQ ID NO: 1278), CAGgcggugg (SEQ ID NO: 3418), CGAguaagcu (SEQ ID NO: 3419), CCCgugagca (SEQ ID NO: 3420), AAAguaauga (SEQ ID NO: 3421), CUGguaagcu (SEQ ID NO: 1702), CGGguaacca (SEQ ID NO: 3422), CAGgucgcac (SEQ ID NO: 3423), GAGguaggcc (SEQ ID NO: 3424), UAGgugagcc (SEQ ID NO: 2591), UAGguaggca (SEQ ID NO: 3425), GCGgugcgug (SEQ ID NO: 3426), AUGgugagua (SEQ ID NO: 961), GGGgugaggg (SEQ ID NO: 2282), GAGgucacac (SEQ ID NO: 3427), CAGguaggcc (SEQ ID NO: 3428), CAAgugcuga (SEQ ID NO: 3429), GUCgucuuca (SEQ ID NO: 3430), CAUguaagaa (SEQ ID NO: 1518), GUAguaagga (SEQ ID NO: 3431), UAGguuugua (SEQ ID NO: 2643), CAAguuagag (SEQ ID NO: 3432), AAGguagagu (SEQ ID NO: 208), AAGgugagau (SEQ ID NO: 338), AAAguaggua (SEQ ID NO: 37), ACAgugaauc (SEQ ID NO: 3433), CAGgugugcg (SEQ ID NO: 1436), CAGgucggcc (SEQ ID NO: 1299), AAGguaguau (SEQ ID NO: 3434), ACUgucaguc (SEQ ID NO: 3435), UCUgcagccu (SEQ ID NO: 3436), CGAguaagug (SEQ ID NO: 3437), AGAguaauua (SEQ ID NO: 3438), AGUgugagug (SEQ ID NO: 837), CCGgugagcg (SEQ ID NO: 3439), AAGguaaccu (SEQ ID NO: 3440), AAGguugugg (SEQ ID NO: 3441), AAGgcauggg (SEQ ID NO: 3442), AAGgucagag (SEQ ID NO: 284), ACGguaaggu (SEQ ID NO: 3443), GGGgugagca (SEQ ID NO: 3444), GAGguugcuu (SEQ ID NO: 3445), AAGguaucgc (SEQ ID NO: 3446), CCGguaaagg (SEQ ID NO: 3447), AAAguuaaug (SEQ ID NO: 3448), UAGguacgag (SEQ ID NO: 2510), ACCguaauua (SEQ ID NO: 3449), GGGguaagga (SEQ ID NO: 2249), CCGguaacgc (SEQ ID NO: 3450), CAGgucagaa (SEQ ID NO: 1275), AAGguacuga (SEQ ID NO: 197), GAGgugacca (SEQ ID NO: 2010), GGGgugagcc (SEQ ID NO: 2277), AAGguacagg (SEQ ID NO: 177), AUGguaauua (SEQ ID NO: 3451), CAGgugagag (SEQ ID NO: 1335), AAGgugacuc (SEQ ID NO: 3452), AUAguaagua (SEQ ID NO: 849), GAGguaaacc (SEQ ID NO: 1869), CAGgugggau (SEQ ID NO: 1405), CAGgugagaa (SEQ ID NO: 1333), AGGguaaaaa (SEQ ID NO: 3453), GAGgugugac (SEQ ID NO: 3454), CACguaagcu (SEQ ID NO: 3455), CAGguccccc (SEQ ID NO: 3456), CAGgucaggu (SEQ ID NO: 3457), CGGguaaguc (SEQ ID NO: 3458), ACGguauggg (SEQ ID NO: 3459), GAUguaaguu (SEQ ID NO: 2123), CAAguaauau (SEQ ID NO: 3460), CAGguugggg (SEQ ID NO: 3461), CCUgugcugg (SEQ ID NO: 3462), AAGguaugau (SEQ ID NO: 256), AGGguagagg (SEQ ID NO: 3463), AAGguggguu (SEQ ID NO: 386), CAGgugugaa (SEQ ID NO: 1430), UUGguaugug (SEQ ID NO: 2988), UUGguaucuc (SEQ ID NO: 2985), GGGgugagug (SEQ ID NO: 2284), CUGgugugug (SEQ ID NO: 1779), AGGguagggc (SEQ ID NO: 3464), GUGgugagua (SEQ ID NO: 3465), CAGguaugua (SEQ ID NO: 1258), AAGguacauu (SEQ ID NO: 181), UUAguaagug (SEQ ID NO: 2934), AAUguauauc (SEQ ID NO: 3466), CUUguaagua (SEQ ID NO: 1793), GAGguuagua (SEQ ID NO: 2087), CAGguaaggu (SEQ ID NO: 1146), CAGguaaugu (SEQ ID NO: 1155), AGGgugaggc (SEQ ID NO: 3467), CAGguauuuc (SEQ ID NO: 1269), CAGgucugga (SEQ ID NO: 1307), GGGgugugcu (SEQ ID NO: 3468), UAGgugagug (SEQ ID NO: 2598), AAUguaaccu (SEQ ID NO: 3469), UAAgugaguc (SEQ ID NO: 2439), CAGgugcacu (SEQ ID NO: 3470), ACGguaagua (SEQ ID NO: 579), GAGguauccu (SEQ ID NO: 3471), UCUguaaguc (SEQ ID NO: 2745), CAGguauuca (SEQ ID NO: 1263), UGUguaagug (SEQ ID NO: 3472), CCAgcaaggc (SEQ ID NO: 3473), GAGgugaagg (SEQ ID NO: 2006), AAUguggggu (SEQ ID NO: 3474), UCGgugcgug (SEQ ID NO: 3475), UUGguaaggc (SEQ ID NO: 3476), GAGguaagug (SEQ ID NO: 3477), AAAguaagau (SEQ ID NO: 14), UAGgucuuuu (SEQ ID NO: 3478), GAGgucugau (SEQ ID NO: 3479), CCAguuagag (SEQ ID NO: 3480), UGGgugaaaa (SEQ ID NO: 3481), AGAguaagau (SEQ ID NO: 662), CAGguaauug (SEQ ID NO: 1158), CAGgccgguc (SEQ ID NO: 3482), CCGguaagag (SEQ ID NO: 3483), GAGgugagcu (SEQ ID NO: 2021), CUGguaagac (SEQ ID NO: 3484), CAGgugagau (SEQ ID NO: 1336), CUGguuuguu (SEQ ID NO: 3485), UGGguaggua (SEQ ID NO: 3486), CAGguuagug (SEQ ID NO: 1457), CAGguguucg (SEQ ID NO: 3487), CGGguagguc (SEQ ID NO: 3488), GUGguacaua (SEQ ID NO: 3489), AAGguacuaa (SEQ ID NO: 194), GAUgugagua (SEQ ID NO: 3490), UGUguaagac (SEQ ID NO: 2904), GAGguagccg (SEQ ID NO: 3491), UAGgugaucu (SEQ ID NO: 3492), CAGguacgug (SEQ ID NO: 1185), CUUgucaguc (SEQ ID NO: 3493), GAGguaucac (SEQ ID NO: 3494), GAGguaauga (SEQ ID NO: 3495), AAGguaacac (SEQ ID NO: 3496), CAGguaaagc (SEQ ID NO: 1123), AAGgcaagua (SEQ ID NO: 3497), CGCgugagcc (SEQ ID NO: 3498), AGUgugcguu (SEQ ID NO: 3499), GAUguaagca (SEQ ID NO: 2118), AAGguaauag (SEQ ID NO: 159), GGAgcaguug (SEQ ID NO: 3500), AGCguaagau (SEQ ID NO: 3501), AAGgucaggc (SEQ ID NO: 290), GAGguauuca (SEQ ID NO: 3502), AAUguaaagu (SEQ ID NO: 3503), CAGguaacaa (SEQ ID NO: 3504), UCGguaggug (SEQ ID NO: 3505), AAAguaaguc (SEQ ID NO: 22), CGGgugcagu (SEQ ID NO: 3506), GGUgugugca (SEQ ID NO: 3507), UGAgugagaa (SEQ ID NO: 2794), CACguguaag (SEQ ID NO: 3508), GUGguuggua (SEQ ID NO: 3509), GCAgccuuga (SEQ ID NO: 3510), CGAgugugau (SEQ ID NO: 3511), CAGguauaua (SEQ ID NO: 3512), UAUguaugug (SEQ ID NO: 2665), CCCgugguca (SEQ ID NO: 3513), AUGguaagac (SEQ ID NO: 890), GAGgugugga (SEQ ID NO: 2074), AGUguauccu (SEQ ID NO: 3514), UGAguguguc (SEQ ID NO: 3515), UGGguaaucu (SEQ ID NO: 3516), AUGgcagguu (SEQ ID NO: 3517), GAGguaagau (SEQ ID NO: 1884), UCAgcagcgu (SEQ ID NO: 3518), AAGgugggau (SEQ ID NO: 378), CGGgugcgcu (SEQ ID NO: 3519), CAGgugucug (SEQ ID NO: 1429), AGCgugguaa (SEQ ID NO: 3520), AAUgugaaug (SEQ ID NO: 3521), UCGgugagac (SEQ ID NO: 3522), UAGguaaagc (SEQ ID NO: 3523), CUGguaaaag (SEQ ID NO: 3524), CCGgugcgga (SEQ ID NO: 3525), CAGguacuca (SEQ ID NO: 3526), CAGguagcaa (SEQ ID NO: 1203), GAAguugagu (SEQ ID NO: 3527), GAGguggagg (SEQ ID NO: 2052), AGGguaugag (SEQ ID NO: 762), UAGguaugcu (SEQ ID NO: 3528), UAGgugagac (SEQ ID NO: 2588), CAGguaauua (SEQ ID NO: 1156), CGUguaagcc (SEQ ID NO: 3529), CUUguaaguu (SEQ ID NO: 1795), AAGguaacuu (SEQ ID NO: 140), UCGgcaaggc (SEQ ID NO: 3530), GAGguucucg (SEQ ID NO: 3531), GAGgugggcg (SEQ ID NO: 2058), AAGgcaugug (SEQ ID NO: 3532), CUGguauguu (SEQ ID NO: 1738), UAAgucauuu (SEQ ID NO: 3533), CAUguaauua (SEQ ID NO: 1525), AAUguaaaga (SEQ ID NO: 3534), UAGgugcuca (SEQ ID NO: 3535), AAGguaaugg (SEQ ID NO: 166), GAGguacuga (SEQ ID NO: 3536), UGGguaagua (SEQ ID NO: 2841), UGGguaaaaa (SEQ ID NO: 3537), AAGgugagcu (SEQ ID NO: 342), UACgugaguu (SEQ ID NO: 3538), AGGgugagcc (SEQ ID NO: 790), CGGgugagga (SEQ ID NO: 3539), UGGgugagag (SEQ ID NO: 2869), GGUguaagcu (SEQ ID NO: 3540), CGGguggguu (SEQ ID NO: 1648), CCAgcuaagu (SEQ ID NO: 3541), AAGguuuguc (SEQ ID NO: 467), GAGguuagac (SEQ ID NO: 2084), GAGguaccuc (SEQ ID NO: 3542), UUUguaaguu (SEQ ID NO: 3041), GAGguuagga (SEQ ID NO: 3543), CAGguaggga (SEQ ID NO: 1216), AGGguaauac (SEQ ID NO: 744), UGCgugugua (SEQ ID NO: 3544), CCAguaacca (SEQ ID NO: 3545), AGGgucuguc (SEQ ID NO: 3546), UGGguaugua (SEQ ID NO: 2860), GUGguaagcu (SEQ ID NO: 2348), CAGguaaccu (SEQ ID NO: 3547), AAGgugaguu (SEQ ID NO: 350), UAGguucgug (SEQ ID NO: 3548), AAAguuagua (SEQ ID NO: 3549), UGGgcaaguc (SEQ ID NO: 2816), AAGgcacagu (SEQ ID NO: 3550), GUUguaaguc (SEQ ID NO: 2401), AAGguuugcc (SEQ ID NO: 462), CUUgcauggg (SEQ ID NO: 3551), GCGgugagua (SEQ ID NO: 3552), GGGguaagcg (SEQ ID NO: 3553), GCCguaagaa (SEQ ID NO: 3554), GAGgucggga (SEQ ID NO: 3555), UUGguauugu (SEQ ID NO: 2990), AGUgugagac (SEQ ID NO: 3556), CUGgugggga (SEQ ID NO: 1770), AGAguaaggu (SEQ ID NO: 668), CCGguggguc (SEQ ID NO: 3557), CAGguauucu (SEQ ID NO: 1264), UGGguaacgu (SEQ ID NO: 3558), UUGgugagag (SEQ ID NO: 3559), UAGguacccu (SEQ ID NO: 3560), GGGgugcguc (SEQ ID NO: 3561), AAGgcaggag (SEQ ID NO: 3562), ACGguacauu (SEQ ID NO: 3563), GAGguaguua (SEQ ID NO: 1946), CAGguauggg (SEQ ID NO: 1256), UUUguguguc (SEQ ID NO: 3053), CAGguacuua (SEQ ID NO: 1194), AUGguauacu (SEQ ID NO: 3564), AGUgugagcc (SEQ ID NO: 833), ACAguaacga (SEQ ID NO: 3565), CUGguaccca (SEQ ID NO: 3566), CAGguaaccc (SEQ ID NO: 3567), GGAguaagua (SEQ ID NO: 3568), GAGgugggug (SEQ ID NO: 2065), ACUguauguc (SEQ ID NO: 3569), ACGgugagua (SEQ ID NO: 606), CUGguaaugu (SEQ ID NO: 3570), AAGguaucag (SEQ ID NO: 247), CAGgugcccc (SEQ ID NO: 1370), AGUgucagug (SEQ ID NO: 3571), AAGguaggag (SEQ ID NO: 218), GGAguaugug (SEQ ID NO: 3572), UUGguauuuu (SEQ ID NO: 2992), CCUguuguga (SEQ ID NO: 3573), UUUguaagaa (SEQ ID NO: 3033), UAGguaacau (SEQ ID NO: 2475), CAGguaagca (SEQ ID NO: 3574), CAGgucacag (SEQ ID NO: 3575), CAGgugugag (SEQ ID NO: 1432), UAGguuugcg (SEQ ID NO: 3576), CUGguaagaa (SEQ ID NO: 1697), ACGguuguau (SEQ ID NO: 3577), AAGguugggg (SEQ ID NO: 446), AAGgugaauu (SEQ ID NO: 329), GGGguuaguu (SEQ ID NO: 3578), ACGguaaggc (SEQ ID NO: 3579), CAGguuuaag (SEQ ID NO: 1496), CUGguaaguu (SEQ ID NO: 1709), GGGgugagag (SEQ ID NO: 3580), UGGguggguu (SEQ ID NO: 2886), GAGguuuguu (SEQ ID NO: 2111), UGGguaaaug (SEQ ID NO: 2826), CAGgcaggcc (SEQ ID NO: 3581), CACgugcagg (SEQ ID NO: 3582), AAGgugagcc (SEQ ID NO: 340), CAAguaagug (SEQ ID NO: 1028), CAGgucaguc (SEQ ID NO: 1282), GCGguauaau (SEQ ID NO: 3583), UAGguaaagu (SEQ ID NO: 3584), UAGguggauu (SEQ ID NO: 3585), GAGgucugga (SEQ ID NO: 3586), UCGgucaguu (SEQ ID NO: 3587), UGGguaacug (SEQ ID NO: 3588), AAGguuugau (SEQ ID NO: 3589), UGUgcuggug (SEQ ID NO: 3590), UGUguaccuc (SEQ ID NO: 3591), UGGguacagu (SEQ ID NO: 2849), AUCgucagcg (SEQ ID NO: 3592), CAGgucuugg (SEQ ID NO: 3593), GAAguuggua (SEQ ID NO: 3594), GAAguaaaga (SEQ ID NO: 3595), UUGguaagcu (SEQ ID NO: 2959), UAGguaccag (SEQ ID NO: 2507), AGGguaucau (SEQ ID NO: 3596), CAGguaaaaa (SEQ ID NO: 1118), ACGguaauuu (SEQ ID NO: 583), AUUguaaguu (SEQ ID NO: 997), GAGguacagu (SEQ ID NO: 1908), CAGgugaaag (SEQ ID NO: 1315), UGGguuguuu (SEQ ID NO: 3597), GGGguaggug (SEQ ID NO: 2259), CAGgugccca (SEQ ID NO: 1369), AGCgugagau (SEQ ID NO: 3598), CCAgugagug (SEQ ID NO: 1565), AGGguagaug (SEQ ID NO: 3599), UGGguguguc (SEQ ID NO: 2888), AUCgcgugag (SEQ ID NO: 3600), AGGguaagcc (SEQ ID NO: 3601), AGGguagcag (SEQ ID NO: 3602), UUCguuuccg (SEQ ID NO: 3603), AAGguaagcg (SEQ ID NO: 147), UGGguaagcc (SEQ ID NO: 2837), CAGguauggc (SEQ ID NO: 3604), UGUguaagua (SEQ ID NO: 2907), AAGguagaga (SEQ ID NO: 3605), ACGguaauaa (SEQ ID NO: 3606), CUGguacggu (SEQ ID NO: 3607), GAGgucacag (SEQ ID NO: 3608), UAUguaaguu (SEQ ID NO: 2656), CUGguacgcc (SEQ ID NO: 3609), CAAguaagau (SEQ ID NO: 1024), CUAgugagua (SEQ ID NO: 1673), CCGguaaccg (SEQ ID NO: 3610), CUUguaaguc (SEQ ID NO: 3611), GUGgugagaa (SEQ ID NO: 2378), ACCguaugua (SEQ ID NO: 3612), GUAguaagug (SEQ ID NO: 2324), UUGgugggua (SEQ ID NO: 3014), CGGguacuuu (SEQ ID NO: 3613), UGGguaaaua (SEQ ID NO: 2825), AGAgugagua (SEQ ID NO: 704), AAGguagguu (SEQ ID NO: 230), AAGguaugcg (SEQ ID NO: 3614), CCUguaggcu (SEQ ID NO: 3615), ACAguagaaa (SEQ ID NO: 3616), CCGguuagua (SEQ ID NO: 3617), CGGguaggcg (SEQ ID NO: 3618), GCAgugagug (SEQ ID NO: 2162), GAGgugaguc (SEQ ID NO: 3619), CUGguagccu (SEQ ID NO: 3620), CAUguaugua (SEQ ID NO: 1533), GAAguaacuu (SEQ ID NO: 3621), GAAguaagau (SEQ ID NO: 3622), AAGguuagau (SEQ ID NO: 417), AAGguaauca (SEQ ID NO: 161), AAUguaugua (SEQ ID NO: 507), UGAguaagau (SEQ ID NO: 2767), AGAgugagca (SEQ ID NO: 703), GUAguucuau (SEQ ID NO: 3623), GAGguaauca (SEQ ID NO: 1898), UAGguaugga (SEQ ID NO: 2548), UAGgugggac (SEQ ID NO: 2612), GAGguacaug (SEQ ID NO: 3624), UGGguaaggc (SEQ ID NO: 3625), CAGguacgcc (SEQ ID NO: 1182), CCAguuacgc (SEQ ID NO: 3626), ACUgugguga (SEQ ID NO: 3627), GAGguaaguc (SEQ ID NO: 1894), AUUguaggug (SEQ ID NO: 3628), ACCgucagug (SEQ ID NO: 3629), AAUgugaggg (SEQ ID NO: 3630), ACUgugagug (SEQ ID NO: 645), UGGguguggu (SEQ ID NO: 3631), AAGguuggga (SEQ ID NO: 445), AAGguuugga (SEQ ID NO: 464), UCCgugagug (SEQ ID NO: 3632), CGGgugagug (SEQ ID NO: 1642), AGAguaagcu (SEQ ID NO: 664), CAGgcaagcu (SEQ ID NO: 3633), UAGguauauu (SEQ ID NO: 2541), AAAguagcag (SEQ ID NO: 3634), GAGguaaccu (SEQ ID NO: 1880), AAGgugggca (SEQ ID NO: 379), AGGgugagua (SEQ ID NO: 795), UGGguaaggu (SEQ ID NO: 2840), CUUgucagug (SEQ ID NO: 3635), UAGgugcgcu (SEQ ID NO: 3636), GAGgcaaauu (SEQ ID NO: 3637), AGGguaccuc (SEQ ID NO: 3638), CAAgugcgua (SEQ ID NO: 3639), AGAguaagac (SEQ ID NO: 660), GUGguaaaua (SEQ ID NO: 3640), GAUguaagcg (SEQ ID NO: 3641), GAGguaaagc (SEQ ID NO: 1871), UAGgugagua (SEQ ID NO: 2596), CAGguaacau (SEQ ID NO: 1130), CCUguacggc (SEQ ID NO: 3642), UAGguauguc (SEQ ID NO: 2552), UAGguccaua (SEQ ID NO: 3643), GAGgugaaaa (SEQ ID NO: 2003), AAAguacuga (SEQ ID NO: 3644), UUGguaagcg (SEQ ID NO: 3645), CAGgcaagcg (SEQ ID NO: 3646), UUUgcagguu (SEQ ID NO: 3647), CAGguuuaua (SEQ ID NO: 3648), CUGguaaagc (SEQ ID NO: 1686), AUGgugagcu (SEQ ID NO: 958), CAGgugguug (SEQ ID NO: 1419), GUAguaaguu (SEQ ID NO: 3649), CAGguaauac (SEQ ID NO: 3650), CAGgcaaggc (SEQ ID NO: 3651), AAGguaauuu (SEQ ID NO: 171), UUUguccgug (SEQ ID NO: 3652), GAGguagguu (SEQ ID NO: 1939), ACCgugagug (SEQ ID NO: 3653), CAAguaagcu (SEQ ID NO: 3654), ACAgugagua (SEQ ID NO: 560), UUGgugagau (SEQ ID NO: 3000), AAGguagucu (SEQ ID NO: 233), CAGguaaagg (SEQ ID NO: 3655), GGGguaugga (SEQ ID NO: 2264), UUUguaagug (SEQ ID NO: 3040), GUGguaagag (SEQ ID NO: 2344), AGUgugaguu (SEQ ID NO: 838), AAGgcaagcg (SEQ ID NO: 3656), UAAgugagua (SEQ ID NO: 2438), AGGgugagug (SEQ ID NO: 797), AGUguacgug (SEQ ID NO: 3657), AGGgugcgua (SEQ ID NO: 3658), GGCgugagcc (SEQ ID NO: 2238), CGAguuauga (SEQ ID NO: 3659), CAGguaaaga (SEQ ID NO: 1122), UUGgugaaga (SEQ ID NO: 3660), AGGguaaugg (SEQ ID NO: 3661), AAGguccaga (SEQ ID NO: 300), AGUgugaguc (SEQ ID NO: 836), CAGguaauuu (SEQ ID NO: 1159), CAGguaacgc (SEQ ID NO: 3662), CUGguacacu (SEQ ID NO: 3663), CUGguuagug (SEQ ID NO: 1782), CAGguacuug (SEQ ID NO: 3664), CACguaagua (SEQ ID NO: 3665), GUGgugcggc (SEQ ID NO: 3666), GAGgucaguu (SEQ ID NO: 3667), AUGguaugcc (SEQ ID NO: 932), AAGgugugug (SEQ ID NO: 405), CUGguggguc (SEQ ID NO: 1772), CAGgugaggc (SEQ ID NO: 1342), AAGguuaguc (SEQ ID NO: 423), AAGguagcug (SEQ ID NO: 215), GAGgucagga (SEQ ID NO: 1983), GUUguaggua (SEQ ID NO: 3668), UGGguacaag (SEQ ID NO: 3669), AUGguaggug (SEQ ID NO: 924), GAGguaagcc (SEQ ID NO: 1886), AUGgcaagua (SEQ ID NO: 3670), AAGguauauu (SEQ ID NO: 245), GCGgugagag (SEQ ID NO: 3671), AAGgugcuuc (SEQ ID NO: 3672), UAGguacauc (SEQ ID NO: 3673), ACUgugguaa (SEQ ID NO: 3674), GAGguaggcu (SEQ ID NO: 1933), GAGguaugca (SEQ ID NO: 3675), AGGguaguuc (SEQ ID NO: 3676), CAGguauccu (SEQ ID NO: 1241), AGGguaaguc (SEQ ID NO: 741), AGGgucaguu (SEQ ID NO: 779), CAGguuggga (SEQ ID NO: 3677), CAGguggaua (SEQ ID NO: 3678), GGAguagguu (SEQ ID NO: 2220), GAGguaggau (SEQ ID NO: 3679), GGGguuugug (SEQ ID NO: 3680), UAGguaauug (SEQ ID NO: 3681), AAGguaaccc (SEQ ID NO: 136), ACGguaagaa (SEQ ID NO: 3682), GAGguagggg (SEQ ID NO: 1936), CGAguaggug (SEQ ID NO: 1619), UCCguaagug (SEQ ID NO: 2710), UCGguacagg (SEQ ID NO: 3683), CAAguaagcg (SEQ ID NO: 3684), AAGguccgcg (SEQ ID NO: 3685), AAUgugagua (SEQ ID NO: 523), CAGgugaaug (SEQ ID NO: 3686), GUGguaaggc (SEQ ID NO: 2350), AGAgugagug (SEQ ID NO: 706), UCUguauguc (SEQ ID NO: 3687), UGGgugaguc (SEQ ID NO: 2876), UCGguuagua (SEQ ID NO: 3688), GAUguaugca (SEQ ID NO: 3689), GAGguuggug (SEQ ID NO: 3690), GAGguggggc (SEQ ID NO: 2061), UGGgucaguc (SEQ ID NO: 3691), GCAgugagua (SEQ ID NO: 2161), CAGguugcuu (SEQ ID NO: 3692), AGGguagagu (SEQ ID NO: 3693), UAGgucaggu (SEQ ID NO: 2567), CGCguaugua (SEQ ID NO: 3694), GAGguauuaa (SEQ ID NO: 3695), CAGguaaacu (SEQ ID NO: 3696), AAAguaaguu (SEQ ID NO: 24), GGGgucuggc (SEQ ID NO: 3697), GCUguggggu (SEQ ID NO: 3698), UUGguaaguc (SEQ ID NO: 3699), AAGguagaag (SEQ ID NO: 3700), AAUgugaguc (SEQ ID NO: 524), AAGgucagcu (SEQ ID NO: 288), AAGguaagag (SEQ ID NO: 143), AUGgugagga (SEQ ID NO: 3701), AAGguacuuc (SEQ ID NO: 200), AAGguaagaa (SEQ ID NO: 141), CCGguacagc (SEQ ID NO: 3702), GCGgugcgga (SEQ ID NO: 3703), CAGguacaua (SEQ ID NO: 1168), CUGgugagga (SEQ ID NO: 1755), CUGguaggug (SEQ ID NO: 1731), AACguagguu (SEQ ID NO: 3704), AUGgugugug (SEQ ID NO: 975), UUGguacuau (SEQ ID NO: 3705), CAGgucggug (SEQ ID NO: 1300), CAGgcauggg (SEQ ID NO: 3706), AUGguaucuu (SEQ ID NO: 929), AAGguaacua (SEQ ID NO: 137), CAGgugggcg (SEQ ID NO: 3707), CACgugagga (SEQ ID NO: 3708), AAGgugguuc (SEQ ID NO: 392), UGGgcauucu (SEQ ID NO: 3709), AUGguaagcc (SEQ ID NO: 894), AGGgucagug (SEQ ID NO: 778), AGAguacgua (SEQ ID NO: 3710), AAGguaggca (SEQ ID NO: 220), AAGguauuca (SEQ ID NO: 3711), CAGguagauu (SEQ ID NO: 1202), GAGguauuua (SEQ ID NO: 1972), GAGgucuaca (SEQ ID NO: 3712), GUUguagguc (SEQ ID NO: 3713), CAGguacucg (SEQ ID NO: 3714), GUCguauguu (SEQ ID NO: 3715), AAGguacuuu (SEQ ID NO: 202), AGAgugagau (SEQ ID NO: 702), AGUguuggua (SEQ ID NO: 3716), AAUgugagug (SEQ ID NO: 525), AAGguagauu (SEQ ID NO: 3717), AUGguuugua (SEQ ID NO: 988), GAGgccccag (SEQ ID NO: 3718), AUGgucaguu (SEQ ID NO: 3719), UCUguaagga (SEQ ID NO: 3720), CAGgucgggc (SEQ ID NO: 3721), CAGguaagcc (SEQ ID NO: 1142), UAGgucagug (SEQ ID NO: 2569), AGAguaggaa (SEQ ID NO: 683), CUGguacuuc (SEQ ID NO: 3722), CUCguaagca (SEQ ID NO: 1674), CAGguaacua (SEQ ID NO: 1134), CAGguggcug (SEQ ID NO: 1401), UGGguccgua (SEQ ID NO: 3723), GAGguugugc (SEQ ID NO: 3724), CAGgugcgcg (SEQ ID NO: 1377), AAAguauggc (SEQ ID NO: 3725), UGAguacgua (SEQ ID NO: 2779), CUGguacgga (SEQ ID NO: 3726), CAAgugaccu (SEQ ID NO: 3727), AAGgugaugu (SEQ ID NO: 356), AAGgucugca (SEQ ID NO: 3728), AAAguuugua (SEQ ID NO: 75), AAGgugagca (SEQ ID NO: 339), GAUguaagcc (SEQ ID NO: 2119), CAAguaauuu (SEQ ID NO: 1035), CAGgugugug (SEQ ID NO: 1442), UGGgugaggg (SEQ ID NO: 2874), AAGgugaccu (SEQ ID NO: 3729), UAGgugugag (SEQ ID NO: 2621), CAGgcagguc (SEQ ID NO: 3730), UCAguaaguu (SEQ ID NO: 2692), UCAgcaguga (SEQ ID NO: 3731), AAGguaccac (SEQ ID NO: 3732), UAAguaggug (SEQ ID NO: 3733), AAGgucagcc (SEQ ID NO: 286), CAGguaacuc (SEQ ID NO: 1135), AAAguaagag (SEQ ID NO: 13), AAGguagaua (SEQ ID NO: 209), AAGgcaaggg (SEQ ID NO: 99), CAGgugucgg (SEQ ID NO: 3734), CAGguggcua (SEQ ID NO: 3735), GAGguugcca (SEQ ID NO: 3736), CAGgccgugg (SEQ ID NO: 3737), UUGguauaug (SEQ ID NO: 3738), GAGguugagu (SEQ ID NO: 3739), GAGguagguc (SEQ ID NO: 3740), GUGguaagac (SEQ ID NO: 2343), UAGguccuuc (SEQ ID NO: 3741), GAGgcaaguc (SEQ ID NO: 3742), GAGguaacau (SEQ ID NO: 3743), CAGguauauc (SEQ ID NO: 1236), UCGguugguu (SEQ ID NO: 3744), CAGgugaacc (SEQ ID NO: 3745), CAGgucuuuu (SEQ ID NO: 3746), CAGgcauggc (SEQ ID NO: 3747), AAAguacuug (SEQ ID NO: 32), CAGgugauuc (SEQ ID NO: 1356), UUGguagguu (SEQ ID NO: 3748), UAUgugagca (SEQ ID NO: 3749), CAGgugagcg (SEQ ID NO: 1339), AAUguaauaa (SEQ ID NO: 3750), AAAguaaggc (SEQ ID NO: 3751), UAGguuuguc (SEQ ID NO: 2644), UAGgugggag (SEQ ID NO: 2613), GAGguaaguu (SEQ ID NO: 3752), AAGguagccg (SEQ ID NO: 3753), CAGguggugc (SEQ ID NO: 3754), UGAgucaguu (SEQ ID NO: 3755), CUGguaggcc (SEQ ID NO: 3756), CAAguaagga (SEQ ID NO: 3757), CGGguaaggc (SEQ ID NO: 3758), AAGgcgagga (SEQ ID NO: 3759), CAGguaguuc (SEQ ID NO: 1230), CAGguaagga (SEQ ID NO: 1143), CCUgugagug (SEQ ID NO: 1610), AAGguaaaug (SEQ ID NO: 132), CCGguaauua (SEQ ID NO: 3760), CAGguaaguu (SEQ ID NO: 1149), AAGgugguca (SEQ ID NO: 3761), CAGguaccuc (SEQ ID NO: 1177), AUCguaagua (SEQ ID NO: 3762), CCGguacaua (SEQ ID NO: 3763), GCGgugagug (SEQ ID NO: 3764), GAGgugguau (SEQ ID NO: 2067), CUGgugugga (SEQ ID NO: 3765), GAGguaauuc (SEQ ID NO: 3766), CAAguacgua (SEQ ID NO: 3767), UCUguaagug (SEQ ID NO: 2746), AAUguaagug (SEQ ID NO: 491), AGGgucuguu (SEQ ID NO: 783), GAGguacugc (SEQ ID NO: 1918), AGGguaaggc (SEQ ID NO: 738), AAGgcaagag (SEQ ID NO: 95), CAGguggguu (SEQ ID NO: 1416), UAGguuagga (SEQ ID NO: 3768), UGAguaagcu (SEQ ID NO: 2769), AGAguaagag (SEQ ID NO: 661), AUGgcaggug (SEQ ID NO: 3769), UAGgcaagua (SEQ ID NO: 3770), AUGguaggua (SEQ ID NO: 923), GCAgcccgca (SEQ ID NO: 3771), ACGguaaacu (SEQ ID NO: 3772), AGGgugaguu (SEQ ID NO: 798), GUAguagucu (SEQ ID NO: 3773), GUGgcugaaa (SEQ ID NO: 3774), CAGguuaguc (SEQ ID NO: 1456), CUGgugagca (SEQ ID NO: 1753), UCAguaagug (SEQ ID NO: 2691), AAAgugauug (SEQ ID NO: 3775), UAGgucugga (SEQ ID NO: 3776), GAGguguuuc (SEQ ID NO: 3777), AAGguaaauu (SEQ ID NO: 133), CAUguacauc (SEQ ID NO: 3778), AAGguuugaa (SEQ ID NO: 3779), CCAgcaagug (SEQ ID NO: 3780), UAGguaauaa (SEQ ID NO: 3781), GAGgcaagug (SEQ ID NO: 1859), CAAgugauuc (SEQ ID NO: 1071), CAGgucgugg (SEQ ID NO: 3782), GAAguaugcc (SEQ ID NO: 3783), UCGgugcccu (SEQ ID NO: 3784), GAGgucaguc (SEQ ID NO: 3785), CAGgugagac (SEQ ID NO: 1334), UUUgucugua (SEQ ID NO: 3786), CAGguagaua (SEQ ID NO: 3787), UGGguaucag (SEQ ID NO: 3788), UAGgugggcu (SEQ ID NO: 2616), AUGgugagau (SEQ ID NO: 3789), CAGguaacac (SEQ ID NO: 3790), CCGguauccu (SEQ ID NO: 3791), UAGguaagcu (SEQ ID NO: 2487), UCAguacauc (SEQ ID NO: 3792), UAGguuugcc (SEQ ID NO: 2642), AUGguaagaa (SEQ ID NO: 889), UUGguaagac (SEQ ID NO: 3793), CCGguuaguc (SEQ ID NO: 3794), GAGguaagaa (SEQ ID NO: 1882), UGGguaaguu (SEQ ID NO: 2844), CCGgugagaa (SEQ ID NO: 1585), CCUgugaggg (SEQ ID NO: 1608), ACGguaggag (SEQ ID NO: 590), ACAguauguc (SEQ ID NO: 3795), CAGguauuaa (SEQ ID NO: 3796), CAGguggauc (SEQ ID NO: 3797), AGAgugcgua (SEQ ID NO: 3798), AAGgugaccg (SEQ ID NO: 3799), AGAguaggug (SEQ ID NO: 687), ACUguaugua (SEQ ID NO: 3800), UAGgucaauu (SEQ ID NO: 3801), AGUguguaag (SEQ ID NO: 3802), CGGguaccuu (SEQ ID NO: 3803), CUAgugaguu (SEQ ID NO: 3804), CUAguaagug (SEQ ID NO: 1666), CAGguacaac (SEQ ID NO: 3805), UAGgugugug (SEQ ID NO: 2627), CAUguacggc (SEQ ID NO: 3806), AUGgugugag (SEQ ID NO: 3807), AGGguggaag (SEQ ID NO: 3808), CAGgugcgag (SEQ ID NO: 3809), UAGgugcucc (SEQ ID NO: 3810), AAGguggugg (SEQ ID NO: 390), AAGgucuguu (SEQ ID NO: 317), CAGgugggcc (SEQ ID NO: 1407), AAGgucaguc (SEQ ID NO: 294), CAGguuuuua (SEQ ID NO: 3811), AACgugaggu (SEQ ID NO: 3812), CGGguaagag (SEQ ID NO: 3813), UUUgucggua (SEQ ID NO: 3814), UAGguuaagu (SEQ ID NO: 3815), GUGguaagaa (SEQ ID NO: 2342), CAGguauugg (SEQ ID NO: 1266), GCUguaaguu (SEQ ID NO: 2196), CUAguaagua (SEQ ID NO: 1664), UCGguaaaua (SEQ ID NO: 3816), CAGguaacuu (SEQ ID NO: 1137), CCUgugagua (SEQ ID NO: 3817), CAGguuauau (SEQ ID NO: 3818), CUGgugaaca (SEQ ID NO: 3819), AAGguauaaa (SEQ ID NO: 238), GAGguaagca (SEQ ID NO: 1885), AAGgugaagc (SEQ ID NO: 324), CAGgugaguu (SEQ ID NO: 1348), UUUgugagua (SEQ ID NO: 3820), CUUguacgcc (SEQ ID NO: 3821), AGAguaagug (SEQ ID NO: 670), UGGguaggug (SEQ ID NO: 2853), UGAgcccugc (SEQ ID NO: 3822), UGUguaugua (SEQ ID NO: 3823), AAGguagagg (SEQ ID NO: 3824), GAGguggggg (SEQ ID NO: 2062), UAGguaauuc (SEQ ID NO: 2502), AAGgcauggu (SEQ ID NO: 3825), AGAguaagca (SEQ ID NO: 663), AAGguaggaa (SEQ ID NO: 217), CAAguaagua (SEQ ID NO: 1026), ACUguaauug (SEQ ID NO: 3826), CAGgucugug (SEQ ID NO: 1311), UCGguaccga (SEQ ID NO: 3827), CUGgugagag (SEQ ID NO: 3828), AAGguuugcu (SEQ ID NO: 463), AUGguaccac (SEQ ID NO: 3829), UAAguuaguu (SEQ ID NO: 3830), CAGguaggac (SEQ ID NO: 1213), AGAgugaggc (SEQ ID NO: 3831), CGAgucagua (SEQ ID NO: 3832), CAGgucugag (SEQ ID NO: 1304), GAGguggugg (SEQ ID NO: 3833), ACGguauugg (SEQ ID NO: 3834), GCUgcgagua (SEQ ID NO: 3835), CUGguaagug (SEQ ID NO: 1708), GUGgugagau (SEQ ID NO: 2379), GGGguuugau (SEQ ID NO: 3836), UCUgugagug (SEQ ID NO: 2762), CUUgucagua (SEQ ID NO: 1801), GAGguaaaac (SEQ ID NO: 1866), UCUguaagau (SEQ ID NO: 2741), CCAguaaguu (SEQ ID NO: 1558), CAGguaaagu (SEQ ID NO: 1124), GCGgugagca (SEQ ID NO: 2179), UAAguaagag (SEQ ID NO: 2416), CUGgcaggug (SEQ ID NO: 3837), GAGguaaggg (SEQ ID NO: 1891), UGAguaaguu (SEQ ID NO: 2775), GAGgugagac (SEQ ID NO: 2015), GCUgucuguu (SEQ ID NO: 3838), AAGguaacaa (SEQ ID NO: 134), GAGguaacgg (SEQ ID NO: 3839), CUGguauucu (SEQ ID NO: 3840), CAAguaacug (SEQ ID NO: 1021), AAGguggggu (SEQ ID NO: 383), UAGguauggc (SEQ ID NO: 2549), CAGguauuuu (SEQ ID NO: 1271), GUGguaaacu (SEQ ID NO: 3841), GAGgucugag (SEQ ID NO: 1998), CUGguaaggu (SEQ ID NO: 1706), CAAguaaguu (SEQ ID NO: 1029), AAGguagacc (SEQ ID NO: 206), GAGgcgagcg (SEQ ID NO: 3842), CUGguaaaua (SEQ ID NO: 1687), UGUguaagcg (SEQ ID NO: 3843), CAGguuaggg (SEQ ID NO: 1453), GGGgugagga (SEQ ID NO: 2280), ACAguaugug (SEQ ID NO: 3844), CCGgugggga (SEQ ID NO: 3845), GAGgucagug (SEQ ID NO: 3846), AGGguaaggu (SEQ ID NO: 3847), ACAguaagua (SEQ ID NO: 546), GGUguaaggu (SEQ ID NO: 3848), GAGguaauaa (SEQ ID NO: 1895), CAGguauucc (SEQ ID NO: 3849), CUGguauaaa (SEQ ID NO: 3850), CCGgucugug (SEQ ID NO: 3851), CAGguaacug (SEQ ID NO: 1136), GCAguaagua (SEQ ID NO: 2147), AAGguagggg (SEQ ID NO: 225), CAAguccacc (SEQ ID NO: 3852), CAAguuggug (SEQ ID NO: 3853), CAGgugcggu (SEQ ID NO: 1379), CAGguaaaau (SEQ ID NO: 3854), ACGguaagga (SEQ ID NO: 3855), UGGguaauaa (SEQ ID NO: 3856), UAGguaagug (SEQ ID NO: 2493), CCGguagguu (SEQ ID NO: 3857), AGAguaugga (SEQ ID NO: 3858), CUCgugaguc (SEQ ID NO: 3859), AAAgccggug (SEQ ID NO: 3860), UUGguaauuu (SEQ ID NO: 2970), GAGguaaaag (SEQ ID NO: 1867), CCUgugugag (SEQ ID NO: 3861), AAAguaagga (SEQ ID NO: 18), UGAgugagug (SEQ ID NO: 2800), AAGguacaug (SEQ ID NO: 180), CCGguaaaug (SEQ ID NO: 3862), CAGgugaagc (SEQ ID NO: 3863), CAGguacccg (SEQ ID NO: 1173), GAGguaaggc (SEQ ID NO: 1890), UUUguauguu (SEQ ID NO: 3049), CAGgugcucc (SEQ ID NO: 1386), UCGguagguc (SEQ ID NO: 3864), CGGgugaggc (SEQ ID NO: 3865), AAGguaauua (SEQ ID NO: 168), ACUgugaguc (SEQ ID NO: 644), AAGgucagca (SEQ ID NO: 285), GUGgugagug (SEQ ID NO: 2384), CAUguccacc (SEQ ID NO: 3866), AAGgugaccc (SEQ ID NO: 3867), CGGguuagua (SEQ ID NO: 3868), GCGguaguaa (SEQ ID NO: 3869), GCUguaggua (SEQ ID NO: 3870), CCUguugagu (SEQ ID NO: 3871), UAGgucuggc (SEQ ID NO: 2577), GAUgugagcc (SEQ ID NO: 2131), CUUgugagua (SEQ ID NO: 1802), CUGguguguu (SEQ ID NO: 1780), GAGgcaugug (SEQ ID NO: 1863), CAGgcaagag (SEQ ID NO: 1101), UUGguaagaa (SEQ ID NO: 2957), GAGguguggg (SEQ ID NO: 2075), GAGguauuuu (SEQ ID NO: 1975), CAGguaguaa (SEQ ID NO: 1224), AGGguaagac (SEQ ID NO: 3872), UUUguaggca (SEQ ID NO: 3873), AGGgugagau (SEQ ID NO: 3874), GAGguuugua (SEQ ID NO: 2110), AAGgugagug (SEQ ID NO: 349), GAGgugggag (SEQ ID NO: 2055), AAGgugagaa (SEQ ID NO: 335), CUGguaagag (SEQ ID NO: 1698), AUAguaaaga (SEQ ID NO: 3875), GAUgugaguc (SEQ ID NO: 2134), AAGgugcagg (SEQ ID NO: 3876), CAGgucuguc (SEQ ID NO: 1310), GAGgugauuu (SEQ ID NO: 3877), CAGguuggcu (SEQ ID NO: 3878), CGGguauggg (SEQ ID NO: 3879), AUGguccauc (SEQ ID NO: 3880), CCGguuggug (SEQ ID NO: 3881), GGAguaaguc (SEQ ID NO: 3882), AAUguaagga (SEQ ID NO: 488), CAGguuuguu (SEQ ID NO: 1510), UAGgugugua (SEQ ID NO: 2626), UAUgucuuug (SEQ ID NO: 3883), ACGguacuuc (SEQ ID NO: 3884), AAGgcacgcg (SEQ ID NO: 3885), CUGguaaacc (SEQ ID NO: 1684), CUUgugggua (SEQ ID NO: 3886), UGAguaaguc (SEQ ID NO: 2773), CUGgugggug (SEQ ID NO: 1773), GAGguggaga (SEQ ID NO: 3887), GUGguggcug (SEQ ID NO: 3888), GUGguaagug (SEQ ID NO: 2353), AACgugagua (SEQ ID NO: 3889), GAAgcuguaa (SEQ ID NO: 3890), CGGguaucuu (SEQ ID NO: 3891), CAGgugucag (SEQ ID NO: 1424), AAUguacgca (SEQ ID NO: 3892), CCGgugggua (SEQ ID NO: 3893), UGGgugaggu (SEQ ID NO: 3894), AAGguauguu (SEQ ID NO: 266), CAGguauguu (SEQ ID NO: 1261), CAGguuugcu (SEQ ID NO: 1505), UUGguaaguu (SEQ ID NO: 2964), CAGguaguug (SEQ ID NO: 1231), CCUgugaaua (SEQ ID NO: 3895), GCUgugugug (SEQ ID NO: 3896), CAAguaauuc (SEQ ID NO: 1033), AGGguaaugu (SEQ ID NO: 3897), GCUgugaguc (SEQ ID NO: 2205), ACCguaaguu (SEQ ID NO: 3898), CGUguaagua (SEQ ID NO: 3899), GGGguaaguc (SEQ ID NO: 3900), AAUguaugau (SEQ ID NO: 3901), AAUgugauua (SEQ ID NO: 3902), UCAguaagaa (SEQ ID NO: 2682), CAGguccguc (SEQ ID NO: 3903), GAAguauuga (SEQ ID NO: 3904), UUGguaagga (SEQ ID NO: 2960), CAGgucgguu (SEQ ID NO: 3905), UAGguuagug (SEQ ID NO: 2635), ACGguaaaac (SEQ ID NO: 577), AAGguagguc (SEQ ID NO: 228), UACgugagua (SEQ ID NO: 3906), UUGguaagca (SEQ ID NO: 3907), GCGgugaguc (SEQ ID NO: 3908), GAAguaaggg (SEQ ID NO: 3909), CGCgugaguu (SEQ ID NO: 3910), CAGguacccc (SEQ ID NO: 3911), UCUguaagac (SEQ ID NO: 3912), GAGgugggca (SEQ ID NO: 2057), AAUguaagac (SEQ ID NO: 3913), CAGgcaaggg (SEQ ID NO: 3914), CAAguaacua (SEQ ID NO: 1020), AAAguuuguc (SEQ ID NO: 3915), CAGguacugu (SEQ ID NO: 1193), AAGgucccuc (SEQ ID NO: 303), UCGguaaguc (SEQ ID NO: 3916), UGGgugagug (SEQ ID NO: 2877), CUUgugagau (SEQ ID NO: 3917), AGAgugagcu (SEQ ID NO: 3918), UAAgugggga (SEQ ID NO: 3919), UAGguaggga (SEQ ID NO: 2522), CAGguuagcc (SEQ ID NO: 1452), AGGguaauca (SEQ ID NO: 3920), AAGguucagc (SEQ ID NO: 3921), UGGgugggug (SEQ ID NO: 2885), CAGguuguga (SEQ ID NO: 1494), AAGguaagug (SEQ ID NO: 155), CAUgugcgua (SEQ ID NO: 1543), CCGguauauu (SEQ ID NO: 3922), ACCguaugug (SEQ ID NO: 3923), CAGguauagu (SEQ ID NO: 3924), CAGguauuac (SEQ ID NO: 3925), CAGgugcagg (SEQ ID NO: 1364), GUGgugagcu (SEQ ID NO: 2381), AAGguaacau (SEQ ID NO: 135), CUGgugaugg (SEQ ID NO: 3926), AUGguaaaug (SEQ ID NO: 882), CCGgugagca (SEQ ID NO: 3927), AAGguaaacc (SEQ ID NO: 124), AAGguacugg (SEQ ID NO: 3928), GCGgucagga (SEQ ID NO: 3929), CUGgucaggg (SEQ ID NO: 3930), AAAguacguu (SEQ ID NO: 3931), AGAguagguu (SEQ ID NO: 688), AGGguaagcu (SEQ ID NO: 3932), AUUgugagua (SEQ ID NO: 1009), CCGgccacca (SEQ ID NO: 3933), GAGguaacuu (SEQ ID NO: 1881), GAGguaugaa (SEQ ID NO: 1956), CAGgucagac (SEQ ID NO: 1276), UAGgcgugug (SEQ ID NO: 2462), AGGguaaguu (SEQ ID NO: 743), CAGgcaugag (SEQ ID NO: 1111), CAGguaacgu (SEQ ID NO: 1133), CAGgcgagca (SEQ ID NO: 3934), UAGguauggu (SEQ ID NO: 2550), AGAguaggau (SEQ ID NO: 3935), CUGguuucaa (SEQ ID NO: 3936), GAGguaaacu (SEQ ID NO: 3937), CAGgcaugca (SEQ ID NO: 1112), UUGguaaucu (SEQ ID NO: 3938), AGGgcagaau (SEQ ID NO: 3939), AUGguaaaac (SEQ ID NO: 877), GCUgcaggug (SEQ ID NO: 3940), GAAgcacgug (SEQ ID NO: 3941), CAUguaaaca (SEQ ID NO: 3942), UGGguaagau (SEQ ID NO: 2835), AGGguagcua (SEQ ID NO: 3943), AGGguggggu (SEQ ID NO: 800), CCUguaaguu (SEQ ID NO: 1600), UGAgugaguu (SEQ ID NO: 2801), GGAguaugua (SEQ ID NO: 3944), CAGgugaccu (SEQ ID NO: 1328), AAAguacgga (SEQ ID NO: 3945), GAGguacaga (SEQ ID NO: 1906), GAUguaggua (SEQ ID NO: 2125), GGGguaauug (SEQ ID NO: 3946), UAGguggguu (SEQ ID NO: 2617), GUGguacgua (SEQ ID NO: 3947), AAGguacagc (SEQ ID NO: 3948), GAGgugaaga (SEQ ID NO: 3949), GGGguaagca (SEQ ID NO: 2246), UGAguagguc (SEQ ID NO: 3950), GGGguaaguu (SEQ ID NO: 2253), AUUgugaguu (SEQ ID NO: 1011), UCAguaagac (SEQ ID NO: 3951), AGUgugagcu (SEQ ID NO: 834), AAGgcaaaac (SEQ ID NO: 3952), CUGgugaguc (SEQ ID NO: 1760), AAGgucucug (SEQ ID NO: 310), GAGgcugugc (SEQ ID NO: 3953), AGAgugagac (SEQ ID NO: 700), GAGgugaugu (SEQ ID NO: 2033), AGAguauggu (SEQ ID NO: 3954), UGGguggguc (SEQ ID NO: 2884), GCUgcugagc (SEQ ID NO: 3955), CAGguagcug (SEQ ID NO: 1210), UAGgucagaa (SEQ ID NO: 3956), CCGguaggug (SEQ ID NO: 3957), GCAguaugau (SEQ ID NO: 3958), CAGguuucag (SEQ ID NO: 3959), GAGguuugcc (SEQ ID NO: 3960), GGGguggggg (SEQ ID NO: 3961), AAGguacaua (SEQ ID NO: 179), UGGguguguu (SEQ ID NO: 2890), AGAguaaggc (SEQ ID NO: 666), GCGguuagug (SEQ ID NO: 3962), AAGgugacuu (SEQ ID NO: 334), AUGguaagau (SEQ ID NO: 892), AUGguaguug (SEQ ID NO: 3963), CAUguaagac (SEQ ID NO: 3964), CUGguaugua (SEQ ID NO: 1736), UUCguaagga (SEQ ID NO: 3965), GAAguaugac (SEQ ID NO: 3966), CGGguaauuc (SEQ ID NO: 1627), UGGguaacuu (SEQ ID NO: 2831), CAGgugccua (SEQ ID NO: 1372), CAUguagggc (SEQ ID NO: 3967), ACCgucagga (SEQ ID NO: 3968), CGUguucgau (SEQ ID NO: 3969), GAGgcaggac (SEQ ID NO: 3970), UAGguaauau (SEQ ID NO: 2496), UCGguauacu (SEQ ID NO: 3971), UAGguugugc (SEQ ID NO: 3972), CCGgugaguc (SEQ ID NO: 3973), CAGgugccaa (SEQ ID NO: 1368), CAGgugaugc (SEQ ID NO: 1352), AAGgugagga (SEQ ID NO: 343), GUGgugaggg (SEQ ID NO: 3974), UGGgucagua (SEQ ID NO: 3975), GAGgucaggg (SEQ ID NO: 1985), UAGguacgua (SEQ ID NO: 2511), GAGgcaagag (SEQ ID NO: 1857), CCUguuggua (SEQ ID NO: 3976), GAGguaucca (SEQ ID NO: 3977), UAAguaagcu (SEQ ID NO: 2419), AAGgucaguu (SEQ ID NO: 296), AAAguuaaag (SEQ ID NO: 3978), GAGgugcuau (SEQ ID NO: 3979), ACGguaaguu (SEQ ID NO: 581), CUGgugaggg (SEQ ID NO: 1757), GAGguuaugu (SEQ ID NO: 2091), CUUgugugca (SEQ ID NO: 3980), UGAgcugggg (SEQ ID NO: 3981), AAGguauagu (SEQ ID NO: 3982), UAGguaaaac (SEQ ID NO: 2464), GGGgugaggu (SEQ ID NO: 3983), GAGgcaagca (SEQ ID NO: 3984), GGAguaacgu (SEQ ID NO: 3985), AGAguaagua (SEQ ID NO: 3986), AAAguaagua (SEQ ID NO: 21), GAGgcaacca (SEQ ID NO: 3987), UGUguaaguu (SEQ ID NO: 2909), UAGgugaggc (SEQ ID NO: 2594), ACAguaagaa (SEQ ID NO: 544), UGAguaagug (SEQ ID NO: 2774), CAAgucagua (SEQ ID NO: 1057), AGGguaaaug (SEQ ID NO: 3988), AAGguaugca (SEQ ID NO: 257), GCUgugcgug (SEQ ID NO: 3989), GAGguucgcc (SEQ ID NO: 3990), AAGgcuugca (SEQ ID NO: 3991), CAGgcaagug (SEQ ID NO: 1104), AUAguaaguc (SEQ ID NO: 3992), UUGguaggua (SEQ ID NO: 2978), GCAgcaggua (SEQ ID NO: 3993), AAGguauauc (SEQ ID NO: 243), AGCguaagcc (SEQ ID NO: 3994), CUGguucgaa (SEQ ID NO: 3995), ACGgugggug (SEQ ID NO: 612), CUGgucauug (SEQ ID NO: 3996), CAGgucagga (SEQ ID NO: 1280), CAAgugagac (SEQ ID NO: 1062), GAGguacugg (SEQ ID NO: 1919), GAGguguagu (SEQ ID NO: 3997), GAGguguccu (SEQ ID NO: 3998), CAGgugcgua (SEQ ID NO: 1380), AGUgcccuga (SEQ ID NO: 3999), AUGgugaguc (SEQ ID NO: 962), UGUgugugua (SEQ ID NO: 4000), CAGguaugcu (SEQ ID NO: 1254), CUGguacagu (SEQ ID NO: 4001), UUGguacgua (SEQ ID NO: 4002), UCUguacgua (SEQ ID NO: 4003), UAAguaauuc (SEQ ID NO: 4004), CACguaugug (SEQ ID NO: 4005), CAGgcaagua (SEQ ID NO: 1103), UCGgugagug (SEQ ID NO: 4006), GGUgugaguc (SEQ ID NO: 2315), UCUguaagcu (SEQ ID NO: 2743), AAGguucaga (SEQ ID NO: 4007), AGGguacuuc (SEQ ID NO: 4008), GCGgcagguu (SEQ ID NO: 4009), GAGgcccgug (SEQ ID NO: 4010), CAGguauaaa (SEQ ID NO: 4011), AUGgucaagu (SEQ ID NO: 4012), AAGgugagua (SEQ ID NO: 347), GUGguuuguu (SEQ ID NO: 4013), AGAgugagga (SEQ ID NO: 4014), GAGguaugac (SEQ ID NO: 1957), UAGgcgugag (SEQ ID NO: 4015), AAGguacucc (SEQ ID NO: 4016), UGAgugagga (SEQ ID NO: 2798), GAGguaugau (SEQ ID NO: 4017), GGGgucggua (SEQ ID NO: 4018), ACGguaugca (SEQ ID NO: 4019), CAGguaccac (SEQ ID NO: 1171), UAAguaccug (SEQ ID NO: 4020), AGGgugggcu (SEQ ID NO: 4021), CUGgucuguu (SEQ ID NO: 4022), UAGgucagag (SEQ ID NO: 4023), AAGguguguu (SEQ ID NO: 406), CUGgucagug (SEQ ID NO: 4024), AAGgugggac (SEQ ID NO: 4025), GUGguaguag (SEQ ID NO: 4026), CUAguuuagg (SEQ ID NO: 4027), CCCgccccau (SEQ ID NO: 4028), GCUguacugc (SEQ ID NO: 4029), GAGguaauau (SEQ ID NO: 1897), UAGguuggug (SEQ ID NO: 4030), AAGguccaac (SEQ ID NO: 4031), UAGgugagga (SEQ ID NO: 2593), GUGguaaguu (SEQ ID NO: 2354), AGUgugagag (SEQ ID NO: 831), AAUguacaug (SEQ ID NO: 497), UUGgcaggug (SEQ ID NO: 4032), UAGguuauug (SEQ ID NO: 4033), CAGguacuga (SEQ ID NO: 1191), GCGguggguc (SEQ ID NO: 4034), UGUguaagau (SEQ ID NO: 4035), GAGgugagua (SEQ ID NO: 2025), GCAgccccgg (SEQ ID NO: 4036), CAGgugcuaa (SEQ ID NO: 4037), AGUguaagag (SEQ ID NO: 815), CAGguacauc (SEQ ID NO: 4038), CAGgugggac (SEQ ID NO: 1403), AGGguaaaua (SEQ ID NO: 727), UAAguaauua (SEQ ID NO: 4039), CAGguaaccg (SEQ ID NO: 1132), AAGguuugca (SEQ ID NO: 461), UAGgugguuu (SEQ ID NO: 4040), CAGgugaccg (SEQ ID NO: 1327), UGUguaagcu (SEQ ID NO: 4041), GGAgugaguc (SEQ ID NO: 2227), AGGguaggag (SEQ ID NO: 752), AGGgugggug (SEQ ID NO: 802), AAGgucugag (SEQ ID NO: 313), GAUguaauau (SEQ ID NO: 4042), GGGguaauua (SEQ ID NO: 4043), UAGguaggua (SEQ ID NO: 2524), GAGgcaagua (SEQ ID NO: 1858), GAGguaagga (SEQ ID NO: 1889), UAGguacuac (SEQ ID NO: 4044), UCGgugggug (SEQ ID NO: 4045), AAGgugugga (SEQ ID NO: 401), CAGgucugcc (SEQ ID NO: 1305), UAAgugagcc (SEQ ID NO: 4046), GAAguaaguu (SEQ ID NO: 1820), GAAguaagcc (SEQ ID NO: 1815), UAGgugcgac (SEQ ID NO: 4047), GAGguauggc (SEQ ID NO: 4048), GCAguaagaa (SEQ ID NO: 2145), CAGgugugga (SEQ ID NO: 1438), UUGguaacgu (SEQ ID NO: 4049), GCUguaaaaa (SEQ ID NO: 4050), UUGguuagua (SEQ ID NO: 4051), AUAguaaggg (SEQ ID NO: 4052), UUGguacuag (SEQ ID NO: 4053), CGGgcagccg (SEQ ID NO: 4054), CAGgugcugg (SEQ ID NO: 1389), UAUgugaguu (SEQ ID NO: 2673), CAGgucuggg (SEQ ID NO: 4055), UAAguaagaa (SEQ ID NO: 2415), AAGguuauua (SEQ ID NO: 4056), AGAguaaagc (SEQ ID NO: 4057), AGAgugugag (SEQ ID NO: 4058), UAGgugcgag (SEQ ID NO: 4059), CAAguaaacg (SEQ ID NO: 4060), AAGguacgua (SEQ ID NO: 4061), CUGgugagua (SEQ ID NO: 1759), CCAguaugua (SEQ ID NO: 4062), UUGgugagug (SEQ ID NO: 3006), UGAguaagua (SEQ ID NO: 2772), GAGguuagca (SEQ ID NO: 4063), GUGguaagcc (SEQ ID NO: 4064), CUGguauggc (SEQ ID NO: 1734), AAAguaacac (SEQ ID NO: 8), CAGguacuaa (SEQ ID NO: 1186), UCUguaaguu (SEQ ID NO: 2747), GAGgugaggg (SEQ ID NO: 2024), ACUgugggua (SEQ ID NO: 647), GAUguuugug (SEQ ID NO: 4065), CAGgugucaa (SEQ ID NO: 4066), CAGgucacca (SEQ ID NO: 4067), CCGgugagua (SEQ ID NO: 4068), UUGguaaaua (SEQ ID NO: 4069), CAGguggggg (SEQ ID NO: 1411), ACUgcaggug (SEQ ID NO: 4070), UAGguauguu (SEQ ID NO: 2554), GGAgcaagug (SEQ ID NO: 4071), UCGgugccuc (SEQ ID NO: 4072), CAAguaacuu (SEQ ID NO: 4073), GAGguaacca (SEQ ID NO: 1879), CAGguaauau (SEQ ID NO: 1151), GGAguaagaa (SEQ ID NO: 4074), GAGguaccuu (SEQ ID NO: 1914), AGGguaagga (SEQ ID NO: 737), CCUgugaguc (SEQ ID NO: 1609), GAGguaaugg (SEQ ID NO: 1900), AUGguguguc (SEQ ID NO: 4075), GGGgugagua (SEQ ID NO: 4076), AGGgucaggu (SEQ ID NO: 4077), UGGguaaggg (SEQ ID NO: 2839), AGGguagguu (SEQ ID NO: 759), AUAgugaguu (SEQ ID NO: 4078), CCCguaggcu (SEQ ID NO: 4079), ACAguaugua (SEQ ID NO: 553), GACgugugua (SEQ ID NO: 4080), GCGgugagga (SEQ ID NO: 4081), CAGgugaccc (SEQ ID NO: 1326), UAAguuuagu (SEQ ID NO: 4082), ACAguugagu (SEQ ID NO: 570), CGGgugaggg (SEQ ID NO: 1639), CAGguggauu (SEQ ID NO: 1398), CGGguagagg (SEQ ID NO: 4083), UAGgugcgug (SEQ ID NO: 2608), GGGguaagaa (SEQ ID NO: 2243), GAGguggggu (SEQ ID NO: 4084), CACguggguu (SEQ ID NO: 4085), ACGguaauug (SEQ ID NO: 4086), AGAgugaguc (SEQ ID NO: 705), UUGgcuccaa (SEQ ID NO: 4087), AAGgugaugc (SEQ ID NO: 355), AAGguugguc (SEQ ID NO: 448), AGCguaaguu (SEQ ID NO: 4088), AUUguaugua (SEQ ID NO: 1006), UCAguuaagu (SEQ ID NO: 4089), CAAguacgug (SEQ ID NO: 4090), CAGgugcgug (SEQ ID NO: 1382), CAGguaggua (SEQ ID NO: 1220), AUGguggggu (SEQ ID NO: 4091), AUGgugaguu (SEQ ID NO: 964), CAGguaauca (SEQ ID NO: 4092), AAGguagggu (SEQ ID NO: 226), CAGgccaagg (SEQ ID NO: 4093), GUGgugagag (SEQ ID NO: 4094), AAGguuggug (SEQ ID NO: 449), CAGguacucu (SEQ ID NO: 1190), UAGgcaugug (SEQ ID NO: 4095), UUGguaccuu (SEQ ID NO: 4096), CUGgugugcc (SEQ ID NO: 4097), ACAguugcca (SEQ ID NO: 4098), UUGguaauau (SEQ ID NO: 4099), GAGgugcaug (SEQ ID NO: 4100), UUGguuugua (SEQ ID NO: 3028), UUGguaagug (SEQ ID NO: 2963), UGUgugugug (SEQ ID NO: 4101), GUGguuugua (SEQ ID NO: 2398), GCGguacaca (SEQ ID NO: 4102), AGAguaugcu (SEQ ID NO: 4103), UUUguaagua (SEQ ID NO: 3038), UCUgugcggg (SEQ ID NO: 4104), AAGgucagug (SEQ ID NO: 295), GAGguaggaa (SEQ ID NO: 1930), GCGguuagca (SEQ ID NO: 4105), AGGgugaggg (SEQ ID NO: 793), GAAgugagua (SEQ ID NO: 4106), CAGgugacag (SEQ ID NO: 4107), AAGgugauua (SEQ ID NO: 357), GAGgccagcc (SEQ ID NO: 4108), GAGgucuccu (SEQ ID NO: 4109), UAGguauuac (SEQ ID NO: 2556), CAUguaagag (SEQ ID NO: 1519), CUGguagggc (SEQ ID NO: 4110), GAAguaagua (SEQ ID NO: 1818), CGGguaagug (SEQ ID NO: 4111), CAGguaaucu (SEQ ID NO: 4112), GUGguaggua (SEQ ID NO: 4113), CAGgugggua (SEQ ID NO: 1413), AAGgccagug (SEQ ID NO: 4114), AAAgugaauc (SEQ ID NO: 4115), ACGguuacgu (SEQ ID NO: 4116), AUGguaggaa (SEQ ID NO: 917), CGGgugagac (SEQ ID NO: 4117), GAGguuggaa (SEQ ID NO: 2099), UGGgugagcc (SEQ ID NO: 2871), CCAgugagua (SEQ ID NO: 1564), CUAguacgag (SEQ ID NO: 4118), CAGguaugac (SEQ ID NO: 1248), GCUgugaggu (SEQ ID NO: 4119), CUGguaugaa (SEQ ID NO: 4120), GGUguacgac (SEQ ID NO: 4121), CUUgugagug (SEQ ID NO: 4122), GUGgugagca (SEQ ID NO: 2380), CUGguaacuu (SEQ ID NO: 1696), CAGguacuau (SEQ ID NO: 1188), AGGguaaggg (SEQ ID NO: 739), UUGguuaguu (SEQ ID NO: 3025), GGUguaagca (SEQ ID NO: 2302), UCGgugagga (SEQ ID NO: 4123), UGGguaaaca (SEQ ID NO: 4124), UCGguacgug (SEQ ID NO: 4125), UAGguagcag (SEQ ID NO: 4126), CUGguaaggc (SEQ ID NO: 1704), GUGguaagga (SEQ ID NO: 2349), UAAguaagca (SEQ ID NO: 2418), GAGguuccaa (SEQ ID NO: 4127), CUGguaugga (SEQ ID NO: 4128), GGGgugggua (SEQ ID NO: 2288), CAGguuuccc (SEQ ID NO: 4129), CAGgucucug (SEQ ID NO: 4130), GAGgugagga (SEQ ID NO: 2022), CUUguggguu (SEQ ID NO: 1805), AUGgugagac (SEQ ID NO: 953), CAGgugaagg (SEQ ID NO: 1319), GCGguagggg (SEQ ID NO: 4131), GUUguuuccc (SEQ ID NO: 4132), AAAgcaucca (SEQ ID NO: 4133), GUGguagguu (SEQ ID NO: 2367), AAGgugugaa (SEQ ID NO: 398), CAGguacagu (SEQ ID NO: 1167), AAGguaccaa (SEQ ID NO: 182), UUGguaauug (SEQ ID NO: 2969), AAGgugcuca (SEQ ID NO: 4134), AAGguucaac (SEQ ID NO: 4135), CAGguuuaca (SEQ ID NO: 4136), GCUguaagug (SEQ ID NO: 2195), AGGguauguc (SEQ ID NO: 769), GAGgucgggg (SEQ ID NO: 1996), AAGgugccug (SEQ ID NO: 363), AAGguaaaaa (SEQ ID NO: 119), GUGgugaguu (SEQ ID NO: 2385), UAGguaagaa (SEQ ID NO: 4137), AGGguauccu (SEQ ID NO: 4138), GUGguaauau (SEQ ID NO: 4139), UCUguaagua (SEQ ID NO: 2744), UGGguaugga (SEQ ID NO: 4140), AUGguaugga (SEQ ID NO: 935), GACgugagcc (SEQ ID NO: 1854), CUGguuuggc (SEQ ID NO: 4141), AUGguauauc (SEQ ID NO: 4142), AAAguaaacu (SEQ ID NO: 4143), AGCgugagug (SEQ ID NO: 721), CUGguauaga (SEQ ID NO: 4144), CAGgugggga (SEQ ID NO: 1409), AGAguauguu (SEQ ID NO: 696), UAGguacuug (SEQ ID NO: 4145), GCAguaggug (SEQ ID NO: 4146), AGUguauguc (SEQ ID NO: 4147), AAGguuaagc (SEQ ID NO: 413), CUGguggccu (SEQ ID NO: 4148), GAAgugaguc (SEQ ID NO: 1839), UUGguguaag (SEQ ID NO: 4149), CAGguaagaa (SEQ ID NO: 1138), CGGgucucgg (SEQ ID NO: 4150), GAGgugcaca (SEQ ID NO: 2035), CUCguuaguu (SEQ ID NO: 4151), AAGgugauca (SEQ ID NO: 352), UAUguaagaa (SEQ ID NO: 2649), GAGgugcuug (SEQ ID NO: 2047), CAGgugguca (SEQ ID NO: 4152), ACGguaaguc (SEQ ID NO: 4153), ACAguaaugu (SEQ ID NO: 4154), CCUguaaggu (SEQ ID NO: 4155), GAGguuaagu (SEQ ID NO: 4156), UCGguaugug (SEQ ID NO: 2725), UGGguauguu (SEQ ID NO: 2863), AAGguauuac (SEQ ID NO: 268), CAGgugaggg (SEQ ID NO: 1343), UUGguaaaca (SEQ ID NO: 4157), AAGguagugu (SEQ ID NO: 4158), GAGguguggc (SEQ ID NO: 4159), CAGguacgga (SEQ ID NO: 4160), AAGgucauca (SEQ ID NO: 4161), CAAguaggca (SEQ ID NO: 4162), CAGgugaaac (SEQ ID NO: 4163), CAGguacugc (SEQ ID NO: 1192), AAUgcaagug (SEQ ID NO: 4164), CAUguaauuc (SEQ ID NO: 4165), AAGguaugcu (SEQ ID NO: 259), CUGgugaguu (SEQ ID NO: 1762), CAGgugguuu (SEQ ID NO: 4166), UGUgugagua (SEQ ID NO: 2922), AAGgucggug (SEQ ID NO: 4167), AUGguaaauu (SEQ ID NO: 883), AGGguauuac (SEQ ID NO: 771), AGUguaugga (SEQ ID NO: 4168), AACguaagau (SEQ ID NO: 4169), GUGguaaggu (SEQ ID NO: 4170), ACUguuagua (SEQ ID NO: 4171), CAGguaucag (SEQ ID NO: 1239), AAGguuaguu (SEQ ID NO: 425), CUGgugagcu (SEQ ID NO: 1754), UUGgugagcu (SEQ ID NO: 4172), UGUguacgua (SEQ ID NO: 4173), GAGgucagcc (SEQ ID NO: 4174), GAGguagaau (SEQ ID NO: 4175), AAGguaugag (SEQ ID NO: 255), UAGguauuuc (SEQ ID NO: 2563), UGUguaacac (SEQ ID NO: 4176), AGUguaaggc (SEQ ID NO: 4177), GAGgucugcu (SEQ ID NO: 4178), AAGguuagca (SEQ ID NO: 418), CAGguaaaug (SEQ ID NO: 1127), AACguaagcu (SEQ ID NO: 4179), CAGgucugca (SEQ ID NO: 4180), CAGguauugu (SEQ ID NO: 1267), GUGguaauuc (SEQ ID NO: 2356), GAGguauaug (SEQ ID NO: 1951), GCCgugagcc (SEQ ID NO: 4181), GAGguaagag (SEQ ID NO: 1883), UGAguaugua (SEQ ID NO: 2787), CAGguaaggg (SEQ ID NO: 1145), GAGguaaauu (SEQ ID NO: 1876), CAGgcaacuu (SEQ ID NO: 4182), UGUguaaguc (SEQ ID NO: 2908), CAGgugcgcu (SEQ ID NO: 4183), CGGguaaacc (SEQ ID NO: 4184), CCGgucaguc (SEQ ID NO: 4185), UAGgugggcg (SEQ ID NO: 4186), GCGgucaguu (SEQ ID NO: 4187), GGGguggguc (SEQ ID NO: 4188), AGCguaauag (SEQ ID NO: 4189), ACGgugaguc (SEQ ID NO: 4190), CUGguacuug (SEQ ID NO: 1722), CAGguuggua (SEQ ID NO: 4191), AGAguaugug (SEQ ID NO: 695), CUGgugggua (SEQ ID NO: 1771), GAGguggcuu (SEQ ID NO: 4192), AUAguauuga (SEQ ID NO: 4193), UGAgucgucc (SEQ ID NO: 4194), CAGgugcucu (SEQ ID NO: 4195), UACguaauau (SEQ ID NO: 4196), GCUguccuga (SEQ ID NO: 4197), CAGgcugcac (SEQ ID NO: 4198), CUGgugcgcu (SEQ ID NO: 1766), GCGguaagaa (SEQ ID NO: 4199), UAAguuacuu (SEQ ID NO: 4200), GAAgugagug (SEQ ID NO: 1840), UAGgcaaguc (SEQ ID NO: 2460), UAAguaaaua (SEQ ID NO: 4201), ACGgugagug (SEQ ID NO: 607), CAGguagguu (SEQ ID NO: 1223), GGGguauaac (SEQ ID NO: 4202), GUUgugaguu (SEQ ID NO: 2410), CAUgugagua (SEQ ID NO: 1539), GAGgugcauu (SEQ ID NO: 4203), AAGguuugua (SEQ ID NO: 466), UCGguaaugu (SEQ ID NO: 4204), CGAguaaggg (SEQ ID NO: 1616), GAGgcacgga (SEQ ID NO: 4205), AGGgugugga (SEQ ID NO: 4206), CAGguauggu (SEQ ID NO: 1257), AAGguagaaa (SEQ ID NO: 203), CAGgugccug (SEQ ID NO: 1373), UGGguauaug (SEQ ID NO: 4207), UGAgugagac (SEQ ID NO: 4208), UGGguaauuu (SEQ ID NO: 2847), AUGguaaaua (SEQ ID NO: 881), AAGgcaaagg (SEQ ID NO: 4209), AGUguuuguu (SEQ ID NO: 4210), AUGguauugg (SEQ ID NO: 4211), CUGgugaggc (SEQ ID NO: 1756), UUGguaaaau (SEQ ID NO: 2948), ACAgugaguu (SEQ ID NO: 563), CAGgugcugu (SEQ ID NO: 4212), GAGguuaaga (SEQ ID NO: 2080), AGAguaagaa (SEQ ID NO: 659), GAGguccgcg (SEQ ID NO: 4213), GUGgugagga (SEQ ID NO: 2382), CAGgugagcc (SEQ ID NO: 1338), CAGgugacau (SEQ ID NO: 1324), AUGgcaagcu (SEQ ID NO: 4214), UCGguaauau (SEQ ID NO: 4215), CAGgcaacaa (SEQ ID NO: 4216), GGGguaggga (SEQ ID NO: 2257), CUGgucucgc (SEQ ID NO: 4217), UAGguaacga (SEQ ID NO: 4218), CGGguaaggu (SEQ ID NO: 4219), UAGguaaugc (SEQ ID NO: 4220), CAGgcaagaa (SEQ ID NO: 1099), ACAguaggua (SEQ ID NO: 4221), CAAguaugag (SEQ ID NO: 1049), GCUguucgaa (SEQ ID NO: 4222), AAGguuaugc (SEQ ID NO: 4223), GAUgugaguu (SEQ ID NO: 2136), CAGguggaga (SEQ ID NO: 1396), AGAguuaguu (SEQ ID NO: 4224), UGAgugugcg (SEQ ID NO: 4225), GAGguacagc (SEQ ID NO: 1907), CAGguaagac (SEQ ID NO: 1139), CAUgugcuuu (SEQ ID NO: 4226), AGGguguguu (SEQ ID NO: 4227), ACAguuaagg (SEQ ID NO: 4228), ACAgugaggg (SEQ ID NO: 4229), GAUguauacc (SEQ ID NO: 4230), UUAguaagcu (SEQ ID NO: 4231), CAGguaagau (SEQ ID NO: 1141), AGAgcugcgu (SEQ ID NO: 4232), GAGgcaaguu (SEQ ID NO: 1860), GAAguaagug (SEQ ID NO: 1819), AAGgugaaaa (SEQ ID NO: 4233), AAGguaccua (SEQ ID NO: 4234), GAGguaucag (SEQ ID NO: 4235), AUGguaugua (SEQ ID NO: 4236), AAGguaugaa (SEQ ID NO: 253), UUGgugagcc (SEQ ID NO: 4237), AAGguuagga (SEQ ID NO: 420), AGGguaugua (SEQ ID NO: 768), CAGguaccga (SEQ ID NO: 4238), AGAguaaacu (SEQ ID NO: 4239), AAGgugcaua (SEQ ID NO: 4240), AAGguaaugu (SEQ ID NO: 167), CCGgugugug (SEQ ID NO: 4241), AGGguaaauu (SEQ ID NO: 729), GGGguuuggc (SEQ ID NO: 4242), CAGguacacg (SEQ ID NO: 1164), UUGguaacca (SEQ ID NO: 4243), GAGgucaggu (SEQ ID NO: 1986), UCUguuggua (SEQ ID NO: 4244), CAGguuaguu (SEQ ID NO: 1458), UUGguauguc (SEQ ID NO: 4245), AAGgugcguc (SEQ ID NO: 4246), AGGguaagaa (SEQ ID NO: 733), UUUguaagcc (SEQ ID NO: 4247), AAGgucaggu (SEQ ID NO: 292), CUGguaaacu (SEQ ID NO: 4248), UCGguaauuu (SEQ ID NO: 4249), CUGguaggcu (SEQ ID NO: 4250), GAGgucugua (SEQ ID NO: 4251), GAGguacuuu (SEQ ID NO: 1922), CUGguaaagg (SEQ ID NO: 4252), CGGgugugug (SEQ ID NO: 1650), CAGguguggu (SEQ ID NO: 4253), UCGguacguc (SEQ ID NO: 4254), CAGgugccag (SEQ ID NO: 4255), GGGgugagaa (SEQ ID NO: 2275), ACAgcuagua (SEQ ID NO: 4256), AAGguauagc (SEQ ID NO: 4257), CUGguaggag (SEQ ID NO: 4258), GCUguacgua (SEQ ID NO: 4259), AAGguaaagg (SEQ ID NO: 128), CAAgcacgag (SEQ ID NO: 4260), CUAguaagac (SEQ ID NO: 4261), CCCguaagcg (SEQ ID NO: 4262), CAAgugugag (SEQ ID NO: 1078), AUGguaaggg (SEQ ID NO: 897), AAGgugaggg (SEQ ID NO: 345), CAAguaggua (SEQ ID NO: 1041), GGUguugcug (SEQ ID NO: 2321), GAGguacugu (SEQ ID NO: 1920), UAGguaagau (SEQ ID NO: 2484), CAGgugcgaa (SEQ ID NO: 1374), GAGguccagg (SEQ ID NO: 4263), UUGguauaca (SEQ ID NO: 2982), GGAgugagua (SEQ ID NO: 2226), GAGgugagau (SEQ ID NO: 2017), AAGguggggc (SEQ ID NO: 4264), CAGguaaacg (SEQ ID NO: 4265), UCGguaacuu (SEQ ID NO: 4266), CAGguaaauu (SEQ ID NO: 1128), GAGgugcgca (SEQ ID NO: 4267), ACUgugagua (SEQ ID NO: 643), ACGgugugac (SEQ ID NO: 4268), GUGguaaguc (SEQ ID NO: 2352), CAGguaggca (SEQ ID NO: 1215), CAGgucagca (SEQ ID NO: 1277), GUGguaugug (SEQ ID NO: 4269), AAAguaucug (SEQ ID NO: 4270), CGGguaugua (SEQ ID NO: 4271), AAGguaauaa (SEQ ID NO: 157), GAGgugggga (SEQ ID NO: 2060), GCUguaggug (SEQ ID NO: 2197), GAAgugaguu (SEQ ID NO: 1841), AAAguauuua (SEQ ID NO: 4272), UAUguaagua (SEQ ID NO: 2653), ACGguaugag (SEQ ID NO: 4273), CUGgugagug (SEQ ID NO: 1761), AGAguaaaau (SEQ ID NO: 4274), GCUguauggc (SEQ ID NO: 4275), AUGguaaacc (SEQ ID NO: 879), GCAguaauaa (SEQ ID NO: 4276), UAAguauuua (SEQ ID NO: 4277), AAUgucagug (SEQ ID NO: 515), AUUgcaggag (SEQ ID NO: 4278), CCGguaagaa (SEQ ID NO: 4279), AAGgcaaguu (SEQ ID NO: 101), GAGguuuguc (SEQ ID NO: 4280), AAGguaacug (SEQ ID NO: 139), AAAguaugag (SEQ ID NO: 4281), GAUguuagua (SEQ ID NO: 4282), CAGguggguc (SEQ ID NO: 1414), AAGguaccga (SEQ ID NO: 4283), CCAguaauua (SEQ ID NO: 4284), GUGguaugcg (SEQ ID NO: 4285), AUGgugcgcu (SEQ ID NO: 4286), CAGgucuaug (SEQ ID NO: 4287), AAGguauuua (SEQ ID NO: 274), CUAguaagau (SEQ ID NO: 4288), AGAguaauuu (SEQ ID NO: 675), GAGguaacgu (SEQ ID NO: 4289), AAGguagcca (SEQ ID NO: 212), CUGgucccgg (SEQ ID NO: 4290), GAGguccuuc (SEQ ID NO: 4291), ACGgucaccc (SEQ ID NO: 4292), AAGguaauac (SEQ ID NO: 158), CAGgugcaug (SEQ ID NO: 1367), AUGguaauag (SEQ ID NO: 4293), UUUguaacac (SEQ ID NO: 4294), UGGguaugau (SEQ ID NO: 4295), CAGgcccccc (SEQ ID NO: 4296), AGAguaguaa (SEQ ID NO: 4297), AGUguaagaa (SEQ ID NO: 814), GAAguauguu (SEQ ID NO: 1833), CAGgugugca (SEQ ID NO: 1434), UUGgugaggg (SEQ ID NO: 3003), UGGguugguu (SEQ ID NO: 4298), CAGguacgua (SEQ ID NO: 1184), GAGgugcggc (SEQ ID NO: 4299), UCUguacggg (SEQ ID NO: 4300), CGGgugcgug (SEQ ID NO: 4301), UACguaagug (SEQ ID NO: 2455), CAUguaagga (SEQ ID NO: 4302), CAGgugacgg (SEQ ID NO: 1329), GAUguaugcu (SEQ ID NO: 4303), UCUgcaauuc (SEQ ID NO: 4304), UGAguaaggc (SEQ ID NO: 2770), GAGguauauu (SEQ ID NO: 1952), AGAgugaguu (SEQ ID NO: 707), AAGguaagcu (SEQ ID NO: 148), UAGgugaagu (SEQ ID NO: 2580), CAGguuagua (SEQ ID NO: 1455), UAUguaagug (SEQ ID NO: 2655), UUGguggggg (SEQ ID NO: 4305), UGAgcucaaa (SEQ ID NO: 4306), UCGguaugua (SEQ ID NO: 4307), UAAguaugcc (SEQ ID NO: 4308), AAUguaagua (SEQ ID NO: 489), CAGguuugca (SEQ ID NO: 4309), ACGgugagag (SEQ ID NO: 4310), CAGguguuuu (SEQ ID NO: 4311), GUGgugagcc (SEQ ID NO: 4312), AGGguacaua (SEQ ID NO: 4313), UAGguaaccc (SEQ ID NO: 4314), GUGgucagua (SEQ ID NO: 4315), CUGgugagcc (SEQ ID NO: 4316), CAGgugcuua (SEQ ID NO: 1390), AUAgucguga (SEQ ID NO: 4317), AUAgugagug (SEQ ID NO: 862), GAGgucaaaa (SEQ ID NO: 4318), CGUguagcuu (SEQ ID NO: 4319), CAGguguuug (SEQ ID NO: 4320), CAGguuggac (SEQ ID NO: 4321), CAGguaagcu (SEQ ID NO: 4322), AGGgucagaa (SEQ ID NO: 4323), CACguauguc (SEQ ID NO: 4324), CACgugagug (SEQ ID NO: 1098), GGGguacgga (SEQ ID NO: 4325), AAGgcaggac (SEQ ID NO: 4326), GAGgugaagc (SEQ ID NO: 4327), GAGguuugaa (SEQ ID NO: 4328), CAGguaagug (SEQ ID NO: 1148), CAGguaacca (SEQ ID NO: 1131), CAGguacucc (SEQ ID NO: 1189), AAGgugcuuu (SEQ ID NO: 371), GAGguaaaua (SEQ ID NO: 1873), GAGgcaggug (SEQ ID NO: 4329), GAGguucgga (SEQ ID NO: 4330), CAGguauuug (SEQ ID NO: 1270), CAGguaaaua (SEQ ID NO: 1125), CAGgugaugu (SEQ ID NO: 1354), CAGgugauac (SEQ ID NO: 4331), GAGgugaggc (SEQ ID NO: 2023), AGGguggggg (SEQ ID NO: 4332), UAAguaaguu (SEQ ID NO: 2425), UGGgugaaca (SEQ ID NO: 4333), UAGguacugc (SEQ ID NO: 4334), CAGgcuccug (SEQ ID NO: 4335), AGGguaggca (SEQ ID NO: 753), CAGgugcccg (SEQ ID NO: 1371), GAGguacauc (SEQ ID NO: 4336), AGGgugugug (SEQ ID NO: 804), AAGguaguaa (SEQ ID NO: 231), UGGguaugag (SEQ ID NO: 2859), GGGgugugug (SEQ ID NO: 2294), CUAguaggug (SEQ ID NO: 4337), GAGgcaagga (SEQ ID NO: 4338), AAGgcaagac (SEQ ID NO: 4339), AAAgugcggu (SEQ ID NO: 4340), AAGguugguu (SEQ ID NO: 450), GAGguuaaug (SEQ ID NO: 4341), UUGgugaguc (SEQ ID NO: 3005), UCGguuagcu (SEQ ID NO: 2738), GCAguaagca (SEQ ID NO: 4342), AAGgcaagca (SEQ ID NO: 4343), ACAguaagcu (SEQ ID NO: 4344), GAGguaacag (SEQ ID NO: 1878), AAAguacgua (SEQ ID NO: 4345), GAGguaauac (SEQ ID NO: 1896), UUGguaggug (SEQ ID NO: 2980), CUGguuaguc (SEQ ID NO: 4346), GAGgugacgc (SEQ ID NO: 4347), ACAguaagga (SEQ ID NO: 4348), AAUguacuua (SEQ ID NO: 4349), GGGguacagu (SEQ ID NO: 4350), CGUguaugug (SEQ ID NO: 4351), UCCguagguu (SEQ ID NO: 4352), GAGguggucg (SEQ ID NO: 4353), UCAgugaguc (SEQ ID NO: 4354), AAAguaagca (SEQ ID NO: 15), GAGgucuggu (SEQ ID NO: 1999), GAGguaauua (SEQ ID NO: 4355), GUAguaagua (SEQ ID NO: 2323), AAGgugggga (SEQ ID NO: 382), UCUgugagca (SEQ ID NO: 4356), GAAguucgug (SEQ ID NO: 4357), ACGgugaggc (SEQ ID NO: 4358), UCAgugagua (SEQ ID NO: 2699), UAGguaguug (SEQ ID NO: 4359), GGUgucuggg (SEQ ID NO: 4360), GGGguaagug (SEQ ID NO: 2252), GAGguggguu (SEQ ID NO: 2066), UGUgugaguu (SEQ ID NO: 4361), CAUguaagua (SEQ ID NO: 1522), AAGguaggug (SEQ ID NO: 229), AAUguaggag (SEQ ID NO: 4362), GAGgcacguc (SEQ ID NO: 4363), CAAguacauu (SEQ ID NO: 4364), UUGguacaga (SEQ ID NO: 4365), GAGguaguag (SEQ ID NO: 1941), AAAgugaggg (SEQ ID NO: 57), UUGgucagug (SEQ ID NO: 4366), AGGgugaguc (SEQ ID NO: 796), CAGgugaaca (SEQ ID NO: 1317), GGUgugggcc (SEQ ID NO: 4367), CGGgugagcu (SEQ ID NO: 4368), GGGgugaguc (SEQ ID NO: 2283), ACAgugagag (SEQ ID NO: 4369), AGGgugaggu (SEQ ID NO: 794), GCUguaaguc (SEQ ID NO: 2194), AUAguagguu (SEQ ID NO: 4370), CAGgcaugug (SEQ ID NO: 1114), AAGguaaguu (SEQ ID NO: 156), CAGguccgug (SEQ ID NO: 4371), GAGgcaggua (SEQ ID NO: 4372), AUGguggaag (SEQ ID NO: 4373), AUGgugggcg (SEQ ID NO: 4374), GAGgugagaa (SEQ ID NO: 2014), AGUgugagca (SEQ ID NO: 832), UUGguaagua (SEQ ID NO: 2962), CAAguaagca (SEQ ID NO: 4375), GGUgugagcu (SEQ ID NO: 2313), CCCgugggua (SEQ ID NO: 4376), CAGguagaau (SEQ ID NO: 4377), CAGgcugagc (SEQ ID NO: 4378), CUGguggccc (SEQ ID NO: 4379), UGAguaagag (SEQ ID NO: 4380), CACguuagcu (SEQ ID NO: 4381), AAGgugaguc (SEQ ID NO: 348), AAGguagcuc (SEQ ID NO: 4382), UCGgugaguu (SEQ ID NO: 4383), GAGgcccuuc (SEQ ID NO: 4384), CAGguuaugc (SEQ ID NO: 4385), CCUguaagcu (SEQ ID NO: 4386), CAGgucuccu (SEQ ID NO: 4387), UAGguaggcu (SEQ ID NO: 4388), GGGguagggg (SEQ ID NO: 4389), AAGguaguga (SEQ ID NO: 4390), GAGguuguug (SEQ ID NO: 4391), CAGguugguu (SEQ ID NO: 1489), AAAguaagcc (SEQ ID NO: 16), ACAgugagug (SEQ ID NO: 562), UGGgugugau (SEQ ID NO: 4392), CCCguaacua (SEQ ID NO: 4393), AAGguguugc (SEQ ID NO: 408), AAAgcuggug (SEQ ID NO: 4394), GAGguauagu (SEQ ID NO: 4395), ACGguaagag (SEQ ID NO: 4396), AUGguacggu (SEQ ID NO: 913), GAGgccaguu (SEQ ID NO: 4397), GAGguaugcg (SEQ ID NO: 1960), UCGgugggag (SEQ ID NO: 4398), AAGguggaua (SEQ ID NO: 372), CCAguguggc (SEQ ID NO: 4399), AGGguaagug (SEQ ID NO: 742), UCUguagguc (SEQ ID NO: 4400), CAGgcaagga (SEQ ID NO: 1102), CGGguaauuu (SEQ ID NO: 1628), AUUgugaguc (SEQ ID NO: 1010), CAGguaaacc (SEQ ID NO: 1121), AAGgucaauu (SEQ ID NO: 4401), AAGgugaaua (SEQ ID NO: 327), GUCguaagaa (SEQ ID NO: 4402), GCGguaaguc (SEQ ID NO: 4403), CUGguagagc (SEQ ID NO: 4404), GAGgucgguc (SEQ ID NO: 4405), CAGguaaaca (SEQ ID NO: 1120), AAGgcaagga (SEQ ID NO: 98), CAGgucgucu (SEQ ID NO: 4406), GGGguagggc (SEQ ID NO: 4407), CUGguacuaa (SEQ ID NO: 1721), GAGguagcug (SEQ ID NO: 1929), CUUgucagcu (SEQ ID NO: 4408), UAGguaaggc (SEQ ID NO: 2489), CUGguauuac (SEQ ID NO: 4409), UAAguacguc (SEQ ID NO: 4410), AAGguaagcc (SEQ ID NO: 146), ACGgugaaag (SEQ ID NO: 4411), CCAgccaaua (SEQ ID NO: 4412), CAGguuuguc (SEQ ID NO: 4413), AAGguauaau (SEQ ID NO: 239), AAGgucuuag (SEQ ID NO: 4414), AGGgugagcu (SEQ ID NO: 791), AAGguuaggg (SEQ ID NO: 4415), CGGguaaauu (SEQ ID NO: 4416), CAGguaacgg (SEQ ID NO: 4417), AGAgugugua (SEQ ID NO: 4418), ACAguaaguu (SEQ ID NO: 549), GAUguaauuu (SEQ ID NO: 4419), GAGguaggga (SEQ ID NO: 1934), UUGgcaagug (SEQ ID NO: 2945), AAAgugagga (SEQ ID NO: 4420), AAGguagugc (SEQ ID NO: 234), AGAguaauuc (SEQ ID NO: 674), GGAguaaaua (SEQ ID NO: 4421), GUGguaccca (SEQ ID NO: 4422), CAGguauugc (SEQ ID NO: 4423), GAUgugaggg (SEQ ID NO: 4424), CAAguaaauc (SEQ ID NO: 1017), CAGgugucuc (SEQ ID NO: 1428), AAGguaacag (SEQ ID NO: 4425), UUGguaaaag (SEQ ID NO: 4426), CAGguaucau (SEQ ID NO: 1240), ACGgugagac (SEQ ID NO: 4427), CUGguaugac (SEQ ID NO: 4428), CAGguucacu (SEQ ID NO: 4429), GAGgugauca (SEQ ID NO: 4430), AGUguaaguc (SEQ ID NO: 4431), AACguaagua (SEQ ID NO: 4432), AAAgugagug (SEQ ID NO: 60), GAGguacagg (SEQ ID NO: 4433), CAAguaauga (SEQ ID NO: 4434), GAUguaagga (SEQ ID NO: 4435), UCAguucccc (SEQ ID NO: 4436), GCGguaagga (SEQ ID NO: 4437), UAGguacuaa (SEQ ID NO: 4438), AAGgugaaag (SEQ ID NO: 321), ACUguaagug (SEQ ID NO: 4439), UGGguaugug (SEQ ID NO: 2862), AUGguaacag (SEQ ID NO: 884), CAGguagggu (SEQ ID NO: 1219), ACAguaagug (SEQ ID NO: 548), AAGgugcucc (SEQ ID NO: 366), AAGgugugcu (SEQ ID NO: 4440), AAGgugguga (SEQ ID NO: 4441), ACGgugcgcc (SEQ ID NO: 4442), AAGguauugc (SEQ ID NO: 4443), GGGguaugug (SEQ ID NO: 2267), CAGgugggcu (SEQ ID NO: 1408), GAGguauguu (SEQ ID NO: 1968), AACgugaaua (SEQ ID NO: 4444), CAGguaaugg (SEQ ID NO: 1154), UAGguaugau (SEQ ID NO: 4445), CAGgcaggug (SEQ ID NO: 1108), GGGguugguc (SEQ ID NO: 4446), AAGguauggg (SEQ ID NO: 262), UAAgugaggc (SEQ ID NO: 4447), CAAgugaucg (SEQ ID NO: 4448), AAAguacggg (SEQ ID NO: 4449), AGAgcuacag (SEQ ID NO: 4450), GAGgugggaa (SEQ ID NO: 2054), CAGguacuuu (SEQ ID NO: 1195), GAGgugagag (SEQ ID NO: 2016), CAGguagguc (SEQ ID NO: 1221), UGGguacagc (SEQ ID NO: 4451), AAGgugucag (SEQ ID NO: 396), AAGgcaagaa (SEQ ID NO: 4452), GAGguaaaca (SEQ ID NO: 4453), AAGguaaagu (SEQ ID NO: 129), AAGguaguca (SEQ ID NO: 4454), CUGguauguc (SEQ ID NO: 4455), GAGguauggg (SEQ ID NO: 1963), AAGguauugu (SEQ ID NO: 273), CUGguacuga (SEQ ID NO: 4456), GAGguaagcu (SEQ ID NO: 1888), UGGgugggua (SEQ ID NO: 2883), CAGguucgug (SEQ ID NO: 4457), AAGguauggu (SEQ ID NO: 4458), CAGgugagca (SEQ ID NO: 1337), UGGguaaauu (SEQ ID NO: 2827), UGUguaggug (SEQ ID NO: 4459), UGUgugagcc (SEQ ID NO: 2921), CUGguaauau (SEQ ID NO: 4460), AAAguauguu (SEQ ID NO: 45), UGUguaagaa (SEQ ID NO: 2903), CUAgugagaa (SEQ ID NO: 4461), AGGguagguc (SEQ ID NO: 757), AAGgugggug (SEQ ID NO: 385), UCGguaagug (SEQ ID NO: 4462), AGUguaaaua (SEQ ID NO: 812), GAUguaagug (SEQ ID NO: 2122), AAGguuagug (SEQ ID NO: 424), UAGguaagca (SEQ ID NO: 2485), CAAgugagaa (SEQ ID NO: 1061), AGUguaagua (SEQ ID NO: 819), CAGgugaauc (SEQ ID NO: 1321), UGGgugagac (SEQ ID NO: 2868), AAGguagggc (SEQ ID NO: 224), CUGguuugug (SEQ ID NO: 1788), GCGguagggc (SEQ ID NO: 4463), GAGguaaucc (SEQ ID NO: 4464), AUUguaauaa (SEQ ID NO: 4465), CUGgugaaua (SEQ ID NO: 1748), AAGguuuaaa (SEQ ID NO: 4466), CCUguacugu (SEQ ID NO: 4467), GCGgugagcg (SEQ ID NO: 4468), AAGguaaucc (SEQ ID NO: 162), UAUgugagua (SEQ ID NO: 2671), CCCgugagug (SEQ ID NO: 1573), CAGgugcaga (SEQ ID NO: 1363), CAGgucaguu (SEQ ID NO: 1284), CAGguaggcu (SEQ ID NO: 4469), AAAguaagug (SEQ ID NO: 23), UAGguugguc (SEQ ID NO: 4470), CAGguugccu (SEQ ID NO: 4471), AAGguaugga (SEQ ID NO: 260), GGUguggacg (SEQ ID NO: 4472), AAAgugagaa (SEQ ID NO: 51), AGGgugagag (SEQ ID NO: 788), GAUguggcau (SEQ ID NO: 4473), UCGguaaggu (SEQ ID NO: 4474), GAGgugcguc (SEQ ID NO: 4475), CGGgugaguc (SEQ ID NO: 4476), AAGguacggg (SEQ ID NO: 190), GAGguucuug (SEQ ID NO: 4477), AAGgugcuug (SEQ ID NO: 4478), UAGguaugua (SEQ ID NO: 2551), AUGgucagca (SEQ ID NO: 4479), CGGguacuca (SEQ ID NO: 4480), AGGgugagga (SEQ ID NO: 792), AUCgugagua (SEQ ID NO: 869), UCAguaagua (SEQ ID NO: 2689), UAGguaaaua (SEQ ID NO: 2469), AAGguaauug (SEQ ID NO: 170), GAAgucagug (SEQ ID NO: 1835), CAGguacaaa (SEQ ID NO: 1160), AAAguuaauc (SEQ ID NO: 4481), AGCgugagcg (SEQ ID NO: 4482), CCGgcuggug (SEQ ID NO: 4483), AGUguaauuu (SEQ ID NO: 4484), UGAgccacuc (SEQ ID NO: 4485), GGGgucugua (SEQ ID NO: 4486), AUGgcauguc (SEQ ID NO: 4487), CGGguaaaga (SEQ ID NO: 4488), AGGguagcau (SEQ ID NO: 4489), CGGguaggag (SEQ ID NO: 1631), GAGguucgug (SEQ ID NO: 4490), UAAguuauuc (SEQ ID NO: 4491), UAUguaagau (SEQ ID NO: 2650), AAGguaguuu (SEQ ID NO: 237), CAGgugguau (SEQ ID NO: 4492), GUGguaauga (SEQ ID NO: 2355), AAGgugauuu (SEQ ID NO: 359), CAGgugaagu (SEQ ID NO: 4493), GUAguaauua (SEQ ID NO: 4494), AUGguuggug (SEQ ID NO: 4495), CCAguaagug (SEQ ID NO: 1557), UAGgugagag (SEQ ID NO: 2589), AUGgugaggc (SEQ ID NO: 959), AAAguuagug (SEQ ID NO: 72), AAGgugccuu (SEQ ID NO: 4496), UAGguaugag (SEQ ID NO: 2546), CAGgugugac (SEQ ID NO: 1431), CUGguggguu (SEQ ID NO: 1774), AUGguaagga (SEQ ID NO: 896), UCUguaagaa (SEQ ID NO: 2740), UCCgugaguu (SEQ ID NO: 4497), AAAgcaggua (SEQ ID NO: 4498), UAUgugagug (SEQ ID NO: 2672), CAGguggagg (SEQ ID NO: 4499), CAGguuagac (SEQ ID NO: 4500), AUAguaagac (SEQ ID NO: 846), AAGguguugu (SEQ ID NO: 4501), GAGgucugug (SEQ ID NO: 4502), AAGguaagau (SEQ ID NO: 144), CAUguaaguu (SEQ ID NO: 1524), CUGguaauua (SEQ ID NO: 4503), CAGguaggcg (SEQ ID NO: 4504), AGAguaaguc (SEQ ID NO: 669), UGGgugagga (SEQ ID NO: 2872), AAUguaggua (SEQ ID NO: 4505), UAGguuagca (SEQ ID NO: 4506), GGGguaggua (SEQ ID NO: 2258), GAGguauugc (SEQ ID NO: 4507), AUUguacaca (SEQ ID NO: 4508), GAAguaggua (SEQ ID NO: 4509), GGAguaagcu (SEQ ID NO: 2212), UAGguaugug (SEQ ID NO: 2553), GAGgugaaua (SEQ ID NO: 2007), GAGgugggau (SEQ ID NO: 2056), AAGguaaucu (SEQ ID NO: 163), GGUgugaguu (SEQ ID NO: 4510), AACgugaguu (SEQ ID NO: 4511), GAGguaaccg (SEQ ID NO: 4512), UAGguaagga (SEQ ID NO: 2488), AUUguaagaa (SEQ ID NO: 4513), UGGgugagca (SEQ ID NO: 2870), AAGguaaggc (SEQ ID NO: 150), CCAguaucgu (SEQ ID NO: 4514), CCGgugggug (SEQ ID NO: 4515), GAGguagugu (SEQ ID NO: 4516), ACGgugggaa (SEQ ID NO: 4517), GAGgugaccu (SEQ ID NO: 2011), CACguaugua (SEQ ID NO: 4518), AGGgugggga (SEQ ID NO: 799), AAUguaaguc (SEQ ID NO: 490), AAAguuaagu (SEQ ID NO: 70), CAUgugagug (SEQ ID NO: 1541), AGAguauguc (SEQ ID NO: 694), GCGguaugac (SEQ ID NO: 4519), CGGgugaguu (SEQ ID NO: 1643), CCGguauuuu (SEQ ID NO: 4520), GAGguagaac (SEQ ID NO: 4521), UAGguaugaa (SEQ ID NO: 2545), CAGgcgcgug (SEQ ID NO: 4522), CAAguaaguc (SEQ ID NO: 1027), AGUguaagau (SEQ ID NO: 816), AAGguucuac (SEQ ID NO: 4523), CCAguaagua (SEQ ID NO: 1555), GAGguagcag (SEQ ID NO: 4524), CAGgucuguu (SEQ ID NO: 1312), CAGguacaau (SEQ ID NO: 1162), CCGguaaaga (SEQ ID NO: 1574), UAAgugcugu (SEQ ID NO: 4525), AGGgugagaa (SEQ ID NO: 786), CUCguaaggu (SEQ ID NO: 4526), CAGgucagcu (SEQ ID NO: 4527), CAGguaaggc (SEQ ID NO: 1144), AGGgugcagg (SEQ ID NO: 4528), GAGgugaaac (SEQ ID NO: 4529), AGGguaagua (SEQ ID NO: 740), AAUguaugcc (SEQ ID NO: 4530), AAGguaagca (SEQ ID NO: 145), ACGguacggu (SEQ ID NO: 587), AAGguaauga (SEQ ID NO: 164), UCUgcucaau (SEQ ID NO: 4531), ACGguaaugu (SEQ ID NO: 4532), AAGguaguug (SEQ ID NO: 4533), ACGguaagug (SEQ ID NO: 580), CAGgugauga (SEQ ID NO: 4534), GAGguaacac (SEQ ID NO: 4535), GAGguaggua (SEQ ID NO: 1937), CAGguaccuu (SEQ ID NO: 1179), CAGguaauaa (SEQ ID NO: 1150), UUGgugggug (SEQ ID NO: 3016), CUGguaauga (SEQ ID NO: 1710), UAGguaaguc (SEQ ID NO: 2492), AGGgugugac (SEQ ID NO: 4536), GAGgcaauaa (SEQ ID NO: 4537), GUGguaaagc (SEQ ID NO: 4538), CUGgugggcg (SEQ ID NO: 4539), GAUguauguu (SEQ ID NO: 2128), AGGgugagac (SEQ ID NO: 787), UCGgucagca (SEQ ID NO: 4540), AUGgugauua (SEQ ID NO: 4541), CGAgugugua (SEQ ID NO: 4542), CAGguuggug (SEQ ID NO: 1488), AGCgcaagua (SEQ ID NO: 4543), UGGguacguu (SEQ ID NO: 4544), GAGguauuug (SEQ ID NO: 1974), AGUguacaua (SEQ ID NO: 4545), AUGguaagua (SEQ ID NO: 898), ACAguagguu (SEQ ID NO: 4546), AAGgugagag (SEQ ID NO: 337), UUGgugaagu (SEQ ID NO: 4547), AAAguaugua (SEQ ID NO: 43), UGGguaagga (SEQ ID NO: 4548), UAGgugccuu (SEQ ID NO: 4549), and CCUgugggug (SEQ ID NO: 4550). Additional exemplary gene sequences and splice site sequences (e.g., 5’ splice site sequences) include UCCguaaguu (SEQ ID NO: 4551), GUGguaaacg (SEQ ID NO: 4552), CGGgugcggu (SEQ ID NO: 4553), CAUguacuuc (SEQ ID NO: 4554), AGAguaaagg (SEQ ID NO: 4555), CGCgugagua (SEQ ID NO: 4556), AGAgugggca (SEQ ID NO: 4557), AGAguaagcc (SEQ ID NO: 4558), AGAguaaaca (SEQ ID NO: 4559), GUGguuauga (SEQ ID NO: 4560), AGGguaauaa (SEQ ID NO: 4561), UGAguaagac (SEQ ID NO: 4562), AGAguuuguu (SEQ ID NO: 4563), CGGgucugca (SEQ ID NO: 4564), CAGguaaguc (SEQ ID NO: 4565), AAGguagaau (SEQ ID NO: 4566), CAGgucccuc (SEQ ID NO: 4567), AGAguaaugg (SEQ ID NO: 4568), GAGgucuaag (SEQ ID NO: 4569), AGAguagagu (SEQ ID NO: 4570), AUGgucagua (SEQ ID NO: 4571), GAGgccuggg (SEQ ID NO: 4572), AAGguguggc (SEQ ID NO: 4573), AGAgugaucu (SEQ ID NO: 4574), AAGguaucca (SEQ ID NO: 4575), UUCguaagua (SEQ ID NO: 4576), UAAgugggug (SEQ ID NO: 4577), GCCgugaacg (SEQ ID NO: 4578), GAGguugugg (SEQ ID NO: 4579), UAUguaugca (SEQ ID NO: 4580), UGUguaacaa (SEQ ID NO: 4581), AGGguauuag (SEQ ID NO: 4582), UGAguauauc (SEQ ID NO: 4583), AGAguuugug (SEQ ID NO: 4584), GAGgucgcug (SEQ ID NO: 4585), GAGgucaucg (SEQ ID NO: 4586), ACGguaaagc (SEQ ID NO: 4587), UGAguacuug (SEQ ID NO: 4588), CGAgucgccg (SEQ ID NO: 4589), CUGguacguc (SEQ ID NO: 4590), AGGguauugc (SEQ ID NO: 4591), GAAgugaaug (SEQ ID NO: 4592), CAGaugaguc (SEQ ID NO: 4593), UGGguauugg (SEQ ID NO: 4594), UGAguaaaga (SEQ ID NO: 4595), GUGguuccug (SEQ ID NO: 4596), UGAgcaagua (SEQ ID NO: 4597), UAUguaagag (SEQ ID NO: 4598), AAGgucuugc (SEQ ID NO: 4599), AAAgcaugug (SEQ ID NO: 4600), AGAguacagu (SEQ ID NO: 4601), GUGguaaucc (SEQ ID NO: 4602), CAGguagagg (SEQ ID NO: 4603), AAGguacaac (SEQ ID NO: 4604), UGGgcagcau (SEQ ID NO: 4605), CCGgucauca (SEQ ID NO: 4606), CCGguuugua (SEQ ID NO: 4607), UGAguaaggg (SEQ ID NO: 4608), GAAguaugua (SEQ ID NO: 4609), GGGguagcuc (SEQ ID NO: 4610), GCUguacaua (SEQ ID NO: 4611), CUGgucucuu (SEQ ID NO: 4612), GUGguaaaug (SEQ ID NO: 4613), AUCguaagug (SEQ ID NO: 4614), GAGgcaugua (SEQ ID NO: 4615), AAGgucuccc (SEQ ID NO: 4616), UGGgugcguu (SEQ ID NO: 4617), UGUguagguu (SEQ ID NO: 4618), GAAgugagca (SEQ ID NO: 4619), GGUguaauuu (SEQ ID NO: 4620), CUGgugaaau (SEQ ID NO: 4621), AUCguaaguc (SEQ ID NO: 4622), AGAguaaucc (SEQ ID NO: 4623), GGAguagguc (SEQ ID NO: 4624), GAGguaccaa (SEQ ID NO: 4625), CUUguaggug (SEQ ID NO: 4626), AAGguauaag (SEQ ID NO: 4627), AGAguuggua (SEQ ID NO: 4628), AUGguuugug (SEQ ID NO: 4629), UGGgucagau (SEQ ID NO: 4630), AGAguaggac (SEQ ID NO: 4631), AGAguagugu (SEQ ID NO: 4632), AGAguaggag (SEQ ID NO: 4633), CAGgucucua (SEQ ID NO: 4634), AAGguggaug (SEQ ID NO: 4635), UGGguaucaa (SEQ ID NO: 4636), GAUguaugga (SEQ ID NO: 4637), AAGguguuuc (SEQ ID NO: 4638), GCAguguaaa (SEQ ID NO: 4639), UUAguaugua (SEQ ID NO: 4640), UCUguaugca (SEQ ID NO: 4641), AAUguaaaau (SEQ ID NO: 4642), AGAguaaauu (SEQ ID NO: 4643), GGGguacuuu (SEQ ID NO: 4644), GAAguuugau (SEQ ID NO: 4645), AAAguagauu (SEQ ID NO: 4646), UGUguagagu (SEQ ID NO: 4647), UGGguaagcg (SEQ ID NO: 4648), CGGguucagg (SEQ ID NO: 4649), AGGguacgac (SEQ ID NO: 4650), UCGguaagaa (SEQ ID NO: 4651), AGGguuggca (SEQ ID NO: 4652), AAAguacagu (SEQ ID NO: 4653), UAAguuaagg (SEQ ID NO: 4654), AUGguaaugu (SEQ ID NO: 4655), GUGguuuuac (SEQ ID NO: 4656), AGAguaacaa (SEQ ID NO: 4657), AAGguagccc (SEQ ID NO: 4658), GCGgugaggc (SEQ ID NO: 4659), AUGguucagc (SEQ ID NO: 4660), AAGguacuua (SEQ ID NO: 4661), AAGguccgug (SEQ ID NO: 4662), UAGguaagcg (SEQ ID NO: 4663), AUGguaccuu (SEQ ID NO: 4664), GCCguggugg (SEQ ID NO: 4665), CUGgugcguc (SEQ ID NO: 4666), CAGguggaaa (SEQ ID NO: 4667), AAAgucugua (SEQ ID NO: 4668), GAGguaaccc (SEQ ID NO: 4669), AGAguauggg (SEQ ID NO: 4670), UAUgccccug (SEQ ID NO: 4671), AAGgugccag (SEQ ID NO: 4672), ACGgugcggc (SEQ ID NO: 4673), AGGguacuga (SEQ ID NO: 4674), AGAguaagcg (SEQ ID NO: 4675), CUGgcaaggg (SEQ ID NO: 4676), CCAgugugug (SEQ ID NO: 4677), GAGguagacg (SEQ ID NO: 4678), CGGgugcggg (SEQ ID NO: 4679), GAUguaagcu (SEQ ID NO: 4680), AUUguauuua (SEQ ID NO: 4681), UGCgugagug (SEQ ID NO: 4682), CUGgucuaua (SEQ ID NO: 4683), GAGgugcuag (SEQ ID NO: 4684), GAGgugccau (SEQ ID NO: 4685), CAGguacguc (SEQ ID NO: 4686), GAGguucagc (SEQ ID NO: 4687), AACguaagaa (SEQ ID NO: 4688), AGAguaguac (SEQ ID NO: 4689), AAGguaacgg (SEQ ID NO: 4690), UAGgugugac (SEQ ID NO: 4691), CCGguaauag (SEQ ID NO: 4692), CAGguaccag (SEQ ID NO: 4693), UUUguaauug (SEQ ID NO: 4694), AAUguacgaa (SEQ ID NO: 4695), CAGguaauga (SEQ ID NO: 4696), AUCgucaagg (SEQ ID NO: 4697), CUGguagaug (SEQ ID NO: 4698), GGGgugcagu (SEQ ID NO: 4699), AGUgugagaa (SEQ ID NO: 4700), GGGguuuuau (SEQ ID NO: 4701), CCUguccccu (SEQ ID NO: 4702), AUUgugaagu (SEQ ID NO: 4703), AAGguaaacg (SEQ ID NO: 4704), UACgucgugg (SEQ ID NO: 4705), AAGgugccau (SEQ ID NO: 4706), GGGgucccag (SEQ ID NO: 4707), UAUguauggu (SEQ ID NO: 4708), CGGguaauua (SEQ ID NO: 4709), CGGguacucc (SEQ ID NO: 4710), CAGgugacuu (SEQ ID NO: 4711), AGUguggguu (SEQ ID NO: 4712), AGAguauggc (SEQ ID NO: 4713), AAGgccaaca (SEQ ID NO: 4714), AAAgcaagua (SEQ ID NO: 4715), UCAguagguc (SEQ ID NO: 4716), GUGguggcgg (SEQ ID NO: 4717), CAUguauccu (SEQ ID NO: 4718), UCGgugagcc (SEQ ID NO: 4719), AUAguugggu (SEQ ID NO: 4720), AAUguuagcu (SEQ ID NO: 4721), AUGgugaaug (SEQ ID NO: 4722), CGGguaaugu (SEQ ID NO: 4723), UCUguaggug (SEQ ID NO: 4724), CCGgugaggc (SEQ ID NO: 4725), UGAguccacu (SEQ ID NO: 4726), CUAguaagag (SEQ ID NO: 4727), CGGguggggc (SEQ ID NO: 4728), CGAguaagca (SEQ ID NO: 4729), UGUgccaauu (SEQ ID NO: 4730), UCGguaagcc (SEQ ID NO: 4731), UAUguaggug (SEQ ID NO: 4732), UUGgugggcc (SEQ ID NO: 4733), GAGgcugggc (SEQ ID NO: 4734), AGAguaacuu (SEQ ID NO: 4735), ACGguagguc (SEQ ID NO: 4736), CAGgcccaga (SEQ ID NO: 4737), CCGguggguu (SEQ ID NO: 4738), AAGgugacgg (SEQ ID NO: 4739), GGGguacagc (SEQ ID NO: 4740), CAUguaaguc (SEQ ID NO: 4741), AUUgugagaa (SEQ ID NO: 4742), UGUguaagga (SEQ ID NO: 4743), UUUguaagau (SEQ ID NO: 4744), AGGgucauuu (SEQ ID NO: 4745), UGGguuuguu (SEQ ID NO: 4746), CGAguaagcc (SEQ ID NO: 4747), GUGgugugua (SEQ ID NO: 4748), AUGguauaac (SEQ ID NO: 4749), UGGguacgua (SEQ ID NO: 4750), AAAguagagu (SEQ ID NO: 4751), UCGguaacug (SEQ ID NO: 4752), AGAguaauga (SEQ ID NO: 4753), AUGguggguc (SEQ ID NO: 4754), AGAguaauau (SEQ ID NO: 4755), CAGguacugg (SEQ ID NO: 4756), UAAgucaguu (SEQ ID NO: 4757), GCGguagaga (SEQ ID NO: 4758), AAGgugaugg (SEQ ID NO: 4759), ACAguauguu (SEQ ID NO: 4760), GAUguacguc (SEQ ID NO: 4761), UAGguuucuc (SEQ ID NO: 4762), GAGgcauggg (SEQ ID NO: 4763), AUAgcuaagu (SEQ ID NO: 4764), GUAgucugua (SEQ ID NO: 4765), AAGgugaacg (SEQ ID NO: 4766), GUGguggucg (SEQ ID NO: 4767), GAGguugauc (SEQ ID NO: 4768), UGAguggguu (SEQ ID NO: 4769), ACUguacgug (SEQ ID NO: 4770), CUGgugacug (SEQ ID NO: 4771), CAAguuaagc (SEQ ID NO: 4772), GAGguaccca (SEQ ID NO: 4773), AACguaacuu (SEQ ID NO: 4774), CAGguuacua (SEQ ID NO: 4775), AGAguuaguc (SEQ ID NO: 4776), UGGgcacguc (SEQ ID NO: 4777), AGUguauggu (SEQ ID NO: 4778), AAGguugcaa (SEQ ID NO: 4779), CAGguuguua (SEQ ID NO: 4780), AAGgcauccc (SEQ ID NO: 4781), GAUguaaggc (SEQ ID NO: 4782), AGGguacggg (SEQ ID NO: 4783), GAGgucaaag (SEQ ID NO: 4784), CAAgugagcg (SEQ ID NO: 4785), AGAguaaucu (SEQ ID NO: 4786), UCGguagcug (SEQ ID NO: 4787), AAAguaguag (SEQ ID NO: 4788), CAGguucguc (SEQ ID NO: 4789), CGUguaugaa (SEQ ID NO: 4790), AGUguaaaaa (SEQ ID NO: 4791), AAGgucucac (SEQ ID NO: 4792), UAGguggagc (SEQ ID NO: 4793), UGAguaggug (SEQ ID NO: 4794), AGAguaugcc (SEQ ID NO: 4795), GAGguugcau (SEQ ID NO: 4796), CAAguaagag (SEQ ID NO: 4797), UCUgugugcc (SEQ ID NO: 4798), GAGgugaugc (SEQ ID NO: 4799), GGGgugauaa (SEQ ID NO: 4800), CCCgugagcc (SEQ ID NO: 4801), AGAguaacug (SEQ ID NO: 4802), GCGguaagua (SEQ ID NO: 4803), AGAguacauc (SEQ ID NO: 4804), UCGgucuggg (SEQ ID NO: 4805), UAAguaucuc (SEQ ID NO: 4806), GGCguagguu (SEQ ID NO: 4807), AGAguacgcc (SEQ ID NO: 4808), GAUgucuucu (SEQ ID NO: 4809), AGGgcaaggu (SEQ ID NO: 4810), CGAguaugau (SEQ ID NO: 4811), AUGguagagu (SEQ ID NO: 4812), CAAguacgag (SEQ ID NO: 4813), UCGguaugau (SEQ ID NO: 4814), CCGguguguu (SEQ ID NO: 4815), AGGgucugug (SEQ ID NO: 4816), GGAguaggcu (SEQ ID NO: 4817), AAGgucuaug (SEQ ID NO: 4818), GCAgugcgug (SEQ ID NO: 4819), UGGgugagaa (SEQ ID NO: 4820), AGGguaaagu (SEQ ID NO: 4821), GAGguaggac (SEQ ID NO: 4822), CUAguaagca (SEQ ID NO: 4823), UUAguaggcu (SEQ ID NO: 4824), CUGgugggau (SEQ ID NO: 4825), CUGguuagua (SEQ ID NO: 4826), AAGguacgug (SEQ ID NO: 4827), CGGgugagau (SEQ ID NO: 4828), AAGgugcaug (SEQ ID NO: 4829), AAUgugggcu (SEQ ID NO: 4830), CAGguugacu (SEQ ID NO: 4831), CAGguuacag (SEQ ID NO: 4832), GCGguaacau (SEQ ID NO: 4833), AUUgucaguc (SEQ ID NO: 4834), CAAguauaca (SEQ ID NO: 4835), GAUguccgcc (SEQ ID NO: 4836), AAGgugcgga (SEQ ID NO: 4837), AACguaagag (SEQ ID NO: 4838), UGGguuggua (SEQ ID NO: 4839), CAAguguaag (SEQ ID NO: 4840), GUGguaacgu (SEQ ID NO: 4841), CUGgugauca (SEQ ID NO: 4842), AGGguggggc (SEQ ID NO: 4843), UCGguaaaga (SEQ ID NO: 4844), CAGguacacc (SEQ ID NO: 4845), CGGguaaggg (SEQ ID NO: 4846), CAAguuugcu (SEQ ID NO: 4847), ACAgugcgug (SEQ ID NO: 4848), UUGguauggg (SEQ ID NO: 4849), GAGgcucauc (SEQ ID NO: 4850), CUGguaauag (SEQ ID NO: 4851), AUGguggaua (SEQ ID NO: 4852), UCAgugaauu (SEQ ID NO: 4853), AAUguaauua (SEQ ID NO: 4854), GCAgucuaaa (SEQ ID NO: 4855), AAGguauucu (SEQ ID NO: 4856), GAGgucauca (SEQ ID NO: 4857), UGGguccaug (SEQ ID NO: 4858), AGAguuugua (SEQ ID NO: 4859), AGGguagacu (SEQ ID NO: 4860), AAGguaggac (SEQ ID NO: 4861), UGUguguuga (SEQ ID NO: 4862), UCAguacgug (SEQ ID NO: 4863), AUGgucucuc (SEQ ID NO: 4864), UGAguuagua (SEQ ID NO: 4865), UGAguaaagu (SEQ ID NO: 4866), GAGgugaccg (SEQ ID NO: 4867), GAGguauauc (SEQ ID NO: 4868), CAGgugccau (SEQ ID NO: 4869), AGAgugguga (SEQ ID NO: 4870), GUUguaagaa (SEQ ID NO: 4871), AGAguaaaua (SEQ ID NO: 4872), AGGgugaagg (SEQ ID NO: 4873), CUGguagauu (SEQ ID NO: 4874), GAGguucagg (SEQ ID NO: 4875), AGGgucuuca (SEQ ID NO: 4876), CUGguaaccu (SEQ ID NO: 4877), ACAguacuga (SEQ ID NO: 4878), AGAguggguc (SEQ ID NO: 4879), AUGguaugag (SEQ ID NO: 4880), AAGguuauau (SEQ ID NO: 4881), AGAguauagu (SEQ ID NO: 4882), AAAguaugaa (SEQ ID NO: 4883), UAGguggcua (SEQ ID NO: 4884), ACCguauggg (SEQ ID NO: 4885), AAAguauaau (SEQ ID NO: 4886), UUUguauggc (SEQ ID NO: 4887), GGGgucgcgu (SEQ ID NO: 4888), GUGgugguuu (SEQ ID NO: 4889), CAGguuugac (SEQ ID NO: 4890), GGAguaggcg (SEQ ID NO: 4891), GAGguacccu (SEQ ID NO: 4892), AUGgugugca (SEQ ID NO: 4893), GUGguuggug (SEQ ID NO: 4894), AAAguaugcu (SEQ ID NO: 4895), UAAguuacau (SEQ ID NO: 4896), ACAguaugag (SEQ ID NO: 4897), GGAguauguu (SEQ ID NO: 4898), UUUgugagaa (SEQ ID NO: 4899), AAUgugcguu (SEQ ID NO: 4900), CAGguagagu (SEQ ID NO: 4901), AUGguguuaa (SEQ ID NO: 4902), CAUgugcguc (SEQ ID NO: 4903), AUAguuggau (SEQ ID NO: 4904), GAGguacgua (SEQ ID NO: 4905), GUUgugagaa (SEQ ID NO: 4906), CAAguacauc (SEQ ID NO: 4907), GAGguaguuu (SEQ ID NO: 4908), ACUguacaga (SEQ ID NO: 4909), CCGguuguga (SEQ ID NO: 4910), UGGgucagug (SEQ ID NO: 4911), GUAguaagaa (SEQ ID NO: 4912), GACguacuuu (SEQ ID NO: 4913), AGAgucaguc (SEQ ID NO: 4914), UAGguuaguu (SEQ ID NO: 4915), AGGgcagcag (SEQ ID NO: 4916), AAGguccuac (SEQ ID NO: 4917), AAUguaauug (SEQ ID NO: 4918), CAGgugcggg (SEQ ID NO: 4919), CUGguaaugg (SEQ ID NO: 4920), CAAguagccc (SEQ ID NO: 4921), GAAgucaguu (SEQ ID NO: 4922), ACAguaauug (SEQ ID NO: 4923), UUAguuagua (SEQ ID NO: 4924), CCUguauuuu (SEQ ID NO: 4925), AUCguaagaa (SEQ ID NO: 4926), CCAgugagca (SEQ ID NO: 4927), GAAguaaggc (SEQ ID NO: 4928), UGAgugggua (SEQ ID NO: 4929), UCAgugguag (SEQ ID NO: 4930), UCUguacagg (SEQ ID NO: 4931), CGAgugagug (SEQ ID NO: 4932), UCCguaugug (SEQ ID NO: 4933), CAUgccguuu (SEQ ID NO: 4934), AAAgugacuu (SEQ ID NO: 4935), AGAguaggca (SEQ ID NO: 4936), GAAguaagag (SEQ ID NO: 4937), CAGgcagguu (SEQ ID NO: 4938), UUGguagagc (SEQ ID NO: 4939), AAGguggaaa (SEQ ID NO: 4940), GAGgcagguc (SEQ ID NO: 4941), AUGguacgac (SEQ ID NO: 4942), AGGguaggaa (SEQ ID NO: 4943), AGGguaggua (SEQ ID NO: 4944), UUGguaaggu (SEQ ID NO: 4945), AUGguacaga (SEQ ID NO: 4946), CAGguagagc (SEQ ID NO: 4947), UAGguaaggu (SEQ ID NO: 4948), GGGguuagag (SEQ ID NO: 4949), AAGguaucaa (SEQ ID NO: 4950), GAGguagccc (SEQ ID NO: 4951), CAGgugccuc (SEQ ID NO: 4952), GCAguaagag (SEQ ID NO: 4953), ACGguagagu (SEQ ID NO: 4954), UGGguaaugg (SEQ ID NO: 4955), CUGgucaguu (SEQ ID NO: 4956), GUGguacauu (SEQ ID NO: 4957), AAAguagguu (SEQ ID NO: 4958), AAGgccaaga (SEQ ID NO: 4959), CGGgugggca (SEQ ID NO: 4960), ACGguccggg (SEQ ID NO: 4961), CGAguaugag (SEQ ID NO: 4962), CUGguaugcc (SEQ ID NO: 4963), GAGguggaug (SEQ ID NO: 4964), CAGgccuuuc (SEQ ID NO: 4965), AAAguacauc (SEQ ID NO: 4966), AAAguaauca (SEQ ID NO: 4967), GAGguaacug (SEQ ID NO: 4968), CUGguaaaga (SEQ ID NO: 4969), CGUguaagca (SEQ ID NO: 4970), UGGgcaagua (SEQ ID NO: 4971), GCGguggcga (SEQ ID NO: 4972), GAGguggccg (SEQ ID NO: 4973), AUUgcaugca (SEQ ID NO: 4974), ACGgugacug (SEQ ID NO: 4975), CAGgucagau (SEQ ID NO: 4976), AGAguaacuc (SEQ ID NO: 4977), UGAguaacag (SEQ ID NO: 4978), AAGguacccg (SEQ ID NO: 4979), AGGguaggcu (SEQ ID NO: 4980), GGGgcaggac (SEQ ID NO: 4981), CCUguaagug (SEQ ID NO: 4982), AUUguaagug (SEQ ID NO: 4983), ACUguacgag (SEQ ID NO: 4984), GUAguagugu (SEQ ID NO: 4985), AGAguaugag (SEQ ID NO: 4986), UCAguguggg (SEQ ID NO: 4987), UGGguauaua (SEQ ID NO: 4988), UAGguagcua (SEQ ID NO: 4989), GGGguaaaga (SEQ ID NO: 4990), AGGguuacuu (SEQ ID NO: 4991), CAUguaaaug (SEQ ID NO: 4992), GGAguaguaa (SEQ ID NO: 4993), CAGgucaauc (SEQ ID NO: 4994), CGGguuagug (SEQ ID NO: 4995), UAGguacaug (SEQ ID NO: 4996), UAGguuaaga (SEQ ID NO: 4997), UGGguaccuu (SEQ ID NO: 4998), CGGguggaca (SEQ ID NO: 4999), CAGgucuuac (SEQ ID NO: 5000), AAGguggagc (SEQ ID NO: 5001), AUGguaacca (SEQ ID NO: 5002), UCGguaaguu (SEQ ID NO: 5003), UAUguacaaa (SEQ ID NO: 5004), AAUguagauu (SEQ ID NO: 5005), GUAgcuagua (SEQ ID NO: 5006), AAGguauugg (SEQ ID NO: 5007), GAGgucuuug (SEQ ID NO: 5008), GAAguucagg (SEQ ID NO: 5009), UGGguaucac (SEQ ID NO: 5010), AGAguacugg (SEQ ID NO: 5011), CAGguuaaug (SEQ ID NO: 5012), AGGguacgug (SEQ ID NO: 5013), AGGgcacagg (SEQ ID NO: 5014), CUGguuaguu (SEQ ID NO: 5015), UUGguacgag (SEQ ID NO: 5016), ACGgugauca (SEQ ID NO: 5017), CCUgugagag (SEQ ID NO: 5018), GAGgugaagu (SEQ ID NO: 5019), AAGguacauc (SEQ ID NO: 5020), UCUguaugug (SEQ ID NO: 5021), UUGguggaag (SEQ ID NO: 5022), UGGgcagguu (SEQ ID NO: 5023), GAAguggagc (SEQ ID NO: 5024), ACAguaagac (SEQ ID NO: 5025), CGGguaccaa (SEQ ID NO: 5026), CAAguacguc (SEQ ID NO: 5027), AGAgugaggg (SEQ ID NO: 5028), CGGguaagaa (SEQ ID NO: 5029), AAUguaggug (SEQ ID NO: 5030), AUCgugugcu (SEQ ID NO: 5031), UAGgucaugg (SEQ ID NO: 5032), CAGguuuuga (SEQ ID NO: 5033), AAGgcaugca (SEQ ID NO: 5034), GAGgugcugc (SEQ ID NO: 5035), AAGguuaaua (SEQ ID NO: 5036), CAGguucauc (SEQ ID NO: 5037), GCGguaggug (SEQ ID NO: 5038), GACgugagua (SEQ ID NO: 5039), CAGgucuacu (SEQ ID NO: 5040), UUGguaugag (SEQ ID NO: 5041), AGCgugggca (SEQ ID NO: 5042), AUGguaaggu (SEQ ID NO: 5043), AUGguaccuc (SEQ ID NO: 5044), UUGguauggu (SEQ ID NO: 5045), UAUguaugaa (SEQ ID NO: 5046), UGGguauggg (SEQ ID NO: 5047), GAUguaaaua (SEQ ID NO: 5048), CCGguaaguu (SEQ ID NO: 5049), GAGgucugaa (SEQ ID NO: 5050), GAGgugcgag (SEQ ID NO: 5051), CUGgucagcc (SEQ ID NO: 5052), CAGguuuugu (SEQ ID NO: 5053), CGGguggugu (SEQ ID NO: 5054), UAAguuagua (SEQ ID NO: 5055), UUUgugugug (SEQ ID NO: 5056), CAGguuaacc (SEQ ID NO: 5057), UUGguacuuu (SEQ ID NO: 5058), GCUguaaggc (SEQ ID NO: 5059), AGGguggcug (SEQ ID NO: 5060), GAUguaaaaa (SEQ ID NO: 5061), AAGgucaaaa (SEQ ID NO: 5062), CAGguagcgc (SEQ ID NO: 5063), CAGguuuggc (SEQ ID NO: 5064), GAGgugguuu (SEQ ID NO: 5065), CGGguaaaua (SEQ ID NO: 5066), CUGguucggu (SEQ ID NO: 5067), GGAgugagcc (SEQ ID NO: 5068), AAGgugcgcg (SEQ ID NO: 5069), GAAguacauc (SEQ ID NO: 5070), AGUgucugua (SEQ ID NO: 5071), CCCgugagcu (SEQ ID NO: 5072), GAGguucaca (SEQ ID NO: 5073), CUAgugggua (SEQ ID NO: 5074), GAGguaacua (SEQ ID NO: 5075), UCGguauguc (SEQ ID NO: 5076), UAAguauuug (SEQ ID NO: 5077), CAGguaagcg (SEQ ID NO: 5078), GAGgugguaa (SEQ ID NO: 5079), CGAguaagag (SEQ ID NO: 5080), CCGguaagcu (SEQ ID NO: 5081), GAGgucuugu (SEQ ID NO: 5082), AAGguggguc (SEQ ID NO: 5083), CACguaagug (SEQ ID NO: 5084), AGUguaauga (SEQ ID NO: 5085), AAAgugugua (SEQ ID NO: 5086), GGAgugccaa (SEQ ID NO: 5087), CACgugaguu (SEQ ID NO: 5088), AAGguuggau (SEQ ID NO: 5089), UAUguaaaua (SEQ ID NO: 5090), CUGguaggaa (SEQ ID NO: 5091), UAUguaaacu (SEQ ID NO: 5092), AAUguauuuu (SEQ ID NO: 5093), CUGgcaagug (SEQ ID NO: 5094), UGUgugguau (SEQ ID NO: 5095), UAUguauguu (SEQ ID NO: 5096), UUGgugacuc (SEQ ID NO: 5097), GGAguaaggu (SEQ ID NO: 5098), AAGguagaug (SEQ ID NO: 5099), UGGguagggu (SEQ ID NO: 5100), AAUguaauuc (SEQ ID NO: 5101), GUGguauggc (SEQ ID NO: 5102), GGAguggguu (SEQ ID NO: 5103), AGGguaccac (SEQ ID NO: 5104), UAGgugacag (SEQ ID NO: 5105), ACAguaggca (SEQ ID NO: 5106), AUGguuugaa (SEQ ID NO: 5107), GCAguaacua (SEQ ID NO: 5108), CCGguaggua (SEQ ID NO: 5109), AGAguaggcc (SEQ ID NO: 5110), AAGguugaca (SEQ ID NO: 5111), CUGgugugua (SEQ ID NO: 5112), GAAgucuguc (SEQ ID NO: 5113), UGGgcucgga (SEQ ID NO: 5114), CAGguagccu (SEQ ID NO: 5115), AGAguaggua (SEQ ID NO: 5116), UAAguauguc (SEQ ID NO: 5117), CUGguauauc (SEQ ID NO: 5118), GAGguguguu (SEQ ID NO: 5119), AUGgugcaug (SEQ ID NO: 5120), AAGguacgcc (SEQ ID NO: 5121), UGAguaacua (SEQ ID NO: 5122), GAGgugacag (SEQ ID NO: 5123), GUUguccugu (SEQ ID NO: 5124), UUGgugucuu (SEQ ID NO: 5125), AAUgugaagg (SEQ ID NO: 5126), UUGguggaua (SEQ ID NO: 5127), UAGguguguu (SEQ ID NO: 5128), CUGgcaaguu (SEQ ID NO: 5129), GCAguaagau (SEQ ID NO: 5130), GCGguggaaa (SEQ ID NO: 5131), UGCguccagc (SEQ ID NO: 5132), AAAguggagu (SEQ ID NO: 5133), CGUgugagcc (SEQ ID NO: 5134), AGAguacugu (SEQ ID NO: 5135), CAGguauagc (SEQ ID NO: 5136), UACguaagga (SEQ ID NO: 5137), AAGgucuuua (SEQ ID NO: 5138), AAGguggucu (SEQ ID NO: 5139), GGGguaaauu (SEQ ID NO: 5140), UCAgugagga (SEQ ID NO: 5141), AGAguacguu (SEQ ID NO: 5142), GAGgucguca (SEQ ID NO: 5143), UAGguuugau (SEQ ID NO: 5144), CAUguaaacc (SEQ ID NO: 5145), AAGguggcac (SEQ ID NO: 5146), CAGguagaug (SEQ ID NO: 5147), AACguaaaag (SEQ ID NO: 5148), UAGgucucug (SEQ ID NO: 5149), AUAguaggug (SEQ ID NO: 5150), UAGgcaagag (SEQ ID NO: 5151), UAGgcacggc (SEQ ID NO: 5152), AAGgucuuca (SEQ ID NO: 5153), CCAguaugcu (SEQ ID NO: 5154), CAAgugaguu (SEQ ID NO: 5155), CAGgucucaa (SEQ ID NO: 5156), CAGguuacau (SEQ ID NO: 5157), GGAgugagca (SEQ ID NO: 5158), AGAguacgca (SEQ ID NO: 5159), CUGguguugg (SEQ ID NO: 5160), AAGguacuca (SEQ ID NO: 5161), CUAguaaggg (SEQ ID NO: 5162), AGAguaaaag (SEQ ID NO: 5163), AAGguaacga (SEQ ID NO: 5164), CUGguccccg (SEQ ID NO: 5165), UAAguauggg (SEQ ID NO: 5166), GAGgucgagc (SEQ ID NO: 5167), UUGguauaua (SEQ ID NO: 5168), AAAgucaagg (SEQ ID NO: 5169), AAGgucuagg (SEQ ID NO: 5170), CGAguagguc (SEQ ID NO: 5171), AGGguucguu (SEQ ID NO: 5172), GAGgcaggcc (SEQ ID NO: 5173), CUAguauuac (SEQ ID NO: 5174), ACGguaugug (SEQ ID NO: 5175), UAGgugguuc (SEQ ID NO: 5176), AGAguauaac (SEQ ID NO: 5177), UUGgugcguc (SEQ ID NO: 5178), ACCguuaucu (SEQ ID NO: 5179), CCAgugauga (SEQ ID NO: 5180), GAAguaugca (SEQ ID NO: 5181), GAAguauggc (SEQ ID NO: 5182), CCGguaggac (SEQ ID NO: 5183), AAUguaagca (SEQ ID NO: 5184), AGAguaauug (SEQ ID NO: 5185), AGGguugguu (SEQ ID NO: 5186), GUGguaggag (SEQ ID NO: 5187), AAGgcaguuu (SEQ ID NO: 5188), CAAguaagcc (SEQ ID NO: 5189), CUGgcaagua (SEQ ID NO: 5190), CAGgcaugau (SEQ ID NO: 5191), AGGguaauug (SEQ ID NO: 5192), GGGguaaccu (SEQ ID NO: 5193), AAAguaacua (SEQ ID NO: 5194), UAGgucugcc (SEQ ID NO: 5195), ACGguaugaa (SEQ ID NO: 5196), AGUguauggg (SEQ ID NO: 5197), UGGguuggca (SEQ ID NO: 5198), UAGguaaacu (SEQ ID NO: 5199), AGAgugggua (SEQ ID NO: 5200), AGAguauuug (SEQ ID NO: 5201), AGUguaggaa (SEQ ID NO: 5202), CUUguacgua (SEQ ID NO: 5203), GAUgugagau (SEQ ID NO: 5204), CAGgcagcca (SEQ ID NO: 5205), AAGgucacug (SEQ ID NO: 5206), AAGgucugac (SEQ ID NO: 5207), UAGguuccuu (SEQ ID NO: 5208), CUGgugcuuu (SEQ ID NO: 5209), UGAguuggug (SEQ ID NO: 5210), UUGgugggau (SEQ ID NO: 5211), UGAguagggu (SEQ ID NO: 5212), UCGgugaggu (SEQ ID NO: 5213), AAAguaaaga (SEQ ID NO: 5214), AAGgcaaguc (SEQ ID NO: 5215), CGGguaaagc (SEQ ID NO: 5216), AAAguuaguu (SEQ ID NO: 5217), UUAguaagca (SEQ ID NO: 5218), GAGgucacau (SEQ ID NO: 5219), UAAgugguau (SEQ ID NO: 5220), UAGgugcuuu (SEQ ID NO: 5221), GGAguaggca (SEQ ID NO: 5222), UGAguaagga (SEQ ID NO: 5223), CAGguggagc (SEQ ID NO: 5224), GAUguagaag (SEQ ID NO: 5225), AAUgccugcc (SEQ ID NO: 5226), AUGguaaggc (SEQ ID NO: 5227), UGGguaauau (SEQ ID NO: 5228), CUGguaccuc (SEQ ID NO: 5229), CACgugagcc (SEQ ID NO: 5230), UGAguuugug (SEQ ID NO: 5231), CCGguagugu (SEQ ID NO: 5232), AAAgugacaa (SEQ ID NO: 5233), GAAguggguu (SEQ ID NO: 5234), CAGgugcagc (SEQ ID NO: 5235), GAGgugggcc (SEQ ID NO: 5236), UAUgugcguc (SEQ ID NO: 5237), GGGguacugg (SEQ ID NO: 5238), CUGguagguu (SEQ ID NO: 5239), UUGgcauguu (SEQ ID NO: 5240), AAUguaauac (SEQ ID NO: 5241), UAGgccggug (SEQ ID NO: 5242), AGAgucagua (SEQ ID NO: 5243), UAAguaaauc (SEQ ID NO: 5244), CAGguuccuc (SEQ ID NO: 5245), UAGguacgau (SEQ ID NO: 5246), AGAguuagug (SEQ ID NO: 5247), GCAguaagug (SEQ ID NO: 5248), AGGgugguag (SEQ ID NO: 5249), GGAguaaugu (SEQ ID NO: 5250), GAUguaaguc (SEQ ID NO: 5251), CCAguuucgu (SEQ ID NO: 5252), AAGguucggg (SEQ ID NO: 5253), AUGguggagu (SEQ ID NO: 5254), AAGguaccgg (SEQ ID NO: 5255), GAAgugcgaa (SEQ ID NO: 5256), UGGgucaguu (SEQ ID NO: 5257), AAGguguaga (SEQ ID NO: 5258), UGGguaggcc (SEQ ID NO: 5259), CCAgugaguc (SEQ ID NO: 5260), AAGgucacuu (SEQ ID NO: 5261), AGCgugaggc (SEQ ID NO: 5262), UCCgugguaa (SEQ ID NO: 5263), AGAguacuua (SEQ ID NO: 5264), GGGgucagau (SEQ ID NO: 5265), AAGguggacc (SEQ ID NO: 5266), AGAgugagcg (SEQ ID NO: 5267), AGAgucagau (SEQ ID NO: 5268), UAAguauuac (SEQ ID NO: 5269), AGAguauuuc (SEQ ID NO: 5270), AGAguucagc (SEQ ID NO: 5271), AUGgugaagu (SEQ ID NO: 5272), UAGgugaucc (SEQ ID NO: 5273), GGAguaagau (SEQ ID NO: 5274), UAGguaccaa (SEQ ID NO: 5275), AGAguugguc (SEQ ID NO: 5276), GAAgugagac (SEQ ID NO: 5277), AUCguagguu (SEQ ID NO: 5278), GAGguacgcu (SEQ ID NO: 5279), ACGguaaggg (SEQ ID NO: 5280), CAGgcauguc (SEQ ID NO: 5281), UUAguaagau (SEQ ID NO: 5282), UGAguagguu (SEQ ID NO: 5283), AGGguacgaa (SEQ ID NO: 5284), ACGguauguu (SEQ ID NO: 5285), AGGguacugu (SEQ ID NO: 5286), UUGguaugga (SEQ ID NO: 5287), UAAguaacug (SEQ ID NO: 5288), GCGgucagcc (SEQ ID NO: 5289), UUUgugaguc (SEQ ID NO: 5290), GUGgucagug (SEQ ID NO: 5291), CUGgucugua (SEQ ID NO: 5292), GAGguucuua (SEQ ID NO: 5293), AUGguacuga (SEQ ID NO: 5294), AAUgugcuuu (SEQ ID NO: 5295), AGGguggcgu (SEQ ID NO: 5296), CCGgcaggaa (SEQ ID NO: 5297), CAUguggguc (SEQ ID NO: 5298), UUGguuuguu (SEQ ID NO: 5299), CAGguucugu (SEQ ID NO: 5300), ACGguaagcg (SEQ ID NO: 5301), CUGgucagua (SEQ ID NO: 5302), UCAguaggcu (SEQ ID NO: 5303), UGAguaggac (SEQ ID NO: 5304), CAGguuuuaa (SEQ ID NO: 5305), GAGguguccc (SEQ ID NO: 5306), AGGguggguu (SEQ ID NO: 5307), GUGgugagac (SEQ ID NO: 5308), CACguaggga (SEQ ID NO: 5309), GUGguauuuu (SEQ ID NO: 5310), GAGauauccu (SEQ ID NO: 5311), AAGgugaaca (SEQ ID NO: 5312), UAAguagggc (SEQ ID NO: 5313), CUGgugcggg (SEQ ID NO: 5314), CUGgucaaua (SEQ ID NO: 5315), AGAguaaaaa (SEQ ID NO: 5316), AAGgugcagu (SEQ ID NO: 5317), CGGguaagca (SEQ ID NO: 5318), AAAgugagcc (SEQ ID NO: 5319), AUGguaauca (SEQ ID NO: 5320), GCAguacgug (SEQ ID NO: 5321), AUGguacaug (SEQ ID NO: 5322), AAGguuaaga (SEQ ID NO: 5323), CGGguaaaug (SEQ ID NO: 5324), GAGguucgca (SEQ ID NO: 5325), GAGgcucugg (SEQ ID NO: 5326), AUGgugggac (SEQ ID NO: 5327), AACgugguag (SEQ ID NO: 5328), AAGgugauag (SEQ ID NO: 5329), GGGguuugca (SEQ ID NO: 5330), CAUguaaggg (SEQ ID NO: 5331), UCAguugagu (SEQ ID NO: 5332), AAAgugcggc (SEQ ID NO: 5333), AGAgugagcc (SEQ ID NO: 5334), AUGgcaagaa (SEQ ID NO: 5335), ACAguaaggu (SEQ ID NO: 5336), AAGgucucua (SEQ ID NO: 5337), GUGguaaaaa (SEQ ID NO: 5338), AAAguaggug (SEQ ID NO: 5339), UAGgugcacu (SEQ ID NO: 5340), GUCgugguau (SEQ ID NO: 5341), CAGguauagg (SEQ ID NO: 5342), UGAgugagag (SEQ ID NO: 5343), ACUgugagcc (SEQ ID NO: 5344), AUCguuaguu (SEQ ID NO: 5345), UUUguaccaa (SEQ ID NO: 5346), UGGgugagau (SEQ ID NO: 5347), AGAgugagaa (SEQ ID NO: 5348), AGAguagggg (SEQ ID NO: 5349), AGGgcaagua (SEQ ID NO: 5350), CGGgucagua (SEQ ID NO: 5351), UUGguaugcc (SEQ ID NO: 5352), CGGguuagau (SEQ ID NO: 5353), GGGgugaagu (SEQ ID NO: 5354), CCCgugugaa (SEQ ID NO: 5355), GCAguuugga (SEQ ID NO: 5356), UGCguaagac (SEQ ID NO: 5357), AGAgucugua (SEQ ID NO: 5358), CACgugagca (SEQ ID NO: 5359), AGGguaaaag (SEQ ID NO: 5360), CAGgcugggu (SEQ ID NO: 5361), GAAgucuuca (SEQ ID NO: 5362), AAGgcaaaaa (SEQ ID NO: 5363), GUAguaaaua (SEQ ID NO: 5364), CUAgugagag (SEQ ID NO: 5365), GAAguuucug (SEQ ID NO: 5366), CCUguacgua (SEQ ID NO: 5367), GAGgugcgcg (SEQ ID NO: 5368), AAGguguaaa (SEQ ID NO: 5369), CCAguauguu (SEQ ID NO: 5370), CCGgucagcu (SEQ ID NO: 5371), AUGguuccug (SEQ ID NO: 5372), CAAguuaaau (SEQ ID NO: 5373), AGAguaggcu (SEQ ID NO: 5374), AUGgugggca (SEQ ID NO: 5375), GGAguaagac (SEQ ID NO: 5376), AGGgucacga (SEQ ID NO: 5377), UAGgugauau (SEQ ID NO: 5378), GAAguaaguc (SEQ ID NO: 5379), CGGguaagau (SEQ ID NO: 5380), CAAguagcua (SEQ ID NO: 5381), UGAguaaaau (SEQ ID NO: 5382), GUCguacgug (SEQ ID NO: 5383), AUGguacgua (SEQ ID NO: 5384), CAGgucucgg (SEQ ID NO: 5385), GAGgcauguc (SEQ ID NO: 5386), AGAgugggau (SEQ ID NO: 5387), GUGguuagag (SEQ ID NO: 5388), UGGgugguga (SEQ ID NO: 5389), AAGguuaaac (SEQ ID NO: 5390), CUUguuagcu (SEQ ID NO: 5391), AAAguaggaa (SEQ ID NO: 5392), UAGguuguau (SEQ ID NO: 5393), AGGgugcgcc (SEQ ID NO: 5394), AAGgugggcu (SEQ ID NO: 5395), UAAguaucug (SEQ ID NO: 5396), AAGguaacgu (SEQ ID NO: 5397), AUGguggggc (SEQ ID NO: 5398), CAAguacacg (SEQ ID NO: 5399), GGCguaagug (SEQ ID NO: 5400), AUAguaggac (SEQ ID NO: 5401), AGAgugaggu (SEQ ID NO: 5402), UUUguaaaaa (SEQ ID NO: 5403), GAAguuugua (SEQ ID NO: 5404), CUAguaaucu (SEQ ID NO: 5405), AAGguuuuua (SEQ ID NO: 5406), GAGgugcguu (SEQ ID NO: 5407), UAGgcgagua (SEQ ID NO: 5408), ACCgugagua (SEQ ID NO: 5409), CAGgucccga (SEQ ID NO: 5410), AUGguacugg (SEQ ID NO: 5411), UGAguucagu (SEQ ID NO: 5412), AAUguguggu (SEQ ID NO: 5413), UCCguugguu (SEQ ID NO: 5414), CAGgucagag (SEQ ID NO: 5415), CAGgucccua (SEQ ID NO: 5416), UAGguagacu (SEQ ID NO: 5417), CAAguuaagg (SEQ ID NO: 5418), GAGgugugcg (SEQ ID NO: 5419), GAAgcugccc (SEQ ID NO: 5420), CGAguacgug (SEQ ID NO: 5421), CGGguaggua (SEQ ID NO: 5422), UUGguauuga (SEQ ID NO: 5423), AUUguaugau (SEQ ID NO: 5424), UUGguaugaa (SEQ ID NO: 5425), GAGgugguca (SEQ ID NO: 5426), GCUguaugaa (SEQ ID NO: 5427), CAGguguugc (SEQ ID NO: 5428), CAGguaaaac (SEQ ID NO: 5429), AUAguaaggu (SEQ ID NO: 5430), CUGguuagag (SEQ ID NO: 5431), AGCgugugag (SEQ ID NO: 5432), AAGguuaucu (SEQ ID NO: 5433), CACgugagua (SEQ ID NO: 5434), AGGgucagua (SEQ ID NO: 5435), GAGguauaau (SEQ ID NO: 5436), CAGguuauuu (SEQ ID NO: 5437), AGGguggacu (SEQ ID NO: 5438), AUUguaauuc (SEQ ID NO: 5439), UUUguggguu (SEQ ID NO: 5440), AUGguacgug (SEQ ID NO: 5441), AAGguguucc (SEQ ID NO: 5442), CAGgugacgc (SEQ ID NO: 5443), GAGguacuaa (SEQ ID NO: 5444), ACAguucagu (SEQ ID NO: 5445), GAGgucacgg (SEQ ID NO: 5446), CAAguaaggc (SEQ ID NO: 5447), AAGguuuggg (SEQ ID NO: 5448), AAAgugggcu (SEQ ID NO: 5449), GCGguucuug (SEQ ID NO: 5450), GAGguggagc (SEQ ID NO: 5451), UGAgucagug (SEQ ID NO: 5452), CAGgucaagg (SEQ ID NO: 5453), AGUguaagcu (SEQ ID NO: 5454), GAGgcagaaa (SEQ ID NO: 5455), AAGgucacac (SEQ ID NO: 5456), GAAguagguu (SEQ ID NO: 5457), GUCguaaguu (SEQ ID NO: 5458), AGAguaugca (SEQ ID NO: 5459), CCUgugcaaa (SEQ ID NO: 5460), ACGgugaaaa (SEQ ID NO: 5461), CAGguacgaa (SEQ ID NO: 5462), CAUgugagga (SEQ ID NO: 5463), AGCgugagua (SEQ ID NO: 5464), GGUguguagg (SEQ ID NO: 5465), AACgugagcu (SEQ ID NO: 5466), GAGgugaacu (SEQ ID NO: 5467), AGAguucagu (SEQ ID NO: 5468), AACgugugua (SEQ ID NO: 5469), CAGguugugg (SEQ ID NO: 5470), AAGguacuag (SEQ ID NO: 5471), UCAgugaaaa (SEQ ID NO: 5472), AAUgucuggu (SEQ ID NO: 5473), ACGguaaaau (SEQ ID NO: 5474), CUGguguaag (SEQ ID NO: 5475), GAGgugcgaa (SEQ ID NO: 5476), AGGguuucuc (SEQ ID NO: 5477), CAGguagccc (SEQ ID NO: 5478), AUUguauugg (SEQ ID NO: 5479), AUGguacuua (SEQ ID NO: 5480), GAGgcccgac (SEQ ID NO: 5481), UCGguaagac (SEQ ID NO: 5482), CGGgcuguag (SEQ ID NO: 5483), UAUgugugug (SEQ ID NO: 5484), UAGguagaaa (SEQ ID NO: 5485), GUGgucauua (SEQ ID NO: 5486), UAGgugaaag (SEQ ID NO: 5487), ACUguaauuc (SEQ ID NO: 5488), GCAguacagg (SEQ ID NO: 5489), UCGgugaguc (SEQ ID NO: 5490), UAUguaggga (SEQ ID NO: 5491), AUGguauguc (SEQ ID NO: 5492), GUGgugugug (SEQ ID NO: 5493), CUGgugaccu (SEQ ID NO: 5494), AAUgugaaua (SEQ ID NO: 5495), UAGgucucac (SEQ ID NO: 5496), GAGguuauug (SEQ ID NO: 5497), UGAguaggcu (SEQ ID NO: 5498), CGGgcacgua (SEQ ID NO: 5499), GCAguaaaua (SEQ ID NO: 5500), CCGgugagag (SEQ ID NO: 5501), UAAguugguc (SEQ ID NO: 5502), CCGgugagcc (SEQ ID NO: 5503), AAGguuguca (SEQ ID NO: 5504), CUGguauuau (SEQ ID NO: 5505), GGGguauggg (SEQ ID NO: 5506), AAAgucagua (SEQ ID NO: 5507), UUUguaugua (SEQ ID NO: 5508), UAAguacugc (SEQ ID NO: 5509), CAGguaccaa (SEQ ID NO: 5510), GAAguucaga (SEQ ID NO: 5511), AUGgugcggu (SEQ ID NO: 5512), GUGgugaggu (SEQ ID NO: 5513), UGAguaagcc (SEQ ID NO: 5514), UAUguaaggg (SEQ ID NO: 5515), GUGguggaaa (SEQ ID NO: 5516), GAGgugauug (SEQ ID NO: 5517), GGAguuugua (SEQ ID NO: 5518), AAGgucacga (SEQ ID NO: 5519), GUGguagagg (SEQ ID NO: 5520), UAAguauauc (SEQ ID NO: 5521), AAGgugucca (SEQ ID NO: 5522), UAUgugguau (SEQ ID NO: 5523), GAGguacaau (SEQ ID NO: 5524), AAGguggggg (SEQ ID NO: 5525), GGAguaggug (SEQ ID NO: 5526), and UAGgugacuu (SEQ ID NO: 5527). In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises AGA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises AAA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises AAC. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises AAU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises AAG. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises ACA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises AUA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises AUU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises AUG. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises AUC. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CAA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CAU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CAC. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CAG. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises GAA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises GAC. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises GAU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises GAG. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises GGA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises GCA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises GGG. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises GGC. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises GUU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises GGU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises GUC. In some embodiments, the splice site sequence (e.g., 5 splice site sequence) comprises GUA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises GUG. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises UCU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises UCC. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises UCA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises UCG. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises UUU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises UUC. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises UUA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises UUG. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises UGU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises UAU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises GGA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CUU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CUC. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CUA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CUG. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CCU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CCC. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CCA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CCG. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises ACU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises ACC. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises ACG. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises AGC. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises AGU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises AGG. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CGU. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises UAC. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises UAA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises UAG. In some embodiments, the splice site sequence (e.g., 5 splice site sequence) comprises CGC. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CGA. In some embodiments, the splice site sequence (e.g., 5’ splice site sequence) comprises CGG. In some embodiments, the splice site sequence comprises AGAguaaggg (SEQ ID NO: 667). In some embodiments, the splice site sequence comprises UGAguaagca (SEQ ID NO: 2768). In an embodiment, a gene sequence or splice site sequence provided herein is related to a proliferative disease, disorder, or condition (e.g., cancer, benign neoplasm, or inflammatory disease). In an embodiment, a gene sequence or splice site sequence provided herein is related to a non-proliferative disease, disorder, or condition. In an embodiment, a gene sequence or splice site sequence provided herein is related to a neurological disease or disorder; autoimmune disease or disorder; immunodeficiency disease or disorder; lysosomal storage disease or disorder; cardiovascular condition, disease or disorder; metabolic disease or disorder; respiratory condition, disease, or disorder; renal disease or disorder; or infectious disease in a subject. In an embodiment, a gene sequence or splice site sequence provided herein is related to a neurological disease or disorder (e.g., Huntington’s disease). In an embodiment, a gene sequence or splice site sequence provided herein is related to an immunodeficiency disease or disorder. In an embodiment, a gene sequence or splice site sequence provided herein is related to a lysosomal storage disease or disorder. In an embodiment, a gene sequence or splice site sequence provided herein is related to a cardiovascular condition, disease or disorder. In an embodiment, a gene sequence or splice site sequence provided herein is related to a metabolic disease or disorder. In an embodiment, a gene sequence or splice site sequence provided herein is related to a respiratory condition, disease, or disorder. In an embodiment, a gene sequence or splice site sequence provided herein is related to a renal disease or disorder. In an embodiment, a gene sequence or splice site sequence provided herein is related to an infectious disease. In an embodiment, a gene sequence or splice site sequence provided herein is related to a mental retardation disorder. In an embodiment, a gene sequence or splice site sequence provided herein is related to a mutation in the SETD5 gene. In an embodiment, a gene sequence or splice site sequence provided herein is related to an immunodeficiency disorder. In an embodiment, a gene sequence and splice site sequence provided herein is related to a mutation in the GATA2 gene. In an embodiment, a gene sequence or splice site sequence provided herein is related to a lysosomal storage disease. In some embodiments, a compound of Formula (I) or (II) described herein interacts with (e.g., binds to) a splicing complex component (e.g., a nucleic acid (e.g., an RNA) or a protein). In some embodiments, the splicing complex component is selected from 9G8, Al hnRNP, A2 hnRNP, ASD-1, ASD-2b, ASF, BRR2, B1 hnRNP, C ₁ hnRNP, C ₂ hnRNP, CBP20, CBP80, CELF, F hnRNP, FBP11, Fox-1, Fox-2, G hnRNP, H hnRNP, hnRNP 1, hnRNP 3, hnRNP C, hnRNP G, hnRNP K, hnRNP M, hnRNP U, Hu, HUR, I hnRNP, K hnRNP, KH-type splicing regulatory protein (KSRP), L hnRNP, LUC7L, M hnRNP, mBBP, muscle-blind like (MBNL), NF45, NFAR, Nova-1, Nova-2, nPTB, P54/SFRS11, polypyrimidine tract binding protein (PTB), a PRP protein (e.g., PRP8, PRP6, PRP31, PRP4, PRP3, PRP28, PRP5, PRP2, PRP19), PRP19 complex proteins, RBM42, R hnRNP, RNPC ₁ , SAD1, SAM68, SC ₃ 5, SF, SF1/BBP, SF2, SF ₃ A complex, SF ₃ B complex, SFRS10, an Sm protein (such as B, D1, D2, D3, F, E, G), SNU17, SNU66, SNU114, an SR protein, SRm300, SRp20, SRp30c, SRP35C, SRP36, SRP38, SRp40, SRp55, SRp75, SRSF, STAR, GSG, SUP-12, TASR-1, TASR-2, TIA, TIAR, TRA2, TRA2a/b, U hnRNP, Ul snRNP, U11 snRNP, U12 snRNP, U1-70K, U1-A, U1-C, U2 snRNP, U2AF1-RS2, U2AF ₃ 5, U2AF65, U4 snRNP, U5 snRNP, U6 snRNP, Urp, and YB1. In some embodiments, the splicing complex component comprises RNA (e.g., snRNA). In some embodiments, a compound described herein binds to a splicing complex component comprising snRNA. The snRNA may be selected from, e.g., U1 snRNA, U2 snRNA, U4 snRNA, U5 snRNA, U6 snRNA, U11 snRNA, U12 snRNA, U4atac snRNA, and any combination thereof. In some embodiments, the splicing complex component comprises a protein, e.g., a protein associated with an snRNA. In some embodiments, the protein comprises SC ₃ 5, SRp55, SRp40, SRm300, SFRS10, TASR-1, TASR-2, SF2/ASF, 9G8, SRp75, SRp30c, SRp20 and P54/SFRS11. In some embodiments, the splicing complex component comprises a U2 snRNA auxiliary factor (e.g., U2AF65, U2AF ₃ 5), Urp/U2AF1-RS2, SF1/BBP, CBP80, CBP 20, SF1 or PTB/hnRNP1. In some embodiments, the hnRNP protein comprises A1, A2/B1, L, M, K, U, F, H, G, R, I or C ₁ /C ₂ . Human genes encoding hnRNPs include HNRNPA0, HNRNPA1, HNRNPA1L1, HNRNPA1L2, HNRNPA3, HNRNPA2B1, HNRNPAB, HNRNPB1, HNRNPC, HNRNPCL1, HNRNPD, HNRPDL, HNRNPF, HNRNPH1, HNRNPH2, HNRNPH3, HNRNPK, HNRNPL, HNRPLL, HNRNPM, HNRNPR, HNRNPU, HNRNPUL1, HNRNPUL2, HNRNPUL3, and FMR1. In one aspect, the compounds of Formula (I) or (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, and compositions thereof, may modulate (e.g., increase or decrease) a splicing event of a target nucleic acid sequence (e.g., DNA, RNA, or a pre-mRNA), for example, a nucleic acid encoding a gene described herein, or a nucleic acid encoding a protein described herein, or a nucleic acid comprising a splice site described herein. In an embodiment, the splicing event is an alternative splicing event. In an embodiment, the compound of Formula (I) or (II) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, and compositions thereof increases splicing at splice site on a target nucleic acid (e.g., an RNA, e.g., a pre-mRNA), by about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more, e.g., as determined by a known method in the art, e.g., qPCR. In an embodiment, the compound of Formula (I) or (II) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, and compositions thereof decreases splicing at splice site on a target nucleic acid (e.g., an RNA, e.g., a pre-mRNA), by about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more, e.g., as determined by a known method in the art, e.g., qPCR. In another aspect, the present disclosure features a method of forming a complex comprising a component of a spliceosome (e.g., a major spliceosome component or a minor spliceosome component), a nucleic acid (e.g., a DNA, RNA, e.g., a pre-mRNA), and a compound of Formula (I) or (II) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or composition thereof, comprising contacting the nucleic acid (e.g., a DNA, RNA, e.g., a pre-mRNA) with said compound of Formula (I) or (II). In an embodiment, the component of a spliceosome is selected from the U1, U2, U4, U5, U6, U11, U12, U4atac, U6atac small nuclear ribonucleoproteins (snRNPs), or a related accessory factor. In an embodiment, the component of a spliceosome is recruited to the nucleic acid in the presence of the compound of Formula (I) or (II) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or composition thereof. In another aspect, the present disclosure features a method of altering the conformation of a nucleic acid (e.g., a DNA, RNA, e.g., a pre-mRNA) comprising contacting the nucleic acid with a compound of Formula (I) or (II) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or composition thereof. In an embodiment, the altering comprises forming a bulge or kink in the nucleic acid. In an embodiment, the altering comprises stabilizing a bulge or a kink in the nucleic acid. In an embodiment, the altering comprises reducing a bulge or a kink in the nucleic acid. In an embodiment, the nucleic acid comprises a splice site. In an embodiment, the compound of Formula (I) or (II) interacts with a nucleobase, ribose, or phosphate moiety of a nucleic acid (e.g., a DNA, RNA, e.g., pre-mRNA). The present disclosure also provides methods for the treatment or prevention of a disease, disorder, or condition. In an embodiment, the disease, disorder or condition is related to (e.g., caused by) a splicing event, such as an unwanted, aberrant, or alternative splicing event. In an embodiment, the disease, disorder or condition comprises a proliferative disease (e.g., cancer, benign neoplasm, or inflammatory disease) or non-proliferative disease. In an embodiment, the disease, disorder, or condition comprises a neurological disease, autoimmune disorder, immunodeficiency disorder, cardiovascular condition, metabolic disorder, lysosomal storage disease, respiratory condition, renal disease, or infectious disease in a subject. In another embodiment, the disease, disorder, or condition comprises a haploinsufficiency disease, an autosomal recessive disease (e.g., with residual function), or a paralogue activation disorder. In another embodiment, the disease, disorder, or condition comprises an autosomal dominant disorder (e.g., with residual function). Such methods comprise the step of administering to the subject in need thereof an effective amount of a compound of Formula (I) or (II), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer thereof, or a pharmaceutical composition thereof. In certain embodiments, the methods described herein include administering to a subject an effective amount of a compound of Formula (I) or (II), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In certain embodiments, the subject being treated is a mammal. In certain embodiments, the subject is a human. In certain embodiments, the subject is a domesticated animal, such as a dog, cat, cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a companion animal such as a dog or cat. In certain embodiments, the subject is a livestock animal such as a cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a zoo animal. In another embodiment, the subject is a research animal such as a rodent, dog, or non-human primate. In certain embodiments, the subject is a non-human transgenic animal such as a transgenic mouse or transgenic pig. A proliferative disease may also be associated with inhibition of apoptosis of a cell in a biological sample or subject. All types of biological samples described herein or known in the art are contemplated as being within the scope of the disclosure. The compounds of Formula (I) or (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, and compositions thereof, may induce apoptosis, and therefore, be useful in treating and/or preventing proliferative diseases. In certain embodiments, the proliferative disease to be treated or prevented using the compounds of Formula (I) or (II) is cancer. As used herein, the term “cancer” refers to a malignant neoplasm (Stedman’s Medical Dictionary, 25th ed.; Hensyl ed.; Williams & Wilkins: Philadelphia, 1990). All types of cancers disclosed herein or known in the art are contemplated as being within the scope of the disclosure. Exemplary cancers include, but are not limited to, acoustic neuroma; adenocarcinoma; adrenal gland cancer; anal cancer; angiosarcoma (e.g., lymphangiosarcoma, lymphangioendotheliosarcoma, hemangiosarcoma); appendix cancer; benign monoclonal gammopathy; biliary cancer (e.g., cholangiocarcinoma); bladder cancer; breast cancer (e.g., adenocarcinoma of the breast, papillary carcinoma of the breast, mammary cancer, medullary carcinoma of the breast); brain cancer (e.g., meningioma, glioblastomas, glioma (e.g., astrocytoma, oligodendroglioma), medulloblastoma); bronchus cancer; carcinoid tumor; cervical cancer (e.g., cervical adenocarcinoma); choriocarcinoma; chordoma; craniopharyngioma; colorectal cancer (e.g., colon cancer, rectal cancer, colorectal adenocarcinoma); connective tissue cancer; epithelial carcinoma; ependymoma; endotheliosarcoma (e.g., Kaposi’s sarcoma, multiple idiopathic hemorrhagic sarcoma); endometrial cancer (e.g., uterine cancer, uterine sarcoma); esophageal cancer (e.g., adenocarcinoma of the esophagus, Barrett’s adenocarcinoma); Ewing’s sarcoma; eye cancer (e.g., intraocular melanoma, retinoblastoma); familiar hypereosinophilia; gall bladder cancer; gastric cancer (e.g., stomach adenocarcinoma); gastrointestinal stromal tumor (GIST); germ cell cancer; head and neck cancer (e.g., head and neck squamous cell carcinoma, oral cancer (e.g., oral squamous cell carcinoma), throat cancer (e.g., laryngeal cancer, pharyngeal cancer, nasopharyngeal cancer, oropharyngeal cancer), e.g., adenoid cystic carcinoma (ACC)); hematopoietic cancers (e.g., leukemia such as acute lymphocytic leukemia (ALL) (e.g., B-cell ALL, T-cell ALL), acute myelocytic leukemia (AML) (e.g., B-cell AML, T-cell AML), chronic myelocytic leukemia (CML) (e.g., B-cell CML, T-cell CML), and chronic lymphocytic leukemia (CLL) (e.g., B-cell CLL, T-cell CLL)); lymphoma such as Hodgkin lymphoma (HL) (e.g., B-cell HL, T-cell HL) and non-Hodgkin lymphoma (NHL) (e.g., B-cell NHL such as diffuse large cell lymphoma (DLCL) (e.g., diffuse large B-cell lymphoma), follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), marginal zone B-cell lymphomas (e.g., mucosa-associated lymphoid tissue (MALT) lymphomas, nodal marginal zone B-cell lymphoma, splenic marginal zone B-cell lymphoma), primary mediastinal B-cell lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma (i.e., Waldenström’s macroglobulinemia), hairy cell leukemia (HCL), immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma and primary central nervous system (CNS) lymphoma; and T-cell NHL such as precursor T-lymphoblastic lymphoma/leukemia, peripheral T-cell lymphoma (PTCL) (e.g., cutaneous T-cell lymphoma (CTCL) (e.g., mycosis fungoides, Sezary syndrome), angioimmunoblastic T-cell lymphoma, extranodal natural killer T-cell lymphoma, enteropathy type T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, and anaplastic large cell lymphoma); a mixture of one or more leukemia/lymphoma as described above; and multiple myeloma (MM)), heavy chain disease (e.g., alpha chain disease, gamma chain disease, mu chain disease); hemangioblastoma; hypopharynx cancer; inflammatory myofibroblastic tumors; immunocytic amyloidosis; kidney cancer (e.g., nephroblastoma a.k.a. Wilms’ tumor, renal cell carcinoma); liver cancer (e.g., hepatocellular cancer (HCC), malignant hepatoma); lung cancer (e.g., bronchogenic carcinoma, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), adenocarcinoma of the lung); leiomyosarcoma (LMS); mastocytosis (e.g., systemic mastocytosis); muscle cancer; myelodysplastic syndrome (MDS); mesothelioma; myeloproliferative disorder (MPD) (e.g., polycythemia vera (PV), essential thrombocytosis (ET), agnogenic myeloid metaplasia (AMM) a.k.a. myelofibrosis (MF), chronic idiopathic myelofibrosis, chronic myelocytic leukemia (CML), chronic neutrophilic leukemia (CNL), hypereosinophilic syndrome (HES)); neuroblastoma; neurofibroma (e.g., neurofibromatosis (NF) type 1 or type 2, schwannomatosis); neuroendocrine cancer (e.g., gastroenteropancreatic neuroendocrine tumor (GEP-NET), carcinoid tumor); osteosarcoma (e.g., bone cancer); ovarian cancer (e.g., cystadenocarcinoma, ovarian embryonal carcinoma, ovarian adenocarcinoma); papillary adenocarcinoma; pancreatic cancer (e.g., pancreatic adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), Islet cell tumors); penile cancer (e.g., Paget’s disease of the penis and scrotum); pinealoma; primitive neuroectodermal tumor (PNT); plasma cell neoplasia; paraneoplastic syndromes; intraepithelial neoplasms; prostate cancer (e.g., prostate adenocarcinoma); rectal cancer; rhabdomyosarcoma; salivary gland cancer; skin cancer (e.g., squamous cell carcinoma (SCC), keratoacanthoma (KA), melanoma, basal cell carcinoma (BCC)); small bowel cancer (e.g., appendix cancer); soft tissue sarcoma (e.g., malignant fibrous histiocytoma (MFH), liposarcoma, malignant peripheral nerve sheath tumor (MPNST), chondrosarcoma, fibrosarcoma, myxosarcoma); sebaceous gland carcinoma; small intestine cancer; sweat gland carcinoma; synovioma; testicular cancer (e.g., seminoma, testicular embryonal carcinoma); thyroid cancer (e.g., papillary carcinoma of the thyroid, papillary thyroid carcinoma (PTC), medullary thyroid cancer); urethral cancer; vaginal cancer; and vulvar cancer (e.g., Paget’s disease of the vulva). In some embodiments, the cancer is selected from adenoid cystic carcinoma (ACC), acute myelocytic leukemia (AML) (e.g., B-cell AML, T-cell AML), chronic myelocytic leukemia (CML) (e.g., B-cell CML, T-cell CML), non-Hodgkin lymphoma (NHL), Burkitt lymphoma, colorectal cancer (e.g., colon cancer, rectal cancer, colorectal adenocarcinoma), prostate cancer (e.g., prostate adenocarcinoma), ovarian cancer (e.g., cystadenocarcinoma, ovarian embryonal carcinoma, ovarian adenocarcinoma), and myelodysplastic syndrome (MDS). In some embodiments, the proliferative disease is associated with a benign neoplasm. For example, a benign neoplasm may include adenoma, fibroma, hemangioma, tuberous sclerosis, and lipoma. All types of benign neoplasms disclosed herein or known in the art are contemplated as being within the scope of the disclosure. In some embodiments, the proliferative disease is associated with angiogenesis. All types of angiogenesis disclosed herein or known in the art are contemplated as being within the scope of the disclosure. In some embodiments, the compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, or compositions comprising such compound or pharmaceutically acceptable salt thereof, is used to prevent or treat a non-proliferative disease. Exemplary non- proliferative diseases include a neurological disease, autoimmune disorder, immunodeficiency disorder, lysosomal storage disease, cardiovascular condition, metabolic disorder, respiratory condition, inflammatory disease, renal disease, or infectious disease. In certain embodiments, the non-proliferative disease is a neurological disease. In certain embodiments, the compound of Formula (I) or (II), or a pharmaceutically acceptable salt thereof, or compositions comprising such compound or pharmaceutically acceptable salt thereof, is used to prevent or treat a neurological disease, disorder, or condition. A neurological disease, disorder, or condition may include a neurodegenerative disease, a psychiatric condition, or a musculoskeletal disease. A neurological disease may further include a repeat expansion disease, e.g., which may be characterized by the expansion of a nucleic acid sequence in the genome. For example, a repeat expansion disease includes myotonic dystrophy, amyotrophic lateral sclerosis, Huntington’s disease, a trinucleotide repeat disease, or a polyglutamine disorder (e.g., ataxia, fragile X syndrome). In some embodiments, the neurological disease comprises a repeat expansion disease, e.g., Huntington’s disease. Additional neurological diseases, disorders, and conditions include Alzheimer’s disease, Huntington’s chorea, a prion disease (e.g., Creutzfeld- Jacob disease, bovine spongiform encephalopathy, Kuru, or scrapie), a mental retardation disorder (e.g., a disorder caused by a SETD5 gene mutation, e.g., intellectual disability-facial dysmorphism syndrome, autism spectrum disorder), Lewy Body disease, diffuse Lewy body disease (DLBD), dementia, progressive supranuclear palsy (PSP), progressive bulbar palsy (PBP), psuedobulbar palsy, spinal and bulbar muscular atrophy (SBMA), primary lateral sclerosis, Pick’s disease, primary progressive aphasia, corticobasal dementia, Parkinson’s disease, Down’s syndrome, multiple system atrophy, spinal muscular atrophy (SMA), progressive spinobulbar muscular atrophy (e.g., Kennedy disease), post-polio syndrome (PPS), spinocerebellar ataxia, pantothenate kinase-associated neurodegeneration (PANK), spinal degenerative disease/motor neuron degenerative diseases, upper motor neuron disorder, lower motor neuron disorder, Hallervorden-Spatz syndrome, cerebral infarction, cerebral trauma, chronic traumatic encephalopathy, transient ischemic attack, Lytigo-bodig (amyotrophic lateral sclerosis-parkinsonism dementia), Guam-Parkinsonism dementia, hippocampal sclerosis, corticobasal degeneration, Alexander disease, Apler’s disease, Krabbe’s disease, neuroborreliosis, neurosyphilis, Sandhoff disease, Tay-Sachs disease, Schilder’s disease, Batten disease, Cockayne syndrome, Kearns-Sayre syndrome, Gerstmann-Straussler-Scheinker syndrome and other transmissible spongiform encephalopathies, hereditary spastic paraparesis, Leigh’s syndrome, a demyelinating diseases, neuronal ceroid lipofuscinoses, epilepsy, tremors, depression, mania, anxiety and anxiety disorders, sleep disorders (e.g., narcolepsy, fatal familial insomnia), acute brain injuries (e.g., stroke, head injury), autism, Machado-Joseph disease, or a combination thereof. In some embodiments, the neurological disease comprises Friedrich s ataxia or Sturge Weber syndrome. In some embodiments, the neurological disease comprises Huntington’s disease. In some embodiments, the neurological disease comprises spinal muscular atrophy. All types of neurological diseases disclosed herein or known in the art are contemplated as being within the scope of the disclosure. In certain embodiments, the non-proliferative disease is an autoimmune disorder or an immunodeficiency disorder. In certain embodiments, the compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, or compositions comprising such compound or pharmaceutically acceptable salt thereof, is used to prevent or treat an autoimmune disease, disorder, or condition, or an immunodeficiency disease, disorder, or condition. Exemplary autoimmune and immunodeficiency diseases, disorders, and conditions include arthritis (e.g., rheumatoid arthritis, osteoarthritis, gout), Chagas disease, chronic obstructive pulmonary disease (COPD), dermatomyositis, diabetes mellitus type 1, endometriosis, Goodpasture’s syndrome, Graves’ disease, Guillain-Barrė syndrome (GBS), Hashiomoto’s disease, Hidradenitis suppurativa, Kawasaki disease, ankylosing spondylitis, IgA nephropathy, idiopathic thrombocytopenic purpura, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, collagenous colitis, lymphocytic colitis, ischemic colitis, diversion colitis, Behcet’s syndrome, infective colitis, indeterminate colitisinterstitial cystitis, lupus (e.g., systemic lupus erythematosus, discoid lupus, drug-induced lupus, neonatal lupus), mixed connective tissue disease, morphea, multiple sclerosis, myasthenia gravis, narcolepsy, neuromyotonia, pemphigus vulgaris, pernicious anemia, psoriasis, psoriatic arthritis, polymyositis, primary biliary cirrhosis, relapsing polychondritis, scleroderma, Sjögren’s syndrome, Stiff person syndrome, vasculitis, vitiligo, a disorder caused by a GATA2 mutation (e.g., GATA2 deficiency; GATA2 haploinsufficiency; Emberger syndrome; monocytopenia and mycobacterium avium complex/dendritic cell, monocyte, B and NK lymphocyte deficiency; familial myelodysplastic syndrome; acute myeloid leukemia; chronic myelomonocytic leukemia), neutropenia, aplastic anemia, and Wegener’s granulomatosis. In some embodiments, the autoimmune or immunodeficiency disorder comprises chronic mucocutaneous candidiasis. All types of autoimmune disorders and immunodeficiency disorders disclosed herein or known in the art are contemplated as being within the scope of the disclosure. In certain embodiments, the non-proliferative disease is a cardiovascular condition. In certain embodiments, the compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, or compositions comprising such compound or pharmaceutically acceptable salt thereof, is used to prevent or treat a cardiovascular disease, disorder, or condition. A cardiovascular disease, disorder, or condition may include a condition relating to the heart or vascular system, such as the arteries, veins, or blood. Exemplary cardiovascular diseases, disorders, or conditions include angina, arrhythmias (atrial or ventricular or both), heart failure, arteriosclerosis, atheroma, atherosclerosis, cardiac hypertrophy, cardiac or vascular aneurysm, cardiac myocyte dysfunction, carotid obstructive disease, endothelial damage after PTCA (percutaneous transluminal coronary angioplasty), hypertension including essential hypertension, pulmonary hypertension and secondary hypertension (renovascular hypertension, chronic glomerulonephritis), myocardial infarction, myocardial ischemia, peripheral obstructive arteriopathy of a limb, an organ, or a tissue; peripheral artery occlusive disease (PAOD), reperfusion injury following ischemia of the brain, heart or other organ or tissue, restenosis, stroke, thrombosis, transient ischemic attack (TIA), vascular occlusion, vasculitis, and vasoconstriction. All types of cardiovascular diseases, disorders, or conditions disclosed herein or known in the art are contemplated as being within the scope of the disclosure. In certain embodiments, the non-proliferative disease is a metabolic disorder. In certain embodiments, the compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, or compositions comprising such compound or pharmaceutically acceptable salt thereof, is used to prevent or treat a metabolic disease, disorder, or condition. A metabolic disease, disorder, or condition may include a disorder or condition that is characterized by abnormal metabolism, such as those disorders relating to the consumption of food and water, digestion, nutrient processing, and waste removal. A metabolic disease, disorder, or condition may include an acid- base imbalance, a mitochondrial disease, a wasting syndrome, a malabsorption disorder, an iron metabolism disorder, a calcium metabolism disorder, a DNA repair deficiency disorder, a glucose metabolism disorder, hyperlactatemia, a disorder of the gut microbiota. Exemplary metabolic conditions include obesity, diabetes (Type I or Type II), insulin resistance, glucose intolerance, lactose intolerance, eczema, hypertension, Hunter syndrome, Krabbe disease, sickle cell anemia, maple syrup urine disease, Pompe disease, and metachromatic leukodystrophy. All types of metabolic diseases, disorders, or conditions disclosed herein or known in the art are contemplated as being within the scope of the disclosure. In certain embodiments, the non-proliferative disease is a respiratory condition. In certain embodiments, the compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, or compositions comprising such compound or pharmaceutically acceptable salt thereof, is used to prevent or treat a respiratory disease, disorder, or condition. A respiratory disease, disorder, or condition can include a disorder or condition relating to any part of the respiratory system, such as the lungs, alveoli, trachea, bronchi, nasal passages, or nose. Exemplary respiratory diseases, disorders, or conditions include asthma, allergies, bronchitis, allergic rhinitis, chronic obstructive pulmonary disease (COPD), lung cancer, oxygen toxicity, emphysema, chronic bronchitis, and acute respiratory distress syndrome. All types of respiratory diseases, disorders, or conditions disclosed herein or known in the art are contemplated as being within the scope of the disclosure. In certain embodiments, the non-proliferative disease is a renal disease. In certain embodiments, the compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, or compositions comprising such compound or pharmaceutically acceptable salt thereof, is used to prevent or treat a renal disease, disorder, or condition. A renal disease, disorder, or condition can include a disease, disorder, or condition relating to any part of the waste production, storage, and removal system, including the kidneys, ureter, bladder, urethra, adrenal gland, and pelvis. Exemplary renal diseases include acute kidney failure, amyloidosis, Alport syndrome, adenovirus nephritis, acute lobar nephronia, tubular necrosis, glomerulonephritis, kidney stones, urinary tract infections, chronic kidney disease, polycystic kidney disease, and focal segmental glomerulosclerosis (FSGS). In some embodiments, the renal disease, disorder, or condition comprises HIV-associated nephropathy or hypertensive nephropathy. All types of renal diseases, disorders, or conditions disclosed herein or known in the art are contemplated as being within the scope of the disclosure. In certain embodiments, the non-proliferative disease is an infectious disease. In certain embodiments, the compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, or compositions comprising such compound or pharmaceutically acceptable salt thereof, is used to prevent or treat an infectious disease, disorder, or condition. An infectious disease may be caused by a pathogen such as a virus or bacteria. Exemplary infectious diseases include human immunodeficiency syndrome (HIV), acquired immunodeficiency syndrome (AIDS), meningitis, African sleeping sickness, actinomycosis, pneumonia, botulism, chlamydia, Chagas disease, Colorado tick fever, cholera, typhus, giardiasis, food poisoning, ebola hemorrhagic fever, diphtheria, Dengue fever, gonorrhea, streptococcal infection (e.g., Group A or Group B), hepatitis A, hepatitis B, hepatitis C, herpes simplex, hookworm infection, influenza, Epstein-Barr infection, Kawasaki disease, kuru, leprosy, leishmaniasis, measles, mumps, norovirus, meningococcal disease, malaria, Lyme disease, listeriosis, rabies, rhinovirus, rubella, tetanus, shingles, scarlet fever, scabies, Zika fever, yellow fever, tuberculosis, toxoplasmosis, or tularemia. In some embodiments, the infectious disease comprises cytomegalovirus. All types of infectious diseases, disorders, or conditions disclosed herein or known in the art are contemplated as being within the scope of the disclosure. In certain embodiments, the disease, disorder, or condition is a haploinsufficiency disease. In certain embodiments, the compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, or compositions comprising such compound or pharmaceutically acceptable salt thereof, is used to prevent or treat a haploinsufficiency disease, disorder, or condition. A haploinsufficiency disease, disorder, or condition may refer to a monogenic disease in which an allele of a gene has a loss-of-function lesion, e.g., a total loss of function lesion. In an embodiment, the loss-of-function lesion is present in an autosomal dominant inheritance pattern or is derived from a sporadic event. In an embodiment, the reduction of gene product function due to the altered allele drives the disease phenotype despite the remaining functional allele (i.e. said disease is haploinsufficient with regard to the gene in question). In an embodiment, a compound of Formula (I) or (II) increases expression of the haploinsufficient gene locus. In an embodiment, a compound of Formula (I) or (II) increases one or both alleles at the haploinsufficient gene locus. Exemplary haploinsufficiency diseases, disorders, and conditions include Robinow syndrome, cardiomyopathy, cerebellar ataxia, pheochromocytoma, Charcot-Marie-Tooth disease, neuropathy, Takenouchi-Kosaki syndrome, Coffin-Siris syndrome 2, chromosome 1p35 deletion syndrome, spinocerebellar ataxia 47, deafness, seizures, dystonia 9, GLUT1 deficiency syndrome 1, GLUT1 deficiency syndrome 2, stomatin-deficient cryohydrocytosis, basal cell carcinoma, basal cell nevus syndrome, medulloblastoma, somatic, brain malformations, macular degeneration, cone-rod dystrophy, Dejerine-Sottas disease, hypomyelinating neuropathy, Roussy-Levy syndrome, glaucoma, autoimmune lymphoproliferative syndrome, pituitary hormone deficiency, epileptic encephalopathy, early infantile, popliteal pterygium syndrome, van der Woude syndrome, Loeys-Dietz syndrome, Skraban-Deardorff syndrome, erythrocytosis, megalencephaly-polymicrogyria-polydactyly- hydrocephalus syndrome, mental retardation, CINCA syndrome, familial cold inflammatory syndrome 1, keratoendothelitis fugax hereditaria, Muckle-Wells syndrome, Feingold syndrome 1, Acute myeloid leukemia, Heyn-Sproul-Jackson syndrome, Tatton-Brown-Rahman syndrome, Shashi-Pena syndrome, Spastic paraplegia, autosomal dominant, macrophthalmia, colobomatous, with microcornea, holoprosencephaly, schizencephaly, endometrial cancer, familial, colorectal cancer, hereditary nonpolyposis, intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, ovarian hyperstimulation syndrome, schizophrenia, Dias-Logan syndrome, premature ovarian failure, dystonia, dopa-responsive, due to sepiapterin reductase deficiency, Beck-Fahrner syndrome, chromosome 2p12-p11.2 deletion syndrome, neuronopathy, spastic paraplegia, familial adult myoclonic, colorectal cancer, hypothyroidism, Culler-Jones syndrome, holoprosencephaly, myelokathexis, WHIM syndrome, Mowat-Wilson syndrome, mental retardation, an intellectual developmental disorder, autism spectrum disorder, epilepsy, epileptic encephalopathy, Dravet syndrome, migraines, a mental retardation disorder (e.g., a disorder caused by a SETD5 gene mutation, e.g., intellectual disability-facial dysmorphism syndrome, autism spectrum disorder), a disorder caused by a GATA2 mutation (e.g., GATA2 deficiency; GATA2 haploinsufficiency; Emberger syndrome; monocytopenia and mycobacterium avium complex/dendritic cell, monocyte, B and NK lymphocyte deficiency; familial myelodysplastic syndrome; acute myeloid leukemia; chronic myelomonocytic leukemia), and febrile seizures. In certain embodiments, the disease, disorder, or condition is an autosomal recessive disease, e.g., with residual function. In certain embodiments, the compound of Formula (I) or (II), or a pharmaceutically acceptable salt thereof, or compositions comprising such compound or pharmaceutically acceptable salt thereof, is used to prevent or treat an autosomal recessive disease, disorder, or condition. An autosomal recessive disease with residual function may refer to a monogenic disease with either homozygous recessive or compound heterozygous heritability. These diseases may also be characterized by insufficient gene product activity (e.g., a level of gene product greater than 0%). In an embodiment, a compound of Formula (I) or (II) may increase the expression of a target (e.g., a gene) related to an autosomal recessive disease with residual function. Exemplary autosomal recessive diseases with residual function include Friedreich’s ataxia, Stargardt disease, Usher syndrome, chlorioderma, fragile X syndrome, achromatopsia 3, Hurler syndrome, hemophilia B, alpha-1-antitrypsin deficiency, Gaucher disease, X-linked retinoschisis, Wiskott-Aldrich syndrome, mucopolysaccharidosis (Sanfilippo B), DDC deficiency, epidermolysis bullosa dystrophica, Fabry disease, metachromatic leukodystrophy, and odontochondrodysplasia. In certain embodiments, the disease, disorder, or condition is an autosomal dominant disease. In certain embodiments, the compound of Formula (I) or (II), or a pharmaceutically acceptable salt thereof, or compositions comprising such compound or pharmaceutically acceptable salt thereof, is used to prevent or treat an autosomal dominant disease, disorder, or condition. An autosomal dominant disease may refer to a monogenic disease in which the mutated gene is a dominant gene. These diseases may also be characterized by insufficient gene product activity (e.g., a level of gene product greater than 0%). In an embodiment, a compound of Formula (I) or (II) may increase the expression of a target (e.g., a gene) related to an autosomal dominant disease. Exemplary autosomal dominant diseases include Huntington’s disease, achondroplasia, antithrombin III deficiency, Gilbert’s disease, Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia, intestinal polyposis, hereditary elliptosis, hereditary spherocytosis, marble bone disease, Marfan’s syndrome, protein C deficiency, Treacher Collins syndrome, Von Willebrand’s disease, tuberous sclerosis, osteogenesis imperfecta, polycystic kidney disease, neurofibromatosis, and idiopathic hypoparathyroidism. In certain embodiments, the disease, disorder, or condition is a paralogue activation disorder. In certain embodiments, the compound of Formula (I) or (II), or a pharmaceutically acceptable salt thereof, or compositions comprising such compound or pharmaceutically acceptable salt thereof, is used to prevent or treat a paralogue activation disease, disorder, or condition. A paralogue activation disorder may comprise a homozygous mutation of genetic locus leading to loss-of-function for the gene product. In these disorders, there may exist a separate genetic locus encoding a protein with overlapping function (e.g. developmental paralogue), which is otherwise not expressed sufficiently to compensate for the mutated gene. In an embodiment, a compound of Formula (I) or (II) activates a gene connected with a paralogue activation disorder (e.g., a paralogue gene). The cell described herein may be an abnormal cell. The cell may be in vitro or in vivo. In certain embodiments, the cell is a proliferative cell. In certain embodiments, the cell is a cancer cell. In certain embodiments, the cell is a non-proliferative cell. In certain embodiments, the cell is a blood cell. In certain embodiments, the cell is a lymphocyte. In certain embodiments, the cell is a benign neoplastic cell. In certain embodiments, the cell is an endothelial cell. In certain embodiments, the cell is an immune cell. In certain embodiments, the cell is a neuronal cell. In certain embodiments, the cell is a glial cell. In certain embodiments, the cell is a brain cell. In certain embodiments, the cell is a fibroblast. In certain embodiment, the cell is a primary cell, e.g., a cell isolated from a subject (e.g., a human subject). In some embodiments, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has improved cell permeability over a reference compound, e.g., in a standard assay for measuring cell permeability. Cell permeability may be investigated, for example, using a standard assay run in either Madin-Darby Canine Kidney (MDCK) cells expressing Breast Cancer Resistance Protein (BCRP) or subclone MDCKII cells expressing Multidrug Resistance Protein 1 (MDR1); see, e.g., Drug Metabolism and Disposition 36, 268-275 (2008) and Journal of Pharmaceutical Sciences 1072225-2235 (2018). In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a cell permeability measurement (Papp) of < 2×10 ^-6 cm s ^-1 . In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a cell permeability measurement (Papp) of between 2-6×10 ^-6 cm s ^-1 . In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a cell permeability measurement (Papp) of Papp greater than 6×10 ^-6 cm s ^-1 . In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a cell permeability greater than 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%.85%, 90%, 95%, 99% or more, e.g., compared with a reference compound. In some embodiments, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, exhibits decreased cell efflux, e.g., over a reference compound, e.g., in a standard assay for measuring cell efflux. Cell efflux may be investigated, for example, using a standard assay run in either Madin-Darby Canine Kidney (MDCK) cells expressing Breast Cancer Resistance Protein (BCRP) or subclone MDCKII cells expressing Multidrug Resistance Protein 1 (MDR1); see, e.g., Drug Metabolism and Disposition 36, 268-275 (2008) and Journal of Pharmaceutical Sciences 1072225-2235 (2018). In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a cell efflux ratio of less than 1.5. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a cell efflux ratio of between 1.5 and 5. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a cell efflux ratio greater than 5. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a cell efflux ratio less than 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%.85%, 90%, 95%, 99% or more, e.g., compared with a reference compound. In some embodiments, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, modulates the expression of a target protein (e.g., HTT or MYB) in a reference cell or sample. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, increases the expression of a target protein (e.g., HTT or MYB) in a reference cell or sample. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, decreases the expression of a target protein (e.g., HTT or MYB) in a reference cell or sample. The effect of an exemplary compound of Formula (I) or (II) on protein abundance may be measured using a standard assay for measuring protein abundance, such as the HiBit-assay system (Promega). In this assay, percent response for each respective cell line may be as calculated at each compound concentration as follows: % response = 100 * (S – PC) / (NC – PC). For the normalized response at each concentration, a four-parameter logistical regression may be fit to the data and the response may be interpolated at the 50% value to determine a concentration for protein abundance at 50% (IC ₅₀ ) an untreated control. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a protein abundance response less than 100 nM. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a protein abundance response between 100-1000 nM. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a protein abundance response greater than 1000 nM. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a protein abundance response greater than 10 uM. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, modulates the protein abundance of a target protein by about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%. 85%, 90%, 95%, 99% or more, e.g., compared with a reference compound. In some embodiments, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, modulates the viability of a target cell in a subject or sample. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, increases the viability of a target cell in a subject or sample. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, decreases the viability of a target cell in a subject or sample. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, does not impact the viability of a cell (e.g., is non-toxic) in a subject or sample. The effect an exemplary compound of Formula (I) or (II) on cell viability may be measured using a standard assay for measuring cell toxicity, such as the Cell Titer Glo 2.0 assay in either K562 (human chronic myelogenous leukemia) or SH-SY5Y (human neuroblastoma) cells. The concentration at which cell viability is measured may be based on the particular assay used. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, is tolerated by a target cell at a concentration of less than 100 nM. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, is tolerated by a target cell at a concentration of between 100-1000 nM. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, is tolerated by a target cell at a concentration of greater than 1000 nM. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, is tolerated by a target cell at a concentration of greater than 10 uM. In some embodiments, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has improved brain permeability over a reference compound, e.g., in a standard assay for measuring brain permeability. Brain permeability may be measured, for example, by determining the unbound partition coefficient (Kpuu), brain. In such an assay, the unbound brain partition coefficient (K _p,uu,brain ) may be defined as the ratio of unbound brain-free compound concentration to unbound plasma concentration. It is calculated using the following equation: K p , uu , brain f u , plasma _^ C plasma C _brain and C _plasma represent the total concentrations in brain and plasma, respectively. In this assay, the fu,brain and fu,plasma may be the unbound fraction of the compound in brain and plasma, respectively. Both fu,brain and fu,plasma may be determined in vitro via equilibrium dialysis. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a Kp value of greater than 5. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a Kp value between 1 and 5. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a Kp value between 0.2-1. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a Kp value of less than 0.2. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a Kpuu value of greater than 2.5. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a Kpuu value between 0.5-2.5. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a Kpuu value between 0.1-0.5. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a Kpuu value of less than 0.1. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a brain permeability greater than 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%.85%, 90%, 95%, 99% or more, e.g., compared with a reference compound. In some embodiments, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, exhibits selectivity for one target nucleic acid sequence, e.g., pre-mRNA transcript sequence or bulge, compared to another target nucleic acid sequence, e.g., pre-mRNA transcript sequence or bulge. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, exhibits selectivity for HTT, e.g., an HTT-related nucleic acid sequence. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, exhibits selectivity for SMN2, e.g., an SMN2-related nucleic acid sequence. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, exhibits selectivity for Target C, e.g., a Target C-related nucleic acid sequence. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, exhibits selectivity for MYB, e.g., a MYB-related nucleic acid sequence. Selectivity for one target nucleic acid sequence over another may be measured using any number of methods known in the art. In an embodiment, selectivity may be measured by determining the ratio of derived qPCR values (e.g., as described herein) for one target nucleic acid sequence over another. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a ratio of greater than 1.1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, or 100 selectivity for one target nucleic acid sequence over another. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a ratio of greater than 1.1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, or 100 selectivity for HTT over another target nucleic acid sequence. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a ratio of greater than 1.1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, or 100 selectivity for SMN2 over another. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a ratio of greater than 1.1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, or 100 selectivity for MYB over another target nucleic acid sequence. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a ratio of greater than 1.1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, or 100 selectivity for Target C sequence over another. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a ratio of greater than 1.1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, or 100 selectivity for HTT over MYB. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a ratio of greater than 1.1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, or 100 selectivity for MYB over HTT. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a ratio of greater than 1.1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, or 100 selectivity for HTT over SMN2. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a ratio of greater than 1.1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, or 100 selectivity for SMN2 over HTT. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a ratio of greater than 1.1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, or 100 selectivity for SMN2 over MYB. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a ratio of greater than 1.1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, or 100 selectivity for MYB over SMN2. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a 3-fold greater selectivity for HTT over MYB. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a 3-fold greater selectivity for MYB over HTT. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a 10-fold greater selectivity for HTT over MYB. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a 10-fold greater selectivity for MYB over HTT. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a 3-fold greater selectivity for HTT over SMN2. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a 3-fold greater selectivity for SMN2 over HTT. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a 10-fold greater selectivity for HTT over SMN2. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a 10-fold greater selectivity for SMN2 over HTT. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a 3-fold greater selectivity for MYB over SMN2. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a 3-fold greater selectivity for SMN2 over MYB. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a 10-fold greater selectivity for MYB over SMN2. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a 10-fold greater selectivity for SMN2 over MYB. In an embodiment, a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, e.g., as described herein, has a selectivity for one target nucleic acid sequence that is greater than 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%.85%, 90%, 95%, 99% or more, e.g., compared with a second nucleic acid sequence. In certain embodiments, the methods described herein comprise the additional step of administering one or more additional pharmaceutical agents in combination with the compound of Formula (I) or (II), a pharmaceutically acceptable salt thereof, or compositions comprising such compound or pharmaceutically acceptable salt thereof. Such additional pharmaceutical agents include, but are not limited to, anti-proliferative agents, anti-cancer agents, anti-diabetic agents, anti-inflammatory agents, immunosuppressant agents, and a pain-relieving agent. The additional pharmaceutical agent(s) may synergistically augment the modulation of splicing induced by the inventive compounds or compositions of this disclosure in the biological sample or subject. Thus, the combination of the inventive compounds or compositions and the additional pharmaceutical agent(s) may be useful in treating, for example, a cancer or other disease, disorder, or condition resistant to a treatment using the additional pharmaceutical agent(s) without the inventive compounds or compositions. EXAMPLES In order that the invention described herein may be more fully understood, the following examples are set forth. The examples described in this application are offered to illustrate the compounds, pharmaceutical compositions, and methods provided herein and are not to be construed in any way as limiting their scope. The compounds provided herein can be prepared from readily available starting materials using modifications to the specific synthesis protocols set forth below that would be well known to those of skill in the art. It will be appreciated that where typical or preferred process conditions (i.e., reaction temperatures, times, mole ratios of reactants, solvents, pressures, etc.) are given, other process conditions can also be used unless otherwise stated. Optimum reaction conditions may vary with the particular reactants or solvents used, but such conditions can be determined by those skilled in the art by routine optimization procedures. Additionally, as will be apparent to those skilled in the art, conventional protecting groups may be necessary to prevent certain functional groups from undergoing undesired reactions. The choice of a suitable protecting group for a particular functional group as well as suitable conditions for protection and deprotection are well known in the art. For example, numerous protecting groups, and their introduction and removal, are described in Greene et al., Protecting Groups in Organic Synthesis, Second Edition, Wiley, New York, 1991, and references cited therein. Reactions can be purified or analyzed according to any suitable method known in the art. For example, product formation can be monitored by spectroscopic means, such as nuclear magnetic resonance (NMR) spectroscopy (e.g., ¹ H or ¹³ C), infrared (IR) spectroscopy, spectrophotometry (e.g., UV-visible), mass spectrometry (MS), or by chromatographic methods such as high performance liquid chromatography (HPLC) or thin layer chromatography (TLC). In some embodiments, absolute stereochemistry of chiral compounds provided herein is arbitrarily assigned. Proton NMR: ¹ H NMR spectra were recorded in CDCl ₃ solution in 5-mm o.d. tubes (Wildmad) at 24 °C and were collected on a BRUKER AVANCE NEO 400 at 400 MHz for ¹ H. The chemical shifts (δ) are reported relative to tetramethylsilane (TMS = 0.00 ppm) and expressed in ppm. LC/MS: Liquid chromatography-mass spectrometry (LC/MS) was performed on Shimadzu-2020EV using column: Shim-pack XR-ODS (C ₁₈ , Ø4.6 x 50 mm, 3 μm, 120 Å, 40 °C) operating in ESI(+) ionization mode; flow rate = 1.2 mL/min. Mobile phase = 0.05% TFA in water or CH ₃ CN; or on Shimadzu-2020EV using column : Poroshell HPH-C ₁₈ (C ₁₈ , Ø4.6 x 50 mm, 3 μm, 120 Å, 40 °C) operating in ESI(+) ionization mode; flow rate = 1.2 mL/min. Mobile phase A: Water/5mM NH4HCO ₃ , Mobile phase B: CH ₃ CN.) Reverse flash chromatography: Column: C ₁₈ silica gel. Condition 1: Mobile Phase A: water; Mobile Phase B: methanol. Gradient 1: 10% B to 50% B in 10 min. Condition 2: Mobile Phase A: methanol; Mobile Phase B: dichloromethane. Gradient 1: 0% B to 10% B in 10 min. Condition 3: Mobile Phase A: water (10 mmol/L NH4HCO ₃ ); Mobile Phase B: acetonitrile; Gradient 1: 20% B to 40% B in 30 min; Gradient 2: 10% B to 30% B in 20 min; Gradient 3: 10% B to 50% B in 10 min; Gradient 4: 10% B to 55% B in 10 min; Gradient 5: 20% B to 70% B in 12 min; Gradient 6: 10% B to 80% B in 25 min; Gradient 7: 30% B to 80% B in 30 min. Condition 4: Mobile Phase A: water (0.1% TFA); Mobile Phase B: acetonitrile; Gradient 1: 12% B to 51% B in 12 min; Gradient 2: 10% B to 55% B in 12 min; Gradient 3: 20% B to 60% B in 10 min; Gradient 4: 10% B to 50% B in 10 min; Gradient 5: 10% B to 30 % B in 10 min; Gradient 6: 20% B to 40% B in 10 min; Gradient 7: 30% B to 80% B in 12 min. Condition 5: Column: YMC-Actus Triart C ₁₈ , 30 x 150 mm, 5μm; Mobile Phase A: Water (10 mmol/L NH ₄ HCO ₃ ), Mobile Phase B: ACN; Flow rate: 60 mL/min; Gradient 1: 10% B to 60% B in 8 min; Gradient 2: 20% B to 60% B in 8 min; Gradient 3: 10% B to 50% B in 8 min; Gradient 4: 25% B to 58% B in 8 min; Gradient 5: 15% B to 71% B in 8 min. Condition 6: Column: Xselect CSH C ₁₈ OBD Column 30 x 150mm 5μm; Mobile Phase A: Water (10 mmol/L NH4HCO ₃ ), Mobile Phase B: ACN; Flow rate: 60 mL/min. Condition 7: Column: C ₁₈ silica gel; mobile phase, acetonitrile in water (0.1% FA), Gradient 1: 20% to 70% gradient in 12 min; Gradient 2: 20% to 65% gradient in 12 min; Gradient 3: 20% B to 50% B in 10 min; Gradient 4: 30% to 70% gradient in 12 min; Gradient 5: 30% B to 80% B in 10 min; Gradient 6: 60% B to 95% B in 12 min; Gradient 7: 5% B to 35% B in 12 min. Condition 8: Column, C ₁₈ ; mobile phase, MeCN in water (10mmol/L NH ₄ HCO ₃ ); Gradient 1: 10% B to 50% B in 10 min. Condition 9: Column, C ₁₈ silica gel; Mobile Phase A: water (0.1% NH ₃ .H ₂ O+10mmol/L NH ₄ HCO ₃ ), Mobile Phase B: Acetonitrile; Gradient 1: 10% B to 50% B in 12 min; Gradient 2: 20% B to 80% B in 10 min; Gradient 3: 5% B to 30% B in 10 min; Gradient 4: 20% B to 65% B in 10 min; Gradient 5: 30% B to 80% B in 12 min; Gradient 6: 40% B to 90% B in 12 min; Gradient 7: 15% B to 60% B in 12 min; Gradient 8: 20% B to 70% B in 12 min; Gradient 9: 30% B to 80% B in 10 min. Condition 10: Column, C ₁₈ silica gel; Mobile Phase A: Water (0.1% NH ₃ .H ₂ O), Mobile Phase B: Acetonitrile; Gradient 1: 20% B to 70% B in 10 min; Gradient 2: 15% B to 50% B in 10 min; Gradient 3: 10% B to 60% B in 10 min; Gradient 4: 20% B to 60% B in 10 min; Gradient 5: 10% B to 70% B in 10 min; Gradient 6: 30% B to 60% B in 10 min; Gradient 7: 30% B to 70% B in 10 min; Gradient 8: 30% B to 80% B in 10 min; Gradient 9: 20% B to 40% B in 10 min; Gradient 10: 10% B to 50% B in 10 min; Gradient 11: 40% B to 90% B in 12 min; Gradient 12: 20% B to 60% B in 12 min; Gradient 13: 10% B to 55% B in 12 min; Gradient 14: 10% B to 65% B in 10 min; Gradient 15: 30% B to 50% B in 10 min; Gradient 16: 50% B to 85% B in 8 min; Gradient 17: 30% B to 80% B in 12 min; Gradient 18: 40% B to 60% B in 10 min; Gradient 19:20% B to 50% B in 10 min; Gradient 20: 12% B to 67% B in 12 min; Gradient 21: 20% B to 90% B in 12 min; Gradient 22: 20% B to 65% B in 12 min; Gradient 23: 10% B to 50% B in 12 min; Gradient 24: 20% B to 70% B in 12 min; Gradient 25: 40% B to 90% B in 10 min; Gradient 26: 5% B to 55% B in 10 min; Gradient 27: 10% B to 55% B in 10 min. Condition 11: Column: XBridge BEH C ₁₈ OBD, 19 x 250 mm, 5um; Mobile Phase A: water (10 mmol/L NH4HCO ₃ ), Mobile Phase B: ACN; Gradient 1: 10% B to 50% B in 8 min. Condition 12: Column, C ₁₈ silica gel; Mobile Phase A: Water (0.1% TFA), Mobile Phase B: MeOH; Gradient 1: 10% B to 50% B in 10 min. Condition 13: Column, C ₁₈ silica gel; Mobile Phase A: water (0.1% NH ₃ .H ₂ O), Mobile Phase B: MeOH; Gradient 1: 10% B to 50% B in 10 min. Condition 14: Column, C ₁₈ silica gel; mobile phase A: water (0.1% HCl), Mobile Phase B: acetonitrile; Gradient 1: 20% B to 70% B in 12 min. Analytical chiral HPLC: Analytical chiral HPLC was performed on a Agilent 1260 using column: CHIRALPAK IG-3, CHIRALPAK IC-3 or CHIRALPAK OJ-3, with flow rate = 1.2 mL/min. Mobile phase = MTBE(DEA):EtOH=50:50). Preparative HPLC purification: prep-HPLC purification was performed on a Waters- 2545 or Shimadzu, using column: X-Select CSH C ₁₈ OBD (130Å, 5 µm, 30 mm x 150 mm), XBridge Prep OBD C ₁₈ (30 x 150mm, 5µm), XBridge Prep C ₁₈ OBD (5um, 19 mm x 150 mm), XBridge Shield RP18 OBD (1λ*150 mm, 5μm), or Kinetex EVO C ₁₈ Column (30*150 mm, 5μm). Condition 1: Column: XBridge Prep OBD C ₁₈ , 30 x150 mm, 5 µm; Mobile Phase A: water (10 mmol/L NH ₄ HCO ₃ ); Mobile Phase B: acetonitrile; Flow rate: 60 mL/min; Gradient 1: 45% B to 95% B in 8 min; Gradient 2: 5% B to 50% B in 8 min; Gradient 3: 5% B to 45% B in 8 min; Gradient 4: 5% B to 55% B in 8 min; Gradient 5: 5% B to 42% B in 8 min; Gradient 6: 5% B to 35% B in 8 min; Gradient 7: 5% B to 30% B in 8 min; Gradient 8: 20% B to 66% B in 8 min; Gradient 9: 10% B to 55% B in 8 min; Gradient 10: 5% B to 40% B in 8 min; Gradient 11: 10% B in 50% B in 8 min; Gradient 12: 20% B to 50% B in 8 min; Gradient 13: 25% B to 65% B in 8 min; Gradient 14: 5% B to 85% B in 8 min; Gradient 15: 10% B to 40% B in 8 min; Gradient 16: 5% B to 37% B; Gradient 17: 5% B to 38% B in 8 min; Gradient 18: 5% B to 45% B; Gradient 19: 10% B to 46% B in 8 min; Gradient 20: 10% B to 45% B in 10 min; Gradient 21: 15% B to 60% B in 8 min; Gradient 22: 35% B to 55% B in 10 min; Gradient 23: 10% B to 55% B in 8 min; Gradient 24: 20% B to 65% B in 8 min; Gradient 25: 25% B to 70% B in 8 min; Gradient 26: 10% B to 30% B in 10 min; Gradient 27: 30% B to 70% B in 8 min; Gradient 28: 10% B to 60% B in 8 min; Gradient 29: 15% B to 70% B in 8 min; Gradient 30: 25% B to 75% B in 8 min; Gradient 31: 35% B to 80% B in 8 min; Gradient 32: 30% B to 80% B in 8 min; Gradient 33: 15% B to 75% B in 8 min. Condition 2: Column: Xselect CSH OBD; Mobile Phase A: water (10 mmol/L NH4HCO ₃ ); Mobile Phase B: acetonitrile; Gradient 1: 5% B to 35% B in 8 min; Gradient 2: 10% B to 50% B in 8 min; Gradient 3: 5% B to 45% B in 8 min; Gradient 4: 10% B to 90% B in 8 min; Gradient 5: 15% B to 75% B in 8 min; Gradient 6: 25% B to 75% B in 8 min; Gradient 7: 15% B to 50% B in 8 min; Gradient 8: 3% B to 20% B in 8 min; Gradient 9: 5% B to 65% B in 8 min; Gradient 10: 45% B to 75% B in 8 min; Gradient 11: 30% B to 80% B in 8 min; Gradient 12: 20% B to 80% B in 8 min; Gradient 13: 15% B to 60% B in 8 min; Gradient 14: 5% B to 30% B in 8 min.. Condition 3: Column: YMC-Actus Triart C ₁₈ , 30 x 150 mm, 5μm; Mobile Phase A: water (10 mmol/L NH ₄ HCO ₃ ); Mobile Phase B: acetonitrile; Flow rate: 60 mL/min; Gradient 1: 10% B to 65% B in 8 min; Gradient 2: 5% B to 60% B in 8 min; Gradient 3: 5% B to 43% B in 8 min; Gradient 4: 5% B to 40% B in 8 min; Gradient 5: 5% B to 38% B in 8 min; Gradient 6: 5% B to 35% B in 8 min; Gradient 7: 5% B to 37% B in 8 min; Gradient 8: 5% B to 50% B in 8 min; Gradient 9: 5% B to 75% B in 8 min; Gradient 10: 5% B to 30% B in 8 min; Gradient 11: 3% B to 3% B in 2 min; Gradient 12: 3% B to 43% B in 8 min; Gradient 13: 15% B to 65% B in 8 min; Gradient 14: 40% B to 76% B in 8 min; Gradient 15: 10% B to 45% B in 8 min; Gradient 16: 5% B to 55% B in 8 min; Gradient 17: 5% B to 45% B in 8 min; Gradient 18: 10% B to 50% B in 8 min; Gradient 19: 5% B to 57% B in 8 min; Gradient 20: 15% B to 80% B in 8 min; Gradient 21: 10% B to 85% B in 8 min; Gradient 22: 20% B to 63% B in 8 min; Gradient 23: 30% B to 75% B in 10 min; Gradient 24: 30% B to 85% B in 8 min; Gradient 25: 35% B to 78% B in 8 min. Condition 4: Column: Xselect CSH OBD; Mobile Phase A: water (0.05% HCl); Mobile Phase B: acetonitrile; Gradient 1: 5% B to 30% B in 8 min; Gradient 2: 10% B to 50% B in 8 min; Gradient 3: 3% B to 43% B in 6 min; Gradient 4: 10% B to 60% B in 8 min. Condition 5: Column: SunFire Prep C ₁₈ OBD Column1λ*150 mm, 5μm 10 nm; Mobile Phase A: water (0.05%TFA), Mobile Phase B: acetonitrile; Gradient 1: 10% to 20% B in 7 min. Condition 6: Column: C ₁₈ silica gel, XBridge, 19 x 150 mm; Mobile Phase A: water (0.05% NH ₃ H ₂ O), Mobile Phase B: acetonitrile; Gradient 1: 30% to 70% B in 7 min; Gradient 2: 24% B to 54% B in 7 min; Gradient 3: 25% B to 55% B in 7 min; Gradient 4: 20% B to 58% B in 8 min; Gradient 5: 22% B to 62% B in 8 min; Gradient 6: 70% B to 90% B in 14 min; Gradient 7: 35% B to 55% B in 7 min; Gradient 8: 40% B to 65% B in 7 min; Gradient 9: 45% B to 70% B in 7 min; Gradient 10: 45% B to 65% B in 8 min; Gradient 11: 20% B to 40% B in 7 min; Gradient 12: 50% B to 70% B in 7 min; Gradient 13: 65% B to 85% B in 7 min; Gradient 14: 60% B to 85% B in 7 min; Gradient 15: 65% B to 90% B in 8 min; Gradient 16: 63% to 85% gradient in 8 min; Gradient 17: 20% B to 45% B in 7 min; Gradient 18: 38% B to 58% B in 7 min. Condition 7: Column: Welch Ultimate XB-C ₁₈ 50*250mm 10um; Mobile Phase A: water (0.1% TFA), Mobile Phase B: acetonitrile; Flow rate: 90mL/min; Gradient 1: 12% B to 47% B in 12 min; Gradient 2: 10% B to 45% B in 12 min; Gradient 3: 5% B isocratic for 2 min, 5% B to 30% B 12 min; Gradient 4: 20% B to 60% B in 12 min; Gradient 5: 25% B to 65% B in 12 min. Condition 8: Column: SunFire Prep C ₁₈ OBD 1λ*150 mm, 5μm 10 nm, Mobile Phase A: water (0.05% HCl), Mobile Phase B: acetonitrile; Gradient 1: 10% to 20% B in 12 min; Gradient 2: 48% B to 72% B in 12 min; Gradient 3: 10% B to 20% B in 7 min. Condition 9: Column: YMC-Actus Triart C ₁₈ , 30 x 150 mm, 5μm; Mobile Phase A: water (0.05% HCl); Mobile Phase B: Acetonitrile; Flow rate: 60 mL/min; Gradient 1: 10% B to 60% B in 8 min. Condition 10: Column: Xselect CSH OBD; Mobile Phase A: water (0.1% FA); Mobile Phase B: acetonitrile; Gradient 1: Hold 3% B for 2 min to 27% B in 6 min. Condition 11μ Xbridge Shield RP18 OBD Column, 30 x 150 mm, 5μm; Mobile Phase Aμ Water(10 mmol/L NH4HCO ₃ ), Mobile Phase B: acetonitrile; Flow rate: 60 mL/min; Gradient 1: 5% B to 40% B in 10 min; Gradient 2: 10% B to 45% B in 10 min; Gradient 3: 10% B to 60% B in 8 min; Gradient 4: 20% B to 75% B in 8 min; Gradient 5: 20% B to 55% B in 10 min. Condition 12: Column: Xselect CSH OBD; Mobile Phase A: water (0.05% HCl); Mobile Phase B: acetonitrile; Gradient 1: 5% B to 25% B in 8 min. Condition 13: Column: XBridge Prep OBD Column 19 x 150 mm, 8 µm; Mobile Phase A: water (0.1% NH ₃ ^. H ₂ O), Mobile Phase B: methanol; Flow rate: 20 mL/min; Gradient 1: 30% B to 80% B in 8 min; Gradient 2: 35% B to 75% B in 8 min; Gradient 3: 40% B to 80% B in 8 min; Gradient 4: 30% B to 60% B in 8 min; Gradient 5: 30% B to 70% B in 8 min; Gradient 6: 20% B to 75% B in 8 min. Condition 14: SunFire Prep Column 19*150 mm, 10nm; Mobile Phase A: water (0.05% NH ₄ OH), Mobile Phase B: acetonitrile; Gradient 1: 35% B to 50% B in 7 min. Condition 15: SunFire Prep Column19*150 mm, 10 nm; Mobile Phase A: water (0.05% NH4OH), Mobile Phase B: acetonitrile; Gradient 1: 35% B to 50% B in 7 min. Condition 16: Column: XBridge Shield RP18 OBD Column, 19*150 mm, 5μm; Mobile Phase A: water (10 mmol/L NH4HCO ₃ ), Mobile Phase B: ACN; Gradient 1: 20% B to 45% B in 8 min; Gradient 2: 15% B to 46% B in 8 min. Condition 17: Column: Kinetex EVO C ₁₈ Column, 30*150, 5μm; Mobile Phase A: water (10 mmol/L NH ₄ HCO ₃ ), Mobile Phase B: ACN; Gradient 1: 5% B to 35% B in 10 min; Gradient 2: 30% B to 65% B in 8 min. Condition 18: Column: CHIRALPAK IF-3, 4.6*50mm, 3um; Mobile Phase A: MtBE(0.1%DEA), Mobile Phase B, MeOH=85: 15; Flow rate: 1 mL/min; Gradient 1: 0% B to 0% B Condition 19: Column: C ₁₈ silica gel; Mobile Phase A: water (0.1% NH ₃ .H ₂ O+10 mmol/L NH ₄ HCO ₃ ), Mobile Phase B: acetonitrile; Gradient 1: 30% B to 80% B in 15 min. Condition 20: Column, C ₁₈ silica gel, XBridge, 19x150mm; Mobile Phase A: water (0.05% NH4HCO ₃ ), Mobile Phase B: acetonitrile; Gradient 1: 60% B to 80% B in 7 min; Preparative chiral HPLC: purification by chiral HPLC was performed on a Gilson-GX 281 using column: CHIRALPAK IG-3, CHIRALPAK IC-3 or CHIRALPAK OJ-3, YMC-Actus Triart C ₁₈ , Xselect CSH C ₁₈ OBD, XBridge Prep OBD C ₁₈ , or XBridge Shield RP18 OBD. Condition 1: Column: CHIRAL ART Cellulose-SB, 2 x 25 cm, 5 μm; Mobile Phase Aμ MtBE (0.1% DEA); Mobile Phase B: EtOH; Flow rate: 20 mL/min; Gradient 1: 30% B to 30% B in 7 min; Gradient 2: 15% B to 15% B in 7 min; Gradient 3: 0% B to 0% B; Gradient 4: 15% B to 15% B in 10 min; Gradient 5: 15% B to 15%B in 8 min; Gradient 6: 15% B to 15% B in 8.5 min; Gradient 7: 30% B to 30% B in 7 min; Gradient 8: 30% B to 30% B in 6.5 min; Gradient 9: 30% B to 30% B in 10.5 min; Gradient 10: 15% B to 15% B in 11 min; Gradient 11: 20% B to 20% B in 7.5 min; Gradient 12: 20% B to 20% B in 6.5 min; Gradient 13: 10% B to 10% B in 7.5 min; Gradient 14: 30% B isocratic in 11 min. Condition 2: Column: CHIRALPAK ID, 2*25 cm, 5 μm; Mobile Phase Aμ MtBE (0.1% DEA); Mobile Phase B: EtOH; Flow rate 1: 20 mL/min; Flow rate 2: Gradient 1: 20% B to 20% B in 15 min; Gradient 2: 0% B to 0% B. Condition 3: Column: CHIRALPAK IA-3, 4.6*50mm, 3 µm; Mobile Phase A: MtBE (0.1%DEA): EtOH=80: 20; Flow rate: 1 mL/min; Gradient 1: 0% B to 0% B; Gradient 2: 50% B isocratic in 20 min Condition 4: Column: CHIRAL ART Cellulose-SB, 2 x 25 cm, 5 μm; Mobile Phase Aμ MtBE (0.1% DEA); Mobile Phase B: Methanol; Flow rate: 20 mL/min; Gradient 1: 20% B isocratic 10 min; Gradient 2: 16% B isocratic in 8 min; Gradient 3: 25% B isocratic in 8 min; Gradient 4: 30% B isocratic in 7.5 min; Gradient 5: 40% B isocratic in 17 min; Gradient 6: 50% B isocratic in 7 min; Gradient 7: 40% B isocratic in 7 min; Gradient 8: 10% B in 17 min; Gradient 9: 35% B isocratic in 7.5 min; Gradient 10: 16% B isocratic in 9.5 min; Gradient 11: 20% B isocratic in 7 min; Gradient 12: 30% B isocratic in 6.5 min; Gradient 13: 25% B isocratic in 8.5 min; Gradient 14: 20% B isocratic in 9 min; Gradient 15: 50% B isocratic in 7.5 min. Condition 5: Column: CHIRAL ART Cellulose-SB, 4.6 x 100 mm, 3 μm; Mobile Phase A: MtBE(0.1%DEA): MeOH=60: 40; Flow rate: 1 mL/min; Gradient 1: 0% B to 0% B Condition 6: Column: CHIRALPAK IE, 2 x 25 cm, 5 μm; Mobile Phase Aμ MtBE(0.1% DEA), Mobile Phase B: MeOH; Flow rate: 20 mL/min; Gradient 1: 45% B to 45% B in 14.5 min; Gradient 2: 20% B isocratic in 27 min. Condition 7: Columnμ CHIRALPAK IG, 3 x 25 cm, 5 μm; Mobile Phase Aμ Hexμ DCM=1: 1, Mobile Phase B: EtOH (0.1% IPAmine); Flow rate: 35 mL/min; Gradient 1: 50% B isocratic in 40 min. Condition 8: Column, CHIRALPAK IC, 2 x 25 cm, 5 µm; Mobile Phase A, Hex (0.1% DEA) Mobile Phase B:EtOH; Gradient 1: 30% B isocratic in 9 min; Gradient 2: 50% B isocratic in 18.5 min. Condition 9: Column, YMC-Actus Triart C ₁₈ , 30 x 150 mm, 5µm; Mobile Phase A, water (10 mmol/L NH ₄ HCO ₃ ), Mobile Phase B, ACN; Gradient 1: 20% B to 63% B in 8 min; Gradient 2: 15% B to 55% B in 8 min. Condition 10: Column: CHIRAL ART Cellulose-SB, 2 x 25 cm, 5 μm; Mobile Phase A, MtBE (0.5% IPAmine), Mobile Phase B, MeOH; Gradient 1: 25% B isocratic 7 min. Condition 11: Column: Xselect CSH C ₁₈ OBD, 30 x 150 mm, 5 μm; Mobile Phase A, water (10 mmol/L NH4HCO ₃ ), Mobile Phase B, ACN; Gradient 1: 20% B to 80% B in 8 min. Condition 12: Column: XBridge Prep OBD C ₁₈ Column, 30 x 150 mm, 5µm; Mobile Phase A, water (10 mmol/L NH ₄ HCO ₃ ), and Mobile Phase B, ACN; Gradient 1: 20% ACN up to 70% in 8 min; Gradient 2: 34% B to 60% B in 8 min. Condition 13: Column: CHIRAL ART Cellulose-SB, 2*25 cm, 5 μm; Mobile Phase A, Hex(0.1% DEA), Mobile Phase B: EtOH; Gradient 1: 30% B isocratic 11 min. Condition 14: Column: XBridge Shield RP18 OBD Column, 30*150 mm, 5µm; Mobile phase A, water (10 mmol/L NH4HCO ₃ ), Mobile Phase B, ACN; Gradient 1: 10% B to 45% B in 10 min. Condition 15: Column: YMC Triart C ₁₈ ExRS, 20*150 mm, 5µm; Mobile phase A, water (10 mmol/L NH4HCO ₃ ), Mobile Phase B acetonitrile; Gradient 1: 20% B up to 63% B in 8 min. Condition 16: Columnμ CHIRALPAK IF, 2*25 cm, 5 μm; Mobile Phase Aμ MtBE(0.1% DEA), Mobile Phase B MeOH; Gradient 1: 15% B to 15% B in 19 min; Condition 17: Columnμ CHIRALPAK IG, 2*25 cm, 5 μm; Mobile Phase Aμ MtBE(0.1% DEA), Mobile Phase B: MeOH; Gradient 1: 30% B to 30% B in 17 min; Condition 18: Column: CHIRAL ART Cellulose-SZ, 3*25 cm, 5 μm; Mobile Phase Aμ CO ₂ , Mobile Phase B: MEOH: DCM=2: 1(0.1% 2M NH ₃ -MeOH); Gradient 1: isocratic 45% B. Condition 19: Column: XBridge Prep OBD C ₁₈ Column, 30*150 mm, 5μm; Mobile Phase A: Water(0.05%NH ₃ .H ₂ O), Mobile Phase B: ACN; Gradient 1: 10% B to 60% B in 8 min. Condition 20: Column: CHIRALPAK IH, 3*25 cm, 5 μm; Mobile Phase Aμ CO ₂ , Mobile Phase B: MEOH: DCM=2: 1(0.1% 2M NH ₃ -MeOH); Flow rate: 80 mL/min; Gradient 1: isocratic 40% B. Condition 21: Column: Kinetex EVO prep C ₁₈ , 30*150, 5um; Mobile Phase A: water (10 mmol/L NH ₄ HCO ₃ ), Mobile Phase B: CAN; Gradient 1: 25% B to 60% B in 8 min. General Schemes Compounds of the present disclosure may be prepared using a synthetic protocol illustrated below in Schemes A, B, C, D, E, F, and G. Scheme A. An exemplary method of preparing a representative compound of Formula (I-A); wherein A, and B are as defined herein, LG ¹ and LG ² are each independently a leaving group (e.g., halo); and –B(OR ¹² ) ₂ is a boronic ester (e.g., Bpin), wherein each R ¹² may be C ₁ -C ₆ -alkyl, C ₂ -C ₆ -heteroalkyl, aryl, or heteroaryl; or two R ¹² groups, together with the atoms to which they are attached, form a heterocyclyl or heteroaryl. An exemplary method of preparing a compound of Formula (I-A) is provided in Scheme A. In this scheme, A-3 is prepared by incubating A-1 with A-2 in the presence of a base, for example, potassium carbonate (K ₂ CO ₃ ) in dioxane and water or another suitable reagent. In some instances, A-3 is prepared by heating the reaction to a suitable temperature, for example, 80°C. Step 1 may also be carried out using an alternative catalyst to Pd ₂ (dba) ₃ , such as another palladium catalyst, for example, [1,1’-bis(di-tert-butylphosphino)ferrocene]dichloropalladi um(II) (Pd(dtbpf)Cl ₂ ) or chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1 ,1′-biphenyl)[2-(2′- amino-1,1′-biphenyl)]palladium(II) (XPhos-Pd-G2). The reaction may be conducted in DMF or a similar solvent, at 100 °C or a temperature sufficient to provide Fragment A-3, for example, 80 °C, 90 °C, 110 °C, or 120°C. The reaction may be conducted in a microwave reactor. In Step 2, A-3 and A-4 are coupled to provide a compound of Formula (I). This coupling reaction may be conducted in the presence of Pd(dppf)Cl ₂ , and K ₂ CO ₃ or a similar reagent, for example tripotassium carbonate (K3PO4). As in Step 1, alternative catalysts to Pd(dppf)Cl ₂ may be used, such as any suitable palladium catalyst, for example, tetrakis(triphenylphosphine)- palladium(0) (Pd(PPh ₃ ) ₄ ) or chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1 ,1′- biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (XPhos-Pd-G2). The reaction of Step 2 is conducted in dioxane or a mixture of dioxane and water, or other suitable solvents, and the mixture is heated to 80 °C or a temperature sufficient to provide the compound of Formula (I-A) or a precursor to the compound of Formula (I-A) with one or more protecting group(s), for example, 100 °C. Compounds of Formula (I-A) may be purified using standard techniques and characterized using any method known in the art, such as nuclear magnetic resonance spectroscopy (NMR) or mass spectrometry (MS). Scheme B. An exemplary method of preparing a representative compound of Formula (I-B); wherein A, and B are as defined herein, LG ¹ and LG ² are each independently a leaving group (e.g., halo); and –B(OR ¹² ) ₂ is a boronic ester (e.g., Bpin), wherein each R ¹² may be C ₁ -C ₆ -alkyl, C ₂ -C ₆ -heteroalkyl, aryl, or heteroaryl; or two R ¹² groups, together with the atoms to which they are attached, form a heterocyclyl or heteroaryl. An exemplary method of preparing a compound of Formula (I-B) is provided in Scheme B. In this scheme, the compound of Formula (I-B) is prepared by incubating A-1 with A-2 in the presence of a base, for example, potassium carbonate (K ₂ CO ₃ ) or another suitable reagent. In some instances, A-3 is prepared by heating the reaction to a suitable temperature, for example, 100°C. The reaction may be conducted in DMF or a similar solvent, at 100 °C or a temperature sufficient to provide the compound of Formula (I-B), for example, 80 °C, 90 °C, 110 °C, or 120°C to provide the compound of Formula (I-B) or a precursor to the compound of Formula (I- B) with one or more protecting group(s), for example, 100 °C. Compounds of Formula (I-B) may be purified using standard techniques and characterized using any method known in the art, such as nuclear magnetic resonance spectroscopy (NMR) or mass spectrometry (MS). The reaction may be conducted in a microwave reactor.

Scheme C. An exemplary method of preparing a representative compound of Formula (I-C); wherein A, and B are as defined herein, LG ¹ and LG ² are each independently a leaving group (e.g., halo); and –B(OR ¹² ) ₂ is a boronic ester (e.g., Bpin), wherein each R ¹² may be C ₁ -C ₆ -alkyl, C ₂ -C ₆ -heteroalkyl, aryl, or heteroaryl; or two R ¹² groups, together with the atoms to which they are attached, form a heterocyclyl or heteroaryl. Scheme D. An exemplary method of preparing a representative compound of Formula (I-D); wherein A, and B are as defined herein, LG ¹ and LG ² are each independently a leaving group (e.g., halo); and –B(OR ¹² ) ₂ is a boronic ester (e.g., Bpin), wherein each R ¹² may be C ₁ -C ₆ -alkyl, C ₂ -C ₆ -heteroalkyl, aryl, or heteroaryl; or two R ¹² groups, together with the atoms to which they are attached, form a heterocyclyl or heteroaryl. Scheme E. An exemplary method of preparing a representative compound of Formula (I-E); wherein A, and B are as defined herein, LG ¹ and LG ² are each independently a leaving group (e.g., halo); and –B(OR ¹² ) ₂ is a boronic ester (e.g., Bpin), wherein each R ¹² may be C ₁ -C ₆ -alkyl, C ₂ -C ₆ -heteroalkyl, aryl, or heteroaryl; or two R ¹² groups, together with the atoms to which they are attached, form a heterocyclyl or heteroaryl. Scheme F. An exemplary method of preparing a representative compound of Formula (I-F); wherein A, and B are as defined herein, LG ¹ and LG ² are each independently a leaving group (e.g., halo); and –B(OR ¹² ) ₂ is a boronic ester (e.g., Bpin), wherein each R ¹² may be C ₁ -C ₆ -alkyl, C ₂ -C ₆ -heteroalkyl, aryl, or heteroaryl; or two R ¹² groups, together with the atoms to which they are attached, form a heterocyclyl or heteroaryl. Scheme G. An exemplary method of preparing a representative compound of Formula (I-G); wherein A, and B are as defined herein, LG ¹ and LG ² are each independently a leaving group (e.g., halo); and –B(OR ¹² ) ₂ is a boronic ester (e.g., Bpin), wherein each R ¹² may be C ₁ -C ₆ -alkyl, C ₂ -C ₆ -heteroalkyl, aryl, or heteroaryl; or two R ¹² groups, together with the atoms to which they are attached, form a heterocyclyl or heteroaryl.

Scheme H. An exemplary method of preparing a representative compound of Formula (I-H); wherein A, B, R ³ , and n are as defined herein, LG ¹ and LG ² are each independently a leaving group such as halo, a boronic ester –B(OR ¹² ) ₂ (e.g., Bpin), wherein each R ¹² may be C ₁ -C ₆ -alkyl, C ₂ -C ₆ -heteroalkyl, aryl, or heteroaryl; or two R ¹² groups, together with the atoms to which they are attached, form a heterocyclyl or heteroaryl or hydrogen. Scheme J. An exemplary method of preparing a representative compound of Formula (I-J); wherein A, B, and R ² are as defined herein, each instance of LG ¹ and LG ² is each independently a leaving group such as halo, a boronic ester –B(OR ¹² ) ₂ (e.g., Bpin), wherein each R ¹² may be C ₁ -C ₆ -alkyl, C ₂ -C ₆ -heteroalkyl, aryl, or heteroaryl; or two R ¹² groups, together with the atoms to which they are attached, form a heterocyclyl or heteroaryl or hydrogen. Scheme K. An exemplary method of preparing a representative compound of Formula (I-K); wherein A, B, R ³ , and n are as defined herein, LG ¹ and LG ² are each independently a leaving group such as halo, a boronic ester –B(OR ¹² ) ₂ (e.g., Bpin), wherein each R ¹² may be C ₁ -C ₆ -alkyl, C ₂ -C ₆ -heteroalkyl, aryl, or heteroaryl; or two R ¹² groups, together with the atoms to which they are attached, form a heterocyclyl or heteroaryl or hydrogen. Scheme L. An exemplary method of preparing a representative compound of Formula (I-L); wherein A, B, and R ^A are as defined herein, each instance of LG ¹ and LG ² is each independently a leaving group such as halo, a boronic ester –B(OR ¹² ) ₂ (e.g., Bpin), wherein each R ¹² may be C ₁ -C ₆ -alkyl, C ₂ -C ₆ -heteroalkyl, aryl, or heteroaryl; or two R ¹² groups, together with the atoms to which they are attached, form a heterocyclyl or heteroaryl or hydrogen. Exemplary methods of preparing a compound of Formula (I) or (II) are provided in Schemes A-G. Coupling of Ring A or Ring B to the core may be carried out with a catalyst, for example, a palladium catalyst, such as Pd ₂ (dba) ₃ , tetrakis(triphenylphosphine)-palladium(0) (Pd(PPh3)4), 1,1’-bis(diphenylphosphino)ferrocene)palladium(II) dichloride (Pd(dppf)Cl ₂ ), [1,1’- bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (Pd(dtbpf)Cl ₂ ), Pd-PEPPSI-IPentCl 2-methylpyridine o-picoline, chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1 ,1′- biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (XPhos-Pd-G2), SPhos-Pd-G3, or XPhos-Pd- G3, and/or a copper catalyst, such as CuI or Cu(OAc) ₂ in the presence or absence of a nitrogenous ligand. One or more bases, such as potassium carbonate, cesium carbonate, potassium phosphate, or triethyl amine, may also be present. Coupling reactions may be conducted in a solvent, such as DMA, DMF, DCM, THF, toluene, dioxane, water, or a similar solvent or mixtures of solvents, at room temperature or a temperature sufficient to provide the compound of Formula (I) or (II), for example, 80 °C, 90 °C, 100 °C, 110 °C, or 120°C. The reaction may be conducted in a microwave reactor. Compounds of Formula (I) or (II) may be purified using standard techniques and characterized using any method known in the art, such as nuclear magnetic resonance spectroscopy (NMR) or mass spectrometry (MS). Examples 1-102 describing exemplary protocols for Compound 100-282 are provided in WO 2022/006550, which is incorporated herein by reference in its entirety. Example 103: Synthesis of Compound 343 Synthesis of Intermediate C1 A mixture of 5-bromo-2-chloropyridin-3-amine (15.00 g, 72.30 mmol, 1 equiv), Boc ₂ O (34.70 g, 159.06 mmol, 2.2 equiv), Et3N (21.90 g, 216.90 mmol, 3 equiv), and DMAP (0.86 g, 7.23 mmol, 0.1 equiv) in DCM (150 mL) was stirred overnight at room temperature. The resulting mixture was diluted with water (100 mL) and extracted with CH ₂ Cl ₂ (3 x 100 mL). The organic layers were combined, washed with brine (1 x 100 mL), dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:2) to afford tert-butyl N-(5-bromo-2-chloropyridin-3-yl)-N-(tert-butoxycarbonyl)carb amate (21.90 g, 74%) as a solid. LCMS (ES, m/z): 407 [M+H] ⁺ . Synthesis of Intermediate C2 To a stirred mixture of tert-butyl N-(5-bromo-2-chloropyridin-3-yl)-N-(tert- butoxycarbonyl)carbamate (21.90 g, 53.71 mmol, 1 equiv) and B(OMe) ₃ (16.70 g, 161.15 mmol, 3 equiv) in THF (440 mL) was added n-BuLi (64.6 mL) dropwise at -78 °C under nitrogen atmosphere. The resulting mixture was stirred for 2 h at -78 °C under nitrogen atmosphere. The reaction mixture was quenched with sat. NH4Cl (aq.) at 0 °C, then acidified to pH 3 with 2 M HCl (aq.) and extracted with ethyl acetate (3 x 1000 mL). The organic layers were combined, washed with brine (1x1000 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to afford 5-[bis(tert-butoxycarbonyl)amino]-6- chloropyridin-3-ylboronic acid (24.3 g, 100%) as an oil. LCMS (ES, m/z): 373 [M+H] ⁺ . Synthesis of Intermediate C3 To a stirred mxiture of 5-[bis(tert-butoxycarbonyl)amino]-6-chloropyridin-3-ylboroni c acid (24.30 g, 65.21 mmol, 1 equiv) and 2 M NaOH (24 mL) in THF (240 mL) was added H ₂ O ₂ (30%) (120 mL) dropwise at 0 °C. The resulting mixture was stirred for 3 hr at room temperature, then quenched with sat. NaHSO ₃ (aq.) at 0 °C and extracted with ethyl acetate (3 x 300 mL). The organic layers were combined, washed with brine (1 x 300 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to afford tert-butyl N-(tert-butoxycarbonyl)-N-(2-chloro-5-hydroxypyridin-3- yl)carbamate (19.00 g, 85%) as an oil. LCMS (ES, m/z): 345 [M+H] +. Synthesis of Intermediate C4

To a stirred mixture of tert-butyl N-(tert-butoxycarbonyl)-N-(2-chloro-5-hydroxypyridin-3- yl)carbamate (19.00 g, 55.10 mmol, 1 equiv) and Na ₂ CO ₃ (29.20 g, 275.53 mmol, 5 equiv) in DMF (200 mL) was added CH ₃ I (39.10 g, 275.53 mmol, 5 equiv) dropwise at 0 °C under nitrogen atmosphere. The resulting mixture was stirred overnight at room temperature under nitrogen atmosphere, then diluted with water (200 mL) and extracted with ethyl acetate (3 x 200 mL). The organic layers were combined, washed with brine (1 x 200 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:2) to afford tert-butyl N-(tert-butoxycarbonyl)-N-(2-chloro-5-methoxypyridin-3-yl)ca rbamate (10.2 g, 52%) as a solid. LCMS (ES, m/z): 359 [M+H] ⁺ . Synthesis of Intermediate C5 To a solution of tert-butyl N-(tert-butoxycarbonyl)-N-(2-chloro-5-methoxypyridin-3- yl)carbamate (10.20 g, 28.42 mmol, 1 equiv) in methanol (100 mL) was added Et ₃ N (14.40 g, 142.13 mmol, 5 equiv) and Pd(dppf)Cl ₂ CH ₂ Cl ₂ (1.20 g, 1.42 mmol, 0.05 equiv) in a pressure tank. The mixture was purged with nitrogen for 30 min, then was pressurized to 1.5 MPa with carbon monoxide and heated at 90 °C overnight. The reaction mixture was cooled to room temperature. A precipitate formed that was collected to afford methyl 3-[(tert- butoxycarbonyl)amino]-5-methoxypyridine-2-carboxylate (4.40 g, 55%) as a solid. LCMS (ES, m/z): 283 [M+H] ⁺ . Synthesis of Intermediate C6 A mixture of methyl 3-[(tert-butoxycarbonyl)amino]-5-methoxypyridine-2-carboxyla te (4.40 g, 15.58 mmol, 1 equiv), NBS (3.10 g, 17.14 mmol, 1.1 equiv), and AcOH (4.4 mL) in DMF (44 mL) was stirred overnight at 60 °C. The resulting mixture was diluted with water (100 mL) and extracted with ethyl acetate (3 x 100 mL). The organic layers were combined, washed with brine (1x100 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (3:2) to afford methyl 6-bromo-3-[(tert- butoxycarbonyl)amino]-5-methoxypyridine-2-carboxylate (3.37 g, 60%) as a solid. LCMS (ES, m/z): 361 [M+H] ⁺ . Synthesis of Intermediate C7 To a stirred solution of methyl 6-bromo-3-[(tert-butoxycarbonyl)amino]-5-methoxypyridine-2- carboxylate (3.37 g, 9.33 mmol, 1 equiv) in DCM (70 mL) was added DIBAl-H (7.96 g, 55.98 mmol, 6 equiv) dropwise at -40 °C under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 0 °C under nitrogen atmosphere. The resulting mixture was diluted with water (100 mL), neutralized to pH 8 with 2 M NaOH, and extracted with CH ₂ Cl ₂ (3 x 100 mL). The organic layers were combined, washed with brine (1 x 100 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (20:1) to afford tert-butyl N-[6-bromo-2-(hydroxymethyl)-5-methoxypyridin-3-yl]carbamate (1.84 g, 59%) as a solid. LCMS (ES, m/z): 333 [M+H] ⁺ . Synthesis of Intermediate C8 A mixture of tert-butyl N-[6-bromo-2-(hydroxymethyl)-5-methoxypyridin-3-yl]carbamate (1.84 g, 5.52 mmol, 1 equiv) and DMP (2.81 g, 6.62 mmol, 1.2 equiv) in DCM (20 mL) was stirred overnight at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (20:1) to afford tert-butyl N-(6-bromo-2-formyl-5- methoxypyridin-3-yl)carbamate (1.60 g, 88%) as a solid. LCMS (ES, m/z): 331 [M+H] ⁺ . Synthesis of Intermediate C9 A mixture of tert-butyl N-(6-bromo-2-formyl-5-methoxypyridin-3-yl)carbamate (1.60 g, 4.83 mmol, 1 equiv) and ethyl 2-(triphenyl-lambda5-phosphanylidene)acetate (2.19 g, 6.28 mmol, 1.3 equiv) in toluene (16 mL) was stirred for 5 h at room temperature. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (5:1) to afford ethyl (2E)-3-{6-bromo-3-[(tert- butoxycarbonyl)amino]-5-methoxypyridin-2-yl}prop-2-enoate (1.3 g, 67%) as a solid. LCMS (ES, m/z): 401 [M+H] ⁺ . Synthesis of Intermediate C10 A solution of ethyl (2E)-3-{6-bromo-3-[(tert-butoxycarbonyl)amino]-5-methoxypyri din-2- yl}prop-2-enoate (1.30 g, 3.24 mmol, 1 equiv) in 10% HCl (26 mL) and ethanol (6.5 mL) was stirred overnight at 100 °C. The resulting mixture was filtered, and the filter cake washed with water (3 x 20 mL), followed by PE (3x20 mL). The filtrate was concentrated under reduced pressure to afford 6-bromo-7-methoxy-1,5-naphthyridin-2-ol (600 mg, 73%) as a solid. LCMS (ES, m/z): 255 [M+H] ⁺ . Synthesis of Intermediate C11 A mixture of 2-bromo-4,6-dimethylpyrazolo[1,5-a]pyrazine (500 mg, 2.21 mmol, 1 equiv), Sn2Me6 (1086.9 mg, 3.31 mmol, 1.5 equiv), and Pd(DtBPF)Cl ₂ (144.1 mg, 0.22 mmol, 0.1 equiv) in dioxane (10 mL) was stirred for 2 hr at 100 °C under nitrogen atmosphere. The reaction mixture was quenched with sat. KF (aq.)(30 mL) at room temperature and extracted with CH ₂ Cl ₂ (3 x 30 mL). The organic layers were combined, washed with brine (1x30 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to afford 4,6-dimethyl-2-(trimethylstannyl)pyrazolo[1,5-a]pyrazine (680 mg, Crude) as an oil. LCMS (ES, m/z): 312 [M+H] ⁺ . Synthesis of Intermediate C12 A mixture of 6-bromo-7-methoxy-1,5-naphthyridin-2-ol (300 mg, 1.17 mmol, 1 equiv), 4,6- dimethyl-2-(trimethylstannyl)pyrazolo[1,5-a]pyrazine (401.0 mg, 1.29 mmol, 1.1 equiv), and Pd(DtBPF)Cl ₂ (76.6 mg, 0.12 mmol, 0.1 equiv) in dioxane (3 mL) was stirred for 2 hr at 100 °C under nitrogen atmosphere. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ / MeOH (5:1) to afford 6-{4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl}-7-methoxy-1,5- naphthyridin-2-ol (240 mg, 64%) as a solid. LCMS (ES, m/z): 322 [M+H] ⁺ . Synthesis of Intermediate C13 A solution of 6-{4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl}-7-methoxy-1,5-na phthyridin-2-ol (230 mg, 0.71 mmol, 1 equiv) in POCl ₃ (3 mL) was stirred for 3 hr at 80 °C. The resulting mixture was concentrated under vacuum to give a reisdue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ /MeOH (5:1) to afford 6-chloro-2-{4,6- dimethylpyrazolo[1,5-a]pyrazin-2-yl}-3-methoxy-1,5-naphthyri dine (300 mg, 100%) as an oil. LCMS (ES, m/z): 340 [M+H] ⁺ . A mixture of 6-chloro-2-{4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl}-3-metho xy-1,5- naphthyridine (255 mg, 0.75 mmol, 1 equiv), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (348.1 mg, 1.12 mmol, 1.5 equiv), K3PO4 (477.9 mg, 2.25 mmol, 3 equiv) and XPhos Precatalyst (2nd Generation, 59.0 mg, 0.07 mmol, 0.1 equiv) in dioxane (2 mL) and water (0.5 mL) was stirred overnight at 100 °C under nitrogen atmosphere. The resulting mixture was diluted with water (20 mL) and extracted with ethyl acetate (3 x 20 mL). The organic layers were combined, washed with brine (1 x 20 mL), dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:2) to afford tert-butyl 4-(6-{4,6-dimethylpyrazolo[1,5- a]pyrazin-2-yl}-7-methoxy-1,5-naphthyridin-2-yl)-3,6-dihydro -2H-pyridine-1-carboxylate (60 mg) as a solid. LCMS (ES, m/z): 487 [M+H] ⁺ . Synthesis of Intermediate C15 To a solution of tert-butyl 4-(6-{4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl}-7-methoxy-1,5 - naphthyridin-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (60 mg, 0.12 mmol, 1 equiv) in 2 mL MeOH was added Pd/C (10%, 120 mg) in a pressure tank. The mixture was hydrogenated at room temperature under 10 psi of hydrogen pressure for 4 h, filtered through a Celite pad, and concentrated under reduced pressure to afford tert-butyl 4-(6-{4,6-dimethylpyrazolo[1,5- a]pyrazin-2-yl}-7-methoxy-1,5-naphthyridin-2-yl)piperidine-1 -carboxylate (30 mg) as a solid. LCMS (ES, m/z): 489 [M+H] ⁺ . A solution of tert-butyl 4-(6-{4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl}-7-methoxy-1,5 - naphthyridin-2-yl)piperidine-1-carboxylate (14 mg, 0.029 mmol, 1 equiv) in DCM (2 mL) and TFA (0.5 mL) was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum to give a residue. The residuewas purified by Prep-HPLC (Condition 9, Gradient 1) to afford 2-{4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl}-3-methoxy-6-(pip eridin-4-yl)-1,5- naphthyridine (1.5 mg, 13%) as a solid. LCMS (ES, m/z): 389 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.57 (s, 1H), 8.35 (d, J = 8.6 Hz, 1H), 7.90 (s, 1H), 7.73 (t, J = 5.7 Hz, 0.2H), 7.62 – 7.53 (m, 2H), 4.11 (s, 3H), 3.13 (d, J = 11.9 Hz, 2H), 3.09 – 2.94 (m, 1H), 2.75 (s, 3H), 2.70 (s, 1H), 2.67 (p, J = 1.8 Hz, 1H), 2.46 – 2.39 (m, 3H), 2.02 (t, J = 7.3 Hz, 0.4H), 1.90 (d, J = 12.7 Hz, 2H), 1.78 (q, J = 12.3 Hz, 2H), 1.46 (q, J = 7.5 Hz, 0.5H), 1.35 (q, J = 7.2 Hz, 0.5H), 1.24 (s, 1.6H), 0.83 (dd, J = 10.6, 6.9 Hz, 0.7H). Example 104: Synthesis of Compounds 299 and 300 Synthesis of Intermediate C16 To a stirred mixture of 2,6-dichloro-1,5-naphthyridine (300 mg, 1.507 mmol, 1 equiv) and 6- (methoxymethoxy)-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)indazole (479.60 mg, 1.507 mmol, 1 equiv) in dioxane (6 mL) and water (1.2 mL) was added Pd(dppf)Cl ₂ CH ₂ Cl ₂ (122.79 mg, 0.151 mmol, 0.1 equiv) and K3PO4 (959.85 mg, 4.521 mmol, 3 equiv) at room temperature under nitrogen atmosphere. The reaction mixture was stirred at 80 °C for 1 hr. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:1) to afford 2-chloro-6-[6- (methoxymethoxy)-2-methylindazol-5-yl]-1,5-naphthyridine (260 mg, 49%) as a solid. Synthesis of Intermediate C17 A mixture of 2-chloro-6-[6-(methoxymethoxy)-2-methylindazol-5-yl]-1,5-nap hthyridine (190 mg, 0.536 mmol, 1 equiv) and tert-butyl N-(pyrrolidin-3-yl)-N-[(1s,3s)-3- fluorocyclobutyl]carbamate (166.02 mg, 0.643 mmol, 1.2 equiv) in DMSO (3.8 mL) was treated with DIEA (207.65 mg, 1.608 mmol, 3 equiv). The reaction mixture was stirred for 4 hr at 100 °C, then cooled to room temperature. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:1) to afford tert-butyl N-(1-{6-[6-(methoxymethoxy)-2-methylindazol-5-yl]-1,5- naphthyridin-2-yl}pyrrolidin-3-yl)-N-[(1s,3s)-3-fluorocyclob utyl]carbamate (90 mg, 29%) as a solid. Synthesis of compounds 299 and 300 A mixture of tert-butyl N-(1-{6-[6-(methoxymethoxy)-2-methylindazol-5-yl]-1,5-naphth yridin - 2-yl}pyrrolidin-3-yl)-N-[(1s,3s)-3-fluorocyclobutyl]carbamat e (90 mg, 0.156 mmol, 1 equiv) and HCl (gas) in 1,4-dioxane (1 mL) in methanol (1 mL) was stirred for 2 h at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-Chiral-HPLC (Condition 4, Gradient 1) to afford 2-methyl-5-{6-[(3S)-3-{[(1s,3s)-3-fluorocyclobutyl]amino}pyr rolidin-1-yl]-1,5- naphthyridin-2-yl}indazol-6-ol (14.3 mg, 21%) as a solid. LCMS (ES, m/z): 433 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 13.λ7 (s, 1H), 8.54 (s, 1H), 8.39 (d, J = 9.1 Hz, 1H), 8.35 (s, 1H), 8.08 (dd, J = 15.9, 9.2 Hz, 2H), 7.14 (d, J = 9.3 Hz, 1H), 6.87 (s, 1H), 4.78 (dt, J = 56.3, 6.9 Hz, 1H), 4.11 (s, 3H), 3.39 (s, 2H), 3.35 (s, 3H), 2.82 – 2.74 (m, 1H), 2.65 (dq, J = 11.6, 5.7, 5.2 Hz, 2H), 2.10 (dq, J = 12.8, 6.4 Hz, 1H), 1.98 – 1.75 (m, 3H). Example 105: Synthesis of Compound 345 Synthesis of Intermediate C18 To a stirred mixture of 2-chloro-6-(6-methoxy-2,7-dimethylindazol-5-yl)-1,7-naphthyr idine (57 mg, 0.16 mmol, 1 equiv) and tert-butyl piperazine-1-carboxylate (47 mg, 0.25 mmol, 1.5 equiv) in DMSO (1 mL) was added DIEA (65.23 mg, 0.50 mmol, 3 equiv) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 100 °C. The reaction mixture was quenched with water at room temperature and extracted with ethyl acetate (2 x 5mL). The organic layers were combined, washed with brine (2 x 5 mL), dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to afford tert-butyl 4-[6-(6-methoxy-2,7-dimethylindazol-5-yl) -1,7-naphthyridin-2- yl]piperazine-1-carboxylate (20 mg, 24%) as a solid. Synthesis of Compound 345 To a stirred mixture of tert-butyl 4-[6-(6-methoxy-2,7-dimethylindazol-5-yl)-1,7-naphthyridin-2 - yl] piperazine-1-carboxylate (20 mg, 0.04 mmol, 1 equiv) in DCE (1 mL) was added BBr ₃ (0.5 mL) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 80°C. The reaction mixture was quenched with methanol at 0 °C. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by Chiral-Prep-HPLC (Condition 10, Gradient 1) to afford 2,7-dimethyl-5-[2-(piperazin-1-yl)-1,7- naphthyridin-6-yl]indazol-6-ol (1.3 mg, 8%) as a solid. LCMS (ES, m/z): 375 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ λ.15 (s, 2H), λ.01 (s, 1H), 8.56 (d, J = 0.9 Hz, 1H), 8.35 (s, 1H), 8.30 – 8.22 (m, 2H), 7.68 (d, J = 9.4 Hz, 1H), 4.14 (s, 3H), 4.02 (t, J = 5.3 Hz, 4H), 3.26 (s, 4H), 2.37 (s, 3H). Example 106: Synthesis of Compound 301 Synthesis of Intermediate C19 To a stirred mixture of 6-chloro-1,7-naphthyridin-2-ol (500 mg, 2.76 mmol, 1 equiv) and 6- methoxy-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborol an-2-yl)indazole (1003.98 mg, 3.32 mmol, 1.2 equiv) in dioxane (5 mL) was added Pd(dppf)Cl ₂ CH ₂ Cl ₂ (225.54 mg, 0.27 mmol, 0.1 equiv), K ₃ PO ₄ (1763.10 mg, 8.307 mmol, 3 equiv), and water (1 mL) at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 80 °C, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ /MeOH (10:1) to afford 6-(6-methoxy-2,7- dimethylindazol-5-yl)-1,7-naphthyridin-2-ol (500 mg, 39%) as a solid. Synthesis of Intermediate C20 To mixture of 6-(6-methoxy-2,7-dimethylindazol-5-yl)-1,7-naphthyridin-2-ol (500 mg, 1.56 mmol, 1 equiv) in phosphorus oxychloride (10 mL) was stirred for 4 h at 80 °C. The resulting mixture was concentrated under vacuum to afford 2-chloro-6-(6-methoxy-2,7-dimethylindazol-5- yl)-1,7-naphthyridine (550 mg, 73%) as a solid. Synthesis of Intermediate C21 To a stirred mixture of 2-chloro-6-(6-methoxy-2,7-dimethylindazol-5-yl)-1,7-naphthyr idine (250 mg, 0.73 mmol, 1 equiv), Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (60.11 mg, 0.07mmol, 0.1 equiv), and CuI (28.11 mg, 0.14 mmol, 0.2 equiv) in DMA (3 mL) was added [1-(tert-butoxycarbonyl)piperidin-4- yl](iodo)zinc (555.70 mg, 1.47 mmol, 2 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 80 °C, then quenched with water at room temperature. The resulting mixture was extracted with ethyl acetate (2 x 5 mL). The combined organic layers were washed with brine (2 x 10 mL), dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to afford tert-butyl 4-[6-(6-methoxy-2,7-dimethylindazol-5-yl)-1,7-naphthyridin-2 -yl]piperidine-1-carboxylate (100 mg, 28%) as a solid. Synthesis of Compound 301 To a stirred solution of tert-butyl 4-[6-(6-methoxy-2,7-dimethylindazol-5-yl)-1,7-naphthyridin-2 - yl] piperidine-1-carboxylate (30 mg, 0.06 mmol, 1 equiv) in DCE (1 mL, 0.01 mmol, 0.16 equiv) was added BBr ₃ (1 mL, 0.004 mmol, 0.06 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 80 °C, then quenched with methanol at 0 °C, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 4, Gradient 4) to afford 2,7- dimethyl-5-[2-(piperidin-4-yl)-1,7-naphthyridin-6-yl]indazol -6-ol (1.4 mg, 6%) as a solid. LCMS (ES, m/z): 374 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 13.30 (s, 1H), λ.41 (d, J = 1.0 Hz, 1H), 8.75 (d, J = 1.0 Hz, 2H), 8.50 – 8.44 (m, 2H), 8.37 (d, J = 2.7 Hz, 2H), 7.81 (d, J = 8.7 Hz, 1H), 4.15 (s, 3H), 3.41(s, 1H), 3.26(s, 2H), 3.12 (d, J = 12.2 Hz, 2H), 2.39 (s, 3H), 2.18 (d, J = 13.6 Hz, 2H), 2.06 (q, J = 11.1 Hz, 2H). Example 107: Synthesis of Compound 283 Synthesis of Intermediate C22 To a stirred mixture of 2-chloro-6-(6-methoxy-2,7-dimethylindazol-5-yl)-1,7-naphthyr idine (250 mg, 0.73 mmol, 1 equiv) and tert-butyl N-methyl-N-(pyrrolidin-3-yl)carbamate (221.68 mg, 1.10 mmol, 1.5 equiv) in DMSO (3 mL) was added DIEA (286.11 mg, 2.21 mmol, 3 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 100 °C. The reaction mixture was quenched with water at room temperature and extracted with ethyl acetate (2 x 5mL). The organic layers were combined, washed with brine (2 x 10 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to afford tert-butyl N-{1-[6-(6-methoxy-2,7- dimethylindazol-5-yl)-1,7-naphthyridin-2-yl] pyrrolidin-3-yl}-N-methylcarbamate (30 mg, 8%) as a solid. Synthesis of Compound 283 To a stirred solution of tert-butyl N-{1-[6-(6-methoxy-2,7-dimethylindazol-5-yl)-1,7- naphthyridin-2-yl] pyrrolidin-3-yl}-N-methylcarbamate (50 mg, 0.099 mmol, 1 equiv) in DCE (1 mL) was added BBr3 (1 mL) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 80 °C, then quenched with methanol at 0 °C, and the resulting mixture was filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 4, Gradient 4) to afford 2,7-dimethyl-5-{2-[3-(methylamino)pyrrolidin-1-yl]-1,7-napht hyridin-6-yl}indazol-6-ol (1 mg, 3%) as a solid. LCMS (ES, m/z): 389 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.78 (s, 1H), 8.90 (s, 1H), 8.48 (s, 1H), 8.29 (s, 1H), 8.22 (s, 1H), 8.12 (d, J = 9.2 Hz, 1H), 7.23 (d, J = 9.2 Hz, 1H), 4.12 (s, 3H), 3.76 – 3.68 (m, 3H), 3.45 (s, 1H), 3.22 (s, 1H), 2.34 (d, J = 12.2 Hz, 3H), 2.30 (s, 3H), 2.12 (dq, J = 13.1, 7.2 Hz, 1H), 1.99 (s, 2H). Example 108: Synthesis of Compound 284, 321, and 322 Synthesis of Intermediate C23 A mixture of tert-butyl N-(cyclopropylmethyl)-N-{1-[6-(trimethylstannyl)-1,5-naphthy ridin-2- yl]pyrrolidin-3-yl}carbamate (600 mg, 1.107 mmol, 1 equiv), 5-bromo-6-(methoxymethoxy)- 2,7-dimethylindazole (316 mg, 1.107 mmol, 1 equiv), Pd(DtBPF)Cl ₂ (72 mg, 0.111 mmol, 0.1 equiv), and K ₃ PO ₄ (705 mg, 3.321 mmol, 3 equiv) in dioxane (10 mL) and water (2 mL) was stirred for 16 hr at 80 °C under nitrogen atmosphere. The reaction mixture was cooled to room temperature, then poured into water (100 mL), and extracted with ethyl acetate (2 x 100 mL). The organic layers were combined, dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:1) to afford tert-butyl N- (cyclopropylmethyl)-N-(1-{6-[6-(methoxymethoxy)-2,7-dimethyl indazol-5-yl]-1,5-naphthyridin- 2-yl}pyrrolidin-3-yl)carbamate (190 mg, 30%) as a solid. LCMS (ES, m/z):573 [M+H] ⁺ . Synthesis of Compound 284 A solution of tert-butyl N-(cyclopropylmethyl)-N-(1-{6-[6-(methoxymethoxy)-2,7- dimethylindazol-5-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl) carbamate (190 mg, 0.332 mmol, 1 equiv) in TFA (1 mL) and DCM (3 mL) was stirred for 1 h at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by Chiral-Prep-HPLC with the following conditions: Column, YMC-Actus Triart C ₁₈ , 30 x 150 mm, 5um; mobile phase, water (10 mmol/L NH ₄ HCO ₃ ) and ACN (30% ACN up to 70% in 8 min); Detector, UV 220 nm) to afford 5-(6-{3-[(cyclopropylmethyl)amino]pyrrolidin-1-yl}-1,5- naphthyridin-2-yl)-2,7-dimethylindazol-6-ol (9.8 mg, 7%) as a solid. LCMS (ES, m/z):429 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.32 (s, 1H), 8.40 (t, J = 4.7 Hz, 2H), 8.33 (s, 1H), 8.14 (d, J = 9.2 Hz, 1H), 8.06 (d, J = 9.1 Hz, 1H), 7.17 (d, J = 9.3 Hz, 1H), 4.13 (s, 3H), 3.77 (dd, J = 10.7, 6.1 Hz, 1H), 3.69 – 3.60 (m, 1H), 3.62 – 3.53 (m, 2H), 3.44 – 3.32 (m, 1H), 2.67 – 2.52(m, 2H), 2.38 (s, 3H), 2.33 – 2.32(m, 1H), 2.00 – 1.93 (s, 1H), 0.91 (dd, J = 12.8, 6.4 Hz, 1H), 0.44 (dt, J = 8.4, 2.9 Hz, 2H), 0.17 (d, J = 4.8 Hz, 2H). 5-(6-{3-[(cyclopropylmethyl)amino]pyrrolidin-1-yl}-1,5-napht hyridin-2-yl)-2,7- dimethylindazol-6-ol was purified by chiral reverse flash chromatography (Condition 1, Gradient 1) to afford (22.3 mg) and (23.7 mg) as solids. Compound 321: LCMS (ES, m/z):429 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.33 (s, 1H), 8.43 – 8.36 (m, 2H), 8.33 (s, 1H), 8.13 (d, J = 9.3 Hz, 1H), 8.06 (d, J = 9.1 Hz, 1H), 7.16 (d, J = 9.3 Hz, 1H), 4.13 (s, 3H), 3.75 (dd, J = 10.8, 5.9 Hz, 1H), 3.68 – 3.60 (m, 1H), 3.57 (d, J = 7.6 Hz, 2H), 3.44 – 3.32 (m, 1H), 2.49 – 2.46 (m, 2H), 2.38 (s, 3H), 2.14 (dd, J = 12.6, 6.3 Hz, 1H), 1.92 – 1.88 (m, 1H), 0.88 (dd, J = 12.8, 6.4 Hz, 1H), 0.46 – 0.37 (m, 2H), 0.18 – 0.10 (m, 2H). Compound 322: LCMS (ES, m/z):429 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 14.33 (s, 1H), 8.40 (t, J = 4.7 Hz, 2H), 8.33 (s, 1H), 8.13 (d, J = 9.2 Hz, 1H), 8.06 (d, J = 9.2 Hz, 1H), 7.16 (d, J = 9.3 Hz, 1H), 4.13 (s, 3H), 3.78 – 3.70 (m, 1H), 3.68 – 3.60 (m, 1H), 3.58 (d, J = 7.6 Hz, 2H), 3.47 (s, 1H), 2.49 – 2.47 (m, 2H), 2.38 (s, 3H), 2.14 (dd, J = 12.6, 6.5 Hz, 1H), 1.88 (s, 1H), 0.89 (dd, J = 12.8, 6.4 Hz, 1H), 0.42 (dt, J = 8.8, 2.8 Hz, 2H), 0.18 – 0.10 (m, 2H). Example 109: Synthesis of Compound 302 4 To a stirred mixture of tert-butyl N-[1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3- yl]carbamate (200 mg, 0.573 mmol, 1 equiv) and Pd(dtbpf)Cl ₂ (37.37 mg, 0.057 mmol, 0.1 equiv) in dioxane (4 mL) was added Sn ₂ Me ₆ (375.69 mg, 1.146 mmol, 2 equiv) dropwise at room temperature under nitrogen atmosphere. The reaction mixture was stirred at 100 °C for 2 hr, then quenched with potassium fluoride solution (10 mL) at room temperature. The resulting mixture was filtered, and the aqueous layer was extracted with ethyl acetate (2 x 10 mL). The organic layers were combined, dried over Na ₂ SO4, filtered, and concentrated under reduced pressure to afford tert-butyl N-{1-[6-(trimethylstannyl)-1,5-naphthyridin-2-yl]pyrrolidin- 3-yl} carbamate (300 mg crude) as an oil. To a stirred mixture of tert-butyl N-{1-[6-(trimethylstannyl)-1,5-naphthyridin-2-yl]pyrrolidin- 3- yl} carbamate (300 mg, 0.629 mmol, 1 equiv) and Pd(dtbpf)Cl ₂ (40.97 mg, 0.063 mmol, 0.1 equiv) in dioxane (6 mL) was added 5-bromo-6-(methoxymethoxy)-2,7-dimethylindazole (215.11 mg, 0.755 mmol, 1.2 equiv) in portions at room temperature under nitrogen atmosphere. The mixture was stirred at 100 °C for 2 hr. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ /MeOH (10:1) to afford tert-butyl N-(1-{6-[6- (methoxymethoxy) -2,7-dimethylindazol-5-yl]-1,5-naphthyridin-2-yl}pyrrolidin- 3-yl)carbamate (150 mg, 46%) as a solid. To a stirred solution of tert-butyl N-(1-{6-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl] -1,5- naphthyridin-2-yl}pyrrolidin-3-yl)carbamate (150 mg, 0.289 mmol, 1 equiv) in methanol (1.5 mL) was added HCl (gas) in 1,4-dioxane (1.5 mL) dropwise at room temperature under nitrogen atmosphere. The mixture was stirred at room temperature for 2 hr. The resulting mixture was concentrated under reduced pressure to afford 5-[6-(3-aminopyrrolidin-1-yl)-1,5-naphthyridin-2- yl]-2,7-dimethylindazol-6-ol (115 mg) as a solid. A solution of 5-[6-(3-aminopyrrolidin-1-yl)-1,5-naphthyridin-2-yl]-2,7-dim ethylindazol-6-ol (90 mg, 0.240 mmol, 1 equiv) in methanol (1.8 mL) was treated with 3-oxetanone (25.98 mg, 0.360 mmol, 1.5 equiv) for 30 min at room temperature under nitrogen atmosphere. To the reaction mixture was added NaBH ₃ CN (45.31 mg, 0.720 mmol, 3 equiv) in portions at room temperature. The resulting mixture was stirred at room temperature for 3 hr, then concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 1, Gradient 15) to afford 2,7-dimethyl-5-{6-[3-(oxetan-3-ylamino)pyrrolidin-1-yl]-1,5- naphthyridin-2-yl}I ndazol- 6-ol (25.9 mg, 25%) as a solid. LCMS (ES, m/z): 431 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 14.33 (s, 1H), 8.43 – 8.36 (m, 2H), 8.33 (s, 1H), 8.12 (d, J = 9.2 Hz, 1H), 8.06 (d, J = 9.1 Hz, 1H), 7.14 (d, J = 9.3 Hz, 1H), 4.67 (td, J = 6.5, 2.8 Hz, 2H), 4.36 (dt, J = 8.7, 6.2 Hz, 2H), 4.13 (s, 3H), 4.00 (d, J = 7.2 Hz, 1H), 3.69 (dd, J = 10.9, 5.9 Hz, 2H), 3.55 (s, 1H), 3.35 (s, 1H), 2.80 (s, 1H), 2.38 (s, 3H), 2.13 – 2.01 (m, 1H), 1.79 (dd, J = 12.6, 6.5 Hz, 1H). Example 110: Synthesis of Compounds 315-317 27 A mixture of tert-butyl N-[1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3-yl]-N- cyclobutylcarbamate (400 mg, 0.993 mmol, 1 equiv), 7-fluoro-6-(methoxymethoxy)-2-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazole (834 mg, 2.482 mmol, 2.5 equiv), K3PO4 (632 mg, 2.979 mmol, 3 equiv), and Pd(DtBPF)Cl ₂ (65 mg, 0.099 mmol, 0.1 equiv) in 1,4- dioxane (6.7 mL) and water (1.3 mL) was stirred for 16 hr at 80 °C under nitrogen atmosphere. The reaction mixture was cooled to room temperature, then extracted with ethyl acetate (1 x 40 mL). The organic layers were combined, dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:1), followed by Prep-HPLC (Condition 2, Gradient 10) to afford tert-butyl N-cyclobutyl-N-(1-{6-[7-fluoro-6- (methoxymethoxy)-2-methylindazol-5-yl]-1,5-naphthyridin-2-yl }pyrrolidin-3-yl)carbamate (158 mg, 28%) as a solid. LCMS (ES, m/z): 577 [M+H] ⁺ . 315 A mixture of tert-butyl N-cyclobutyl-N-(1-{6-[7-fluoro-6-(methoxymethoxy)-2-methylin dazol- 5-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl)carbamate (28 mg, 0.049 mmol, 1 equiv) in methanol (1 mL) and HCl (gas) in 1,4-dioxane (1 mL) was stirred for 1 h at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 3, Gradient 21) to afford 5-{6-[3- (cyclobutylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2-yl}-7-f luoro-2-methylindazol-6-ol (5.6 mg, 26%) as a solid. LCMS (ES, m/z): 433 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.44 (s, 1H), 8.48 (d, J = 2.7 Hz, 1H), 8.45 – 8.38 (m, 2H), 8.14 (d, J = 22.9, 9.2 Hz, 1H), 8.08 (d, J = 22.9, 9.2 Hz, 1H),7.16 (d, J = 9.3 Hz, 1H), 4.16 (s, 3H), 3.69 (s, 2H), 3.56 (s, 1H), 3.40 (s, 1H), 3.26 (s, 2H),2.14 (s, 3H), 1.83 (s, 1H), 1.71 (s, 2H), 1.59 (d, J = 18.6, 9.3, 8.3 Hz, 2H). Synthesis of Intermediates C28 and C29 5-{6-[3-(cyclobutylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2 -yl}-7-fluoro-2-methylindazol-6-ol was purified by Prep-HPLC (Column: CHIRAL ART Cellulose-SB, 2X25 cm, 5 μm; Mobile Phase A: MtBE(0.1% DEA)-HPLC, Mobile Phase B: MeOH--HPLC; Flow rate: 20 mL/min; Gradient: 30% B to 30% B in 6.5 min; Wave Length: 220/254 nm; RT1(min): 5.1; RT2(min): 5.9; Sample Solvent: MeOH: DCM=8: 1; Injection Volume: 0.3 mL; Number Of Runs: 32) to afford (First peak) (59 mg) and (Second peak)(63 mg) as solids.LCMS: (ES, m/z): 577 [M+H] ⁺ . Synthesis of Compound 316 A mixture of tert-butyl N-cyclobutyl-N-[(3R)-1-{6-[7-fluoro-6-(methoxymethoxy)-2- methylindazol-5-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl]ca rbamate (59 mg, 0.102 mmol, 1 equiv) in DCM (2 mL) and TFA (1 mL) was stirred for 1 hr at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 3, Gradient 20) to afford Compound 316 (26 mg, 58%) as a solid. LCMS (ES, m/z): 433 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 14.44 (s, 1H), 8.48 (d, J = 2.7 Hz, 1H), 8.44 – 8.38 (m, 2H), 8.14 (d, J = 9.4 Hz, 1H), 8.08 (d, J = 9.1 Hz, 1H), 7.16 (d, J = 9.3 Hz, 1H), 4.16 (s, 3H), 3.69 (s, 2H), 3.56 (s, 1H), 3.38 (m, 1H), 3.27 (m, 1H),2.12 (ddd, J = 18.2, 9.3, 4.9 Hz, 4H), 1.83 (s, 1H), 1.70 (dd, J = 11.4, 8.2 Hz, 2H), 1.64 – 1.50 (m, 2H). Synthesis of Compound 317 A mixture of tert-butyl N-cyclobutyl-N-[(3S)-1-{6-[7-fluoro-6-(methoxymethoxy)-2- methylindazol-5-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl]ca rbamate (63 mg, 0.109 mmol, 1 equiv) in DCM (2 mL) and TFA (1 mL) was stirred for 1 h at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 3, Gradient 20) to afford Compound 317 (26 mg, 55%) as a solid. LCMS (ES, m/z): 433 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 14.44 (s, 1H), 8.48 (d, J = 2.6 Hz, 1H), 8.44 – 8.38 (m, 2H), 8.11 (d, J = 22.0, 9.3 Hz, H), 8.08 (d, J = 9.1 Hz, 1H), 7.16 (d, J = 9.3 Hz, 1H), 4.16 (s, 3H), 3.69 (s, 2H), 3.56 (s, 1H), 3.38 (m, 1H), 3.27 (m, 1H),2.12 (ddt, J = 18.1, 11.9, 5.1 Hz, 4H), 1.82 (s, 1H), 1.69 (m, 2H), 1.58 (m, 2H). Example 111: Synthesis of Compounds 294, 303, and 304 Synthesis of Intermediate C29 A mixture of tert-butyl N-[1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3-yl]-N- (cyclopropylmethyl)carbamate (500 mg, 1.241 mmol, 1 equiv), 7-fluoro-6-methoxy-2-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazole (380 mg, 1.241 mmol, 1 equiv), Pd(DtBPF)Cl ₂ (81 mg, 0.124 mmol, 0.1 equiv), and K3PO4 (790 mg, 3.723 mmol, 3 equiv) in dioxane (10 mL) and water (2 mL) was stirred for 16 h at 80 °C under nitrogen atmosphere. The reaction mixture cooled to room temperature, poured into water (20 mL), and extracted with ethyl acetate (3 x 20 mL). The organic layers were combined, dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:1) to afford tert-butyl N-(cyclopropylmethyl)-N-{1-[6-(7-fluoro-6-methoxy-2-methylin dazol-5-yl)-1,5- naphthyridin-2-yl]pyrrolidin-3-yl}carbamate (300 mg, 44%) as a solid. LCMS (ES, m/z):547 [M+H] ⁺ . Synthesis of Compound 294 To a stirred solution of tert-butyl N-(cyclopropylmethyl)-N-{1-[6-(7-fluoro-6-methoxy-2- methylindazol-5-yl)-1,5-naphthyridin-2-yl]pyrrolidin-3-yl}ca rbamate (300 mg, 0.549 mmol, 1 equiv) in DCM (6 mL) was added BBr ₃ (687 mg, 2.745 mmol, 5 equiv) dropwise at 0 °C. The resulting mixture was stirred for 16 h at room temperature. The reaction mixture was quenched with methanol (30 mL) at 0 °C, then concentrated under reduced pressure and basified to pH 8 with saturated NaHCO ₃ (aq.). The resulting mixture was extracted with CH ₂ Cl ₂ (3 x 50 mL). The organic layers were combined, dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 3, Gradient 22) to afford 5-(6-{3-[(cyclopropylmethyl)amino]pyrrolidin- 1-yl}-1,5-naphthyridin-2-yl)-7-fluoro-2-methylindazol-6-ol (75 mg) as a solid. LCMS (ES, m/z):433 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 14.44 (s, 1H), 8.48 (d, J = 2.7 Hz, 1H), 8.44 – 8.37 (m, 2H), 8.14 (dd, J = 9.3, 0.8 Hz, 1H), 8.11 – 8.05 (m, 1H), 7.17 (d, J = 9.3 Hz, 1H), 4.16 (s, 3H), 3.82 – 3.68 (m, 3H), 3.57 (d, J = 8.8 Hz, 1H), 3.45 (t, J = 5.4 Hz, 1H), 2.46 (d, J = 6.6 Hz, 2H), 2.13 (dq, J = 12.9, 6.6 Hz, 1H), 1.88 (dd, J = 12.3, 6.2 Hz, 2H), 0.96 – 0.82 (m, 1H), 0.46 – 0.35 (m, 2H), 0.17 – 0.05 (m, 2H). Synthesis of Compounds 303 and 304 5-(6-{3-[(cyclopropylmethyl)amino]pyrrolidin-1-yl}-1,5-napht hyridin-2-yl)-7-fluoro-2- methylindazol-6-ol was purified by chiral prep-HPLC (CHIRAL ART Cellulose-SB, 2 x 25 cm, 5 um; Mobile Phase A: MtBE (0.1% DEA)-HPLC, Mobile Phase B: MeOH--HPLC; Flow rate: 20 mL/min; Gradient: 28% B to 28% B in 7 min; Wave Length: UV 220/254 nm; RT1(min): 6.1; RT2(min): 6.7; Sample Solvent: MeOH: DCM=1: 2; Injection Volume: 0.24 mL; Number Of Runs: 28) to afford the compounds as solids. Compound 303: LCMS (ES, m/z):433 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.44 (s, 1H), 8.48 (d, J = 2.7 Hz, 1H), 8.44 – 8.37 (m, 2H), 8.11 (dd, J = 21.8, 9.2 Hz, 2H), 7.17 (d, J = 9.3 Hz, 1H), 4.16 (s, 3H), 3.74 (dd, J = 10.8, 5.8 Hz, 1H), 3.68 (s, 1H), 3.58 (s, 1H), 3.48 – 3.41 (m, 2H), 2.46 (d, J = 6.7 Hz, 2H), 2.13 (dq, J = 12.9, 6.7 Hz, 1H), 1.97 (s, 1H), 1.91 – 1.83 (m, 1H), 0.96 – 0.82 (m, 1H), 0.46 – 0.35 (m, 2H), 0.17 – 0.09 (m, 2H). Compound 304: LCMS (ES, m/z):433 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.44 (s, 1H), 8.48 (d, J = 2.7 Hz, 1H), 8.45 – 8.38 (m, 2H), 8.15 (d, J = 9.3 Hz, 1H), 8.09 (d, J = 9.1 Hz, 1H), 7.18 (d, J = 9.3 Hz, 1H), 4.16 (s, 3H), 3.74 (d, J = 7.5 Hz, 1H), 3.69 (s, 1H), 3.49 (s, 1H), 3.58 (s, 1H), 3.48 – 3.41 (m, 2H), 2.46 (d, J = 6.7 Hz, 2H), 2.15 (dd, J = 12.4, 6.4 Hz, 1H), 1.90 (s, 1H), 0.89 (s, 1H), 0.42 (dt, J = 8.4, 2.8 Hz, 2H), 0.19 – 0.11 (m, 2H). Example 112: Synthesis of Compounds 285, 286, and 388 Synthesis of Compound 388 A mixture of 5-[6-(3-aminopyrrolidin-1-yl)-1,5-naphthyridin-2-yl]-7-fluor o-2-methylindazol-6- ol (280 mg, 0.74 mmol, 1.00 equiv), acetone (85.95 mg, 1.48 mmol, 2.00 equiv), AcOH (4.44 mg, 0.07 mmol, 0.10 equiv), and methanol (20 mL) was stirred for 2 h at room temperature under nitrogen atmosphere. To the reaction mixture was added NaBH ₃ CN (232.50 mg, 3.70 mmol, 5.00 equiv) dropwise at 0 °C. The resulting mixture was stirred for 2 hr at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 3, Gradient 16) to afford 7-fluoro-5-{6-[3-(isopropylamino) pyrrolidin-1-yl]-1,5-naphthyridin-2-yl}-2-methylindazol-6-ol (65 mg, 21%) as a solid. LCMS (ES, m/z):421 [M+H] ⁺ . Synthesis of Compound 285 7-fluoro-5-{6-[3-(isopropylamino)pyrrolidin-1-yl]-1,5-naphth yridin-2-yl}-2-methylindazol-6-ol (65 mg, 0.155 mmol, 1 equiv) was purified by reverse flash chromatography (column, CHIRAL ART Cellulose-SB, 4.6*100 mm, 3μm; Mobile Phase Aμ MtBE(0.1%DEA)μ MeOH=70μ 30; Flow rate: 1 mL/min) to afford 7-fluoro-5-{6-[(3R)-3-(isopropylamino) pyrrolidin-1-yl]-1,5- naphthyridin-2-yl}-2-methylindazol-6-ol (27 mg, 41%) as a solid. LCMS (ES, m/z):421 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.44 (s, 1H), 8.48 (d, J = 2.7 Hz, 1H), 8.44 – 8.38 (m, 2H), 8.11 (dd, J = 22.1, 9.2 Hz, 2H), 7.17 (d, J = 9.3 Hz, 1H), 4.16 (s, 2H), 3.80 (s, 1H), 3.71 (s, 1H), 3.55 (d, J = 9.9 Hz, 2H), 2.88 (s, 1H), 2.48 (s, 5H), 2.16 (s, 1H), 1.82 (s, 1H), 1.03 (dd, J = 6.2, 4.5 Hz, 5H). Synthesis of Compound 286 7-fluoro-5-{6-[3-(isopropylamino)pyrrolidin-1-yl]-1,5-naphth yridin-2-yl}-2-methylindazol-6-ol (65 mg, 0.155 mmol, 1 equiv) was purified by chiral reverse flash chromatography (column, CHIRAL ART Cellulose-SB, 4.6*100 mm, 3μm; Mobile Phase Aμ MtBE (0.1%DEA)μ MeOH=70: 30; Flow rate: 1 mL/min) to afford 7-fluoro-5-{6-[(3S)-3- (isopropylamino)pyrrolidin-1-yl] -1,5-naphthyridin-2-yl}-2-methylindazol-6-ol (27.1 mg, 41%) as a solid. LCMS (ES, m/z):421 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 14.44 (s, 1H), 8.48 (d, J = 2.7 Hz, 1H), 8.44 – 8.38 (m, 2H), 8.14 (d, J = 9.2 Hz, 1H), 8.08 (d, J = 9.1 Hz, 1H), 7.17 (d, J = 9.3 Hz, 1H), 4.16 (s, 3H), 3.81 (s, 1H), 3.71 (s, 1H), 3.55 (dd, J = 11.8, 5.3 Hz, 2H), 3.21 (s, 1H), 2.91 (s, 1H), 2.18 (q, J = 6.8 Hz, 1H), 1.84 (s, 1H), 1.04 (dd, J = 6.2, 4.4 Hz, 6H). Example 113: Synthesis of Compound 389, 451, and 452 Synthesis of Intermediate C30 A mixture of tert-butyl N-[1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3-yl]-N- (cyclopropylmethyl)carbamate (500 mg, 1.241 mmol, 1 equiv), 5-(methoxymethoxy)-2-methyl- 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxaz ole (396 mg, 1.241 mmol, 1.00 equiv), Pd(DtBPF)Cl ₂ (81 mg, 0.124 mmol, 0.1 equiv), and K ₃ PO ₄ (790 mg, 3.723 mmol, 3 equiv) in dioxane (10 mL) and water (2 mL) was stirred for 16 hr at 80 °C under nitrogen atmosphere. The resulting mixture was cooled to room temperature, then poured into water (20 mL), extracted with ethyl acetate (3 x 20 mL), dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:1) to afford tert-butyl N- (cyclopropylmethyl)-N-(1-{6-[5-(methoxymethoxy)-2-methyl-1,3 -benzoxazol-6-yl]-1,5- naphthyridin-2-yl}pyrrolidin-3-yl)carbamate (350 mg, 50%) as a solid. LCMS (ES, m/z):560 [M+H] ⁺ . Synthesis of Compound 389 A mixture of tert-butyl N-(cyclopropylmethyl)-N-(1-{6-[5-(methoxymethoxy)-2-methyl-1 ,3- benzoxazol-6-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl)carba mate (350 mg, 0.625 mmol, 1 equiv) and HCl (gas) in 1,4-dioxane (1 mL) and methanol (2 mL) was stirred for 1 h at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 2, Gradient 12) to afford 6-(6-{3- [(cyclopropylmethyl)amino]pyrrolidin-1-yl}-1,5-naphthyridin- 2-yl)-2-methyl-1,3-benzoxazol-5- ol (110 mg) as a solid. LCMS (ES, m/z):416 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.53 (s, 1H), 8.45 – 8.39 (m, 2H), 8.10 (dd, J = 15.2, 9.2 Hz, 2H), 7.16 (d, J = 9.3 Hz, 1H), 7.12 (s, 1H), 3.74 (dd, J = 10.8, 5.9 Hz, 1H), 3.68 (s, 1H), 3.58 (s, 1H), 3.48 – 3.41 (m, 1H), 2.61 (s, 3H), 2.46 (d, J = 6.7 Hz, 2H), 2.13 (dq, J = 12.8, 6.6 Hz, 1H), 1.88 – 1.85 (m, 2H), 0.96 – 0.82 (m, 1H), 0.45 – 0.37 (m, 2H), 0.17 – 0.05 (m, 2H). Synthesis of Compounds 451 and 452 6-(6-{3-[(cyclopropylmethyl)amino]pyrrolidin-1-yl}-1,5-napht hyridin-2-yl)-2-methyl-1,3- benzoxazol-5-ol (90 mg, 0.217 mmol, 1 equiv) was purified by chiral prep-HPLC (Condition 4, Gradient 1) to afford Compound 451 (First peak) (17.7 mg) and Compound 452 (Second peak) (18.5 mg) as solids. Compound 451: LCMS (ES, m/z):416 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.53 (s, 1H), 8.46 – 8.39 (m, 2H), 8.11 (dd, J = 17.2, 9.2 Hz, 2H), 7.17 (d, J = 9.3 Hz, 1H), 7.12 (s, 1H), 3.75 (dd, J = 9.9, 5.4 Hz, 1H), 3.68 (s, 1H), 3.58 (d, J = 8.0 Hz, 1H), 3.57 – 3.48 (m, 1H), 3.47 – 3.38 (m, 1H), 2.61 (s, 3H), 2.48 (s, 2H), 2.20 – 2.10 (m, 1H), 1.89 – 1.88 (m, 1H), 0.95 – 0.85 (m, 1H), 0.47 – 0.38 (m, 2H), 0.19 – 0.10 (m, 2H). Compound 452: LCMS (ES, m/z):416 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.54 (s, 1H), 8.46 – 8.39 (m, 2H), 8.16 – 8.05 (m, 2H), 7.17 (d, J = 9.3 Hz, 1H), 7.12 (s, 1H), 3.78 – 3.66 (m, 2H), 3.58 (d, J = 8.0 Hz, 1H), 3.57 – 3.48 (m, 1H), 3.47 – 3.38 (m, 1H), 2.61 (s, 3H), 2.47 (d, J = 6.4 Hz, 2H), 2.14 (dd, J = 12.5, 6.3 Hz, 1H), 1.89 – 1.88 (m, 1H), 0.94 – 0.84 (m, 1H), 0.46 – 0.37 (m, 2H), 0.18 – 0.10 (m, 2H). Example 114: Synthesis of Compound 293, 307, and 308 Synthesis of Intermediate C31 A mixture of 6-bromo-4-fluoro-5-(methoxymethoxy)-2-methyl-1,3-benzoxazole (250 mg, 0.862 mmol, 1 equiv), tert-butyl N-cyclobutyl-N-{1-[6-(trimethylstannyl)-1,5-naphthyridin-2-y l] pyrrolidin-3-yl} carbamate (687 mg, 1.293 mmol, 1.5 equiv), and Pd(DtBPF)Cl ₂ (56 mg, 0.086 mmol, 0.1 equiv) in 1,4-dioxane (2.5 mL) was stirred for 2 hr at 100 °C under nitrogen atmosphere. The reaction mixture was cooled to room temperature, then poured into the water (10 mL), extracted with ethyl acetate (1 x 10 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:1) to afford tert-butyl N-cyclobutyl-N-(1-{6-[4-fluoro-5-(methoxymethoxy)-2-methyl-1 ,3-benzoxazol-6-yl]- 1,5-naphthyridin-2-yl}pyrrolidin-3-yl)carbamate (200 mg, 40%) as a solid. LCMS (ES, m/z): 578 [M+H] ⁺ . Synthesis of Compound 293 A mixture of tert-butyl N-cyclobutyl-N-(1-{6-[4-fluoro-5-(methoxymethoxy)-2-methyl-1 ,3- benzoxazol-6-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl)carba mate (200 mg, 0.346 mmol, 1 equiv) in DCM (2 mL) and CF ₃ COOH (1 mL) was stirred for 1 hr at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by (Condition 3, Gradient 23) to afford 6-{6-[3-(cyclobutylamino)pyrrolidin-1-yl]-1,5- naphthyridin-2-yl}-4-fluoro-2-methyl-1,3-benzoxazol-5-ol (12 mg, 8%) as a solid. LCMS (ES, m/z): 434 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 15.08 (s, 1H), 8.45 (d, J = 9.3 Hz, 1H), 8.34 (d, J = 1.4 Hz, 1H), 8.17 (d, J = 9.3 Hz, 1H), 8.11 (d, J = 9.2 Hz, 2H), 7.18 (d, J = 9.3 Hz, 1H), 3.69 (s, 2H), 3.55 (s, 1H), 3.37 (s, 1H), 3.29 (s, 2H),2.64 (s, 3H), 2.18 – 2.06 (m, 4H), 1.83 (s, 1H), 1.74 – 1.63 (m, 2H), 1.63 – 1.50 (m, 2H). Synthesis of Compounds 307 and 308 6-{6-[3-(cyclobutylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2 -yl}-4-fluoro-2-methyl-1,3- benzoxazol-5-ol was purified by chiral prep-HPLC (Column: CHIRAL ART Cellulose-SB, 2X25 cm, 5 μm; Mobile Phase Aμ MtBE(0.1% DEA)-HPLC, Mobile Phase B: MeOH--HPLC; Flow rate: 20 mL/min; Gradient: 30% B to 30% B in 7.5 min) to afford Compound 307 (First peak) (32 mg, 41%) and Compound 308 (30.5 mg, 39%) as solids. Compound 307: LCMS (ES, m/z): 434 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 15.08 (s, 1H), 8.45 (d, J = 9.2 Hz, 1H), 8.34 (d, J = 1.4 Hz, 1H), 8.14 (d, J = 22.3, 9.3 Hz, 1H), 8.08 (d, J = 22.3, 9.3 Hz, 1H), 7.18 (d, J = 9.3 Hz, 1H), 3.70 (s, 2H), 3.56 (s, 1H), 3.36 (s, 1H), 3.25 (s, 2H),2.64 (s, 3H), 2.18 – 2.05 (m, 4H), 1.83 (s, 1H), 1.70 (t, J = 9.8 Hz, 2H), 1.66 – 1.50 (m, 2H). Compound 308: LCMS (ES, m/z): 434 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 15.08 (s, 1H), 8.45 (d, J = 9.2 Hz, 1H), 8.34 (d, J = 1.4 Hz, 1H), 8.17 (d, J = 9.3 Hz, 1H), 8.11 (d, J = 9.1 Hz, 1H), 7.18 (d, J = 9.3 Hz, 1H), 3.70 (s, 2H), 3.56 (s, 1H), 3.36 (s, 1H), 3.25 (s, 2H),2.64 (s, 3H), 2.18 – 2.10 (m, 4H), 1.83 (s, 1H), 1.70 (s, 2H), 1.57 (dt, J = 18.4, 8.8 Hz, 2H). Example 115: Synthesis of Compound 294, 323, and 324 Synthesis of Intermediate C32 A mixture of tert-butyl N-(cyclopropylmethyl)-N-{1-[6-(trimethylstannyl)-1,5-naphthy ridin -2- yl]pyrrolidin-3-yl}carbamate (600 mg, 1.129 mmol, 1 equiv), 6-bromo-4-fluoro-5- (methoxymethoxy) -2-methyl-1,3-benzoxazole (328 mg, 1.129 mmol, 1 equiv), Pd(DtBPF)Cl ₂ (74 mg, 0.113 mmol, 0.1 equiv), and K ₃ PO ₄ (719 mg, 3.387 mmol, 3 equiv) in dioxane (10 mL) and water (2 mL) was stirred for 16 hr at 80 °C under nitrogen atmosphere. The reaction mixture was cooled to room temperature, then poured into water (100 mL), extracted with ethyl acetate (2 x 100 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:1) to afford tert-butyl N-(cyclopropylmethyl)-N- (1-{6-[4-fluoro-5-(methoxymethoxy)-2-methyl-1,3-benzoxazol-6 -yl]-1,5-naphthyridin-2- yl}pyrrolidin-3-yl)carbamate (290 mg, 44%) as a solid. LCMS (ES, m/z):578 [M+H] ⁺ . Synthesis of Compound 294 A solution of tert-butyl N-(cyclopropylmethyl)-N-(1-{6-[4-fluoro-5-(methoxymethoxy) -2- methyl-1,3-benzoxazol-6-yl]-1,5-naphthyridin-2-yl}pyrrolidin -3-yl)carbamate (290 mg, 0.502 mmol, 1 equiv) in TFA (1 mL) and DCM (3 mL) was stirred for 1 h at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (Condition 3, Gradient 24) to afford 6-(6-{3- [(cyclopropylmethyl)amino]pyrrolidin-1-yl}-1,5-naphthyridin- 2-yl)-4-fluoro-2-methyl-1,3- benzoxazol-5-ol (12.4 mg, 5%) as a solid. LCMS (ES, m/z):434 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 15.08 (s, 1H), 8.45 (d, J = 9.3 Hz, 1H), 8.33 (d, J = 1.4 Hz, 1H), 8.17 (d, J = 9.4 Hz, 1H), 8.11 (d, J = 9.1 Hz, 1H), 7.19 (d, J = 9.3 Hz, 1H), 3.74 (d, J = 10.4 Hz, 1H), 3.69 – 3.58 (m, 1H), 3.58 – 3.47 (m, 2H), 3.47 – 3.40 (m, 1H), 2.64 (s, 3H), 2.47 (d, J = 6.6 Hz, 2H), 2.14 (dd, J = 12.6, 6.2 Hz, 1H), 1.93 – 1.89 (m, 1H), 0.95 – 0.84 (m, 1H), 0.46 – 0.37 (m, 2H), 0.18 – 0.10 (m, 2H). Synthesis of Compounds 323 and 324 6-(6-{3-[(cyclopropylmethyl)amino]pyrrolidin-1-yl}-1,5-napht hyridin-2-yl)-4-fluoro-2-methyl- 1,3-benzoxazol-5-ol was purified by chiral reverse flash chromatography (Condition 1, Gradient 2) to afford (25.9 mg) and (25.9 mg) as solids. Compound 323: LCMS (ES, m/z):434 [M+H] ⁺ . 1H NMR (400 MHz, DMSO-d6) δ 15.07 (s, 1H), 8.43 (dd, J = 9.3, 1.6 Hz, 1H), 8.32 (d, J = 1.8 Hz, 1H), 8.16 (dd, J = 9.4, 1.7 Hz, 1H), 8.11 (d, J = 9.0 Hz, 1H), 7.18 (dd, J = 9.4, 1.5 Hz, 1H), 3.79 – 3.66 (m, 2H), 3.58 – 3.47 (m, 2H), 3.47 (t, J = 5.5 Hz, 1H), 2.64 (s, 3H), 2.47 (d, J = 6.6 Hz, 2H), 2.14 (dq, J = 12.9, 6.5 Hz, 1H), 1.93 – 1.85 (m, 1H), 0.95 – 0.84 (m, 1H), 0.46 – 0.36 (m, 2H), 0.18 – 0.10 (m, 2H). (second peak): LCMS (ES, m/z):434 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 15.07 (s, 1H), 8.45 (d, J = 9.2 Hz, 1H), 8.33 (d, J = 1.5 Hz, 1H), 8.17 (d, J = 9.3 Hz, 1H), 8.14 – 8.08 (m, 1H), 7.19 (d, J = 9.3 Hz, 1H), 3.77 – 3.66 (m, 2H), 3.59 – 3.46 (m, 2H), 3.46 – 3.40 (d, J = 6.5 Hz, 1H), 2.64 (s, 3H), 2.47 (d, J = 6.5 Hz, 2H), 2.14 (dd, J = 12.5, 6.4 Hz, 1H), 1.93 – 1.85 (m, 1H), 0.89 (dtd, J = 12.3, 6.8, 5.8, 4.1 Hz, 1H), 0.46 – 0.37 (m, 2H), 0.18 – 0.10 (m, 2H). Example 116: Synthesis of Compound 325, 326, and 327 Synthesis of Intermediate C33 To a stirred mixture of tert-butyl N-[1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3-yl] -N-(1- methylcyclopropyl)carbamate (500 mg, 1.241 mmol, 1 equiv) and Pd(DtBPF)Cl ₂ (80.88 mg, 0.124 mmol, 0.1 equiv) in dioxane (15 mL) was added Sn ₂ Me ₆ (609.85 mg, 1.862 mmol, 1.5 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 hr at 100 °C, then quenched with of a potassium fluoride solution (10 mL) at room temperature. The resulting mixture was extracted with ethyl acetate (2 x 50 mL). The organic layers were combined, washed with brine (2 x 50 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to afford tert-butyl N-(1-methylcyclopropyl)-N-{1-[6-(trimethylstannyl)-1,5-napht hyridin -2-yl]pyrrolidin-3- yl}carbamate (800 mg, 85%) as an oil. Synthesis of Intermediate C34 To a stirred mixture of tert-butyl N-(1-methylcyclopropyl)-N-{1-[6-(trimethylstannyl)-1,5- naphthyridin -2-yl]pyrrolidin-3-yl}carbamate (700 mg, 1.318 mmol, 1 equiv) and 6-bromo-4- fluoro-5-(methoxymethoxy)-2-methyl-1,3-benzoxazole (458.65 mg, 1.582 mmol, 1.2 equiv) in dioxane (35 mL) was added Pd(dtbpf)Cl ₂ at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 100 °C, then filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ /MeOH (10:1) to afford tert-butyl N-(1-{6-[4- fluoro-5-(methoxymethoxy)-2-methyl-1,3-benzoxazol-6-yl]-1,5- naphthyridin-2-yl}pyrrolidin-3- yl)-N-(1-methylcyclopropyl)carbamate (350 mg, 46%) as a solid. Synthesis of Compound 325 To a stirred solution of tert-butyl N-(1-{6-[4-fluoro-5-(methoxymethoxy)-2-methyl-1,3- benzoxazol-6-yl]-1,5-naphthyridin-2-yl} pyrrolidin-3-yl)-N-(1-methylcyclopropyl) carbamate (320 mg, 0.554 mmol, 1 equiv) in methanol (4 mL) was added HCl (gas) in 1,4-dioxane (4 mL) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 hr at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (Condition 2, Gradient 12) to afford 4-fluoro-2-methyl-6-(6- {3-[(1-methylcyclopropyl)amino]pyrrolidin-1-yl}-1,5-naphthyr idin-2-yl)-1,3-benzoxazol-5-ol (10.9 mg, 5%) as a solid. LCMS (ES, m/z): 434 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 15.08 (s, 1H), 8.44 (d, J = 9.2 Hz, 1H), 8.33 (d, J = 1.4 Hz, 1H), 8.16-8.11 (d, J = 9.4 Hz, 2H), 7.18 (d, J = 9.3 Hz, 1H), 3.78 (s, 1H), 3.66 (s, 2H), 3.54 (d, J = 9.0 Hz, 1H), 3.54 (d,1H), 2.64 (s, 3H), 2.17 – 2.10 (m, 1H), 1.85 (s, 1H), 1.27 (s, 3H), 0.49 (q, J = 10.9, 10.1 Hz, 2H), 0.35 (s, 2H). Synthesis of Compounds 326 and 327 4-fluoro-2-methyl-6-(6-{3-[(1-methylcyclopropyl)amino]pyrrol idin-1-yl}-1,5-naphthyridin-2- yl)-1,3-benzoxazol-5-ol was purified by chiral prep-HPLC (Condition 4, Gradient 3) to afford 4- fluoro-2-methyl-6-{6-[(3S)-3-[(1-methylcyclopropyl)amino]pyr rolidin-1-yl]-1,5-naphthyridin-2- yl}-1,3-benzoxazol-5-ol (15.7 mg, 7%) and 4-fluoro-2-methyl-6-{6-[(3R)-3-[(1- methylcyclopropyl) amino] pyrrolidin-1-yl]-1,5-naphthyridin-2-yl}-1,3-benzoxazol-5-ol (15.8 mg, 7%) as solids. Compound 326: LCMS (ES, m/z): 434 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 15.08 (s, 1H), 8.44 (d, J = 9.2 Hz, 1H), 8.33 (d, J = 1.4 Hz, 1H), 8.16-8.11 (d, J = 9.4 Hz, 2H), 7.18 (d, J = 9.3 Hz, 1H), 3.78 (s, 1H), 3.66 (s, 2H), 3.54 (d, J = 9.0 Hz, 1H), 3.54 (d,1H), 2.64 (s, 3H), 2.17 – 2.10 (m, 1H), 1.85 (s, 1H), 1.27 (s, 3H), 0.49 (q, J = 10.9, 10.1 Hz, 2H), 0.35 (s, 2H). Compound 327: LCMS (ES, m/z): 434 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 15.08 (s, 1H), 8.44 (d, J = 9.2 Hz, 1H), 8.33 (d, J = 1.4 Hz, 1H), 8.16-8.11 (d, J = 9.4 Hz, 2H), 7.18 (d, J = 9.3 Hz, 1H), 3.78 (s, 1H), 3.66 (s, 2H), 3.54 (d, J = 9.0 Hz, 1H), 3.54 (d,1H), 2.64 (s, 3H), 2.17 – 2.10 (m, 1H), 1.85 (s, 1H), 1.27 (s, 3H), 0.49 (q, J = 10.9, 10.1 Hz, 2H), 0.35 (s, 2H). Example 117: Synthesis of Compounds 309, 310, and 311 Synthesis of Intermediate C35

To a stirred mixture of tert-butyl N-[1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3-yl]-N-(1- methylcyclopropyl)carbamate (500 mg, 1.241 mmol, 1 equiv), 5-methoxy-2,4-dimethyl-6- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol e (395.03 mg, 1.303 mmol, 1.05 equiv), and Pd(dppf)Cl ₂ (101.09 mg, 0.124 mmol, 0.1 equiv) in 1,4-dioxane (10 mL) was added K3PO4 (790.23 mg, 3.723 mmol, 3 equiv) in water (2 mL) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 hr at 100 °C under nitrogen atmosphere. The resulting mixture was cooled to room temperature, then diluted with water (30 mL) and extracted with CH ₂ Cl ₂ (3 x 30 mL). The organic layers were combined, washed with brine (1 x 30 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (2:1) to afford tert-butyl N-{1-[6-(5-methoxy-2,4- dimethyl-1,3-benzoxazol-6-yl)-1,5-naphthyridin-2-yl]pyrrolid in-3-yl}-N-(1- methylcyclopropyl)carbamate (600 mg, 89%) as a solid. LCMS (ESI, m/z): 544[M+H]. Synthesis of Compound 309 To a stirred solution of tert-butyl N-{1-[6-(5-methoxy-2,4-dimethyl-1,3-benzoxazol-6-yl)- 1,5- naphthyridin-2-yl] pyrrolidin-3-yl}-N-(1-methylcyclopropyl)carbamate (600 mg, 1.104 mmol, 1 equiv) in DCM (30 mL) was added BBr3 (2764.81 mg, 11.040 mmol, 10 equiv) dropwise at 0 °C under nitrogen atmosphere. The resulting mixture was stirred for 5 hr at room temperature under nitrogen atmosphere, then basified to pH 7 with NH ₃ in methanol (7 M) at 0 °C, diluted with water (20 mL) and extracted with CH ₂ Cl ₂ (3 x 20 mL). The organic layers were combined, washed with brine (1 x 20 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was dissolved in methanol (3 mL). A precipitate formed that was collected by filtration and washed with methanol (3 x 1 mL) to afford 2,4-dimethyl-6-(6-{3-[(1-methylcyclopropyl)amino]pyrrolidin- 1-yl}-1,5- naphthyridin-2-yl)-1,3-benzoxazol-5-ol (200 mg) as a solid. The solid was purified by prep- HPLC (Condition 1, Gradient 27) to afford 2,4-dimethyl-6-(6-{3-[(1-methylcyclopropyl)amino] pyrrolidin-1-yl}-1,5-naphthyridin-2-yl)-1,3-benzoxazol-5-ol (100 mg) as a solid. LCMS (ESI, m/z): 430[M+H]. ¹ H NMR (400 MHz, DMSO-d6)μ δ 14.λλ (s, 1H), 8.40 (d, J = 9.3 Hz, 1H), 8.24 (s, 1H), 8.09 (dd, J = 22.2, 9.2 Hz, 2H), 7.14 (d, J = λ.3 Hz, 1H), δ 3.77 (s, 1H), 3.64 (t, J = 5.7 Hz, 2H), 3.52 (d, J = 9.7 Hz, 1H), 3.31(s, 1H), 2.61 (s, 3H), 2.40 (s, 3H), 2.34 (s, 1H), 2.13 (dd, J = 12.1, 6.3 Hz, 1H), 1.88 (d, J = 10.6 Hz, 1H), 1.26 (s, 3H), 0.47 (qd, J = 11.7, 10.6, 2.4 Hz, 2H), 0.38 – 0.28 (m, 2H). 2,4-dimethyl-6-(6-{3-[(1-methylcyclopropyl)amino]pyrrolidin- 1-yl}-1,5-naphthyridin-2-yl)-1,3- benzoxazol-5-ol (185 mg, 0.414 mmol) was purified by chiral prep-HPLC (Condition 4, Gradient 1) to afford 2,4-dimethyl-6-{6-[(3R)-3-[(1-methylcyclopropyl)amino] pyrrolidin-1-yl]- 1,5-naphthyridin-2-yl}-1,3-benzoxazol-5-ol (67.8 mg, 38%, first peak) and 2,4-dimethyl-6-{6- [(3S)-3-[(1-methylcyclopropyl)amino]pyrrolidin-1-yl]-1,5-nap hthyridin-2-yl}-1,3-benzoxazol-5- ol (68.6 mg, 38.05%, second peak) as solids. Compound 310: LCMS (ESI, m/z): 430 [M+H]. 1H NMR (400 MHz, DMSO-d6)μ δ 14.λλ (s, 1H), 8.3λ (d, J = 9.3 Hz, 1H), 8.23 (s, 1H), 8.09 (dd, J = 21.9, 9.2 Hz, 2H), 7.13 (d, J = 9.3 Hz, 1H), 3.76 (s, 1H), 3.67 – 3.60 (m, 2H), 3.53 (s, 1H), 3.30 (s, 1H), 2.61 (s, 3H), 2.40 (s, 3H), 2.13 (dq, J = 12.9, 6.3 Hz, 1H), 1.95 – 1.77 (m, 1H), 1.26 (s, 3H), 0.48 (tt, J = 11.0, 6.0 Hz, 2H), 0.33 (d, J = 3.2 Hz, 2H). Compound 311: LCMS (ESI, m/z): 430 [M+H]. ¹ H NMR (400 MHz, DMSO-d6)μ δ 14.λλ (s, 1H), 8.40 (d, J = 9.2 Hz, 1H), 8.24 (s, 1H), 8.12 (d, J = 9.2 Hz, 1H), 8.07 (d, J = 9.1 Hz, 1H), 7.14 (d, J = 9.3 Hz, 1H), 3.77 (s, 1H), 3.68 – 3.60 (m, 2H), 3.52 (d, J = 9.5 Hz, 1H), 3.30 (s, 1H), 2.61 (s, 3H), 2.40 (s, 3H), 2.19 – 2.08 (m, 1H), 1.88 (s, 1H), 1.26 (s, 3H), 0.54 – 0.41 (m, 2H), 0.33 (d, J = 3.3 Hz, 2H). Example 118: Synthesis of Compounds 295 and 296 Synthesis of Intermediate C36 A mixture of tert-butyl N-[1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3-yl]-N- (cyclopropylmethyl)carbamate (500 mg, 1.241 mmol, 1 equiv), 5-methoxy-2,4-dimethyl-6- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol e (376 mg, 1.241 mmol, 1 equiv), Pd(DtBPF)Cl ₂ (81 mg, 0.124 mmol, 0.1 equiv), and K3PO4 (790 mg, 3.723 mmol, 3 equiv) in dioxane (10 mL) and water (2 mL) was stirred for 16 hr at 80 °C under nitrogen atmosphere. The reaction mixture was cooled to room temperature, then poured into water (20 mL) and extracted with ethyl acetate (3 x 20 mL), dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford tert-butyl N- (cyclopropylmethyl)-N-{1-[6-(5-methoxy-2,4-dimethyl-1,3-benz oxazol-6-yl)-1,5-naphthyridin- 2-yl]pyrrolidin-3-yl}carbamate (360 mg, 53%) as a solid. LCMS (ES, m/z):544 [M+H] ⁺ . To a stirred solution of tert-butyl N-(cyclopropylmethyl)-N-{1-[6-(5-methoxy-2,4-dimethyl-1,3- benzoxazol-6-yl)-1,5-naphthyridin-2-yl]pyrrolidin-3-yl}carba mate (360 mg, 0.662 mmol, 1 equiv) in DCM (7.2 mL) was added BBr3 (829 mg, 3.310 mmol, 5.00 equiv) dropwise at 0 °C. The resulting mixture was stirred for 16 hr at room temperature, then quenched with methanol (30 mL) at 0 °C, basified to pH 8 with saturated NaHCO ₃ (aq.), and extracted with CH ₂ Cl ₂ (3 x 50 mL), dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by chiral prep-HPLC (Condition 3, Gradient 22) to afford 6-(6-{3-[(cyclopropylmethyl)amino]pyrrolidin-1-yl}-1,5- naphthyridin-2-yl)-2,4-dimethyl-1,3-benzoxazol-5-ol (140 mg) as a solid. LCMS (ES, m/z):430 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 14.λλ (s, 1H), 8.41 (d, J = 9.3 Hz, 1H), 8.25 (s, 1H), 8.14 (dd, J = 9.2, 0.8 Hz, 1H), 8.07 (dd, J = 9.1, 0.8 Hz, 1H), 7.16 (d, J = 9.3 Hz, 1H), 3.74 (dd, J = 10.5, 5.8 Hz, 1H), 3.68 (s, 1H), 3.60 – 3.51 (m, 1H), 3.45 (t, J = 5.4 Hz, 1H), 3.41 – 3.30 (s, 1H), 2.61 (s, 3H), 2.46 (d, J = 6.8 Hz, 2H), 2.40 (s, 3H), 2.13 (dq, J = 12.9, 6.5 Hz, 1H), 1.87 (dd, J = 12.4, 6.4 Hz, 1H), 0.95 – 0.84 (m, 1H), 0.46 – 0.33 (m, 2H), 0.17 – 0.09 (m, 2H). Synthesis of Compounds 295 and 296 6-(6-{3-[(cyclopropylmethyl)amino]pyrrolidin-1-yl}-1,5-napht hyridin-2-yl)-2,4-dimethyl-1,3- benzoxazol-5-ol (120 mg, 0.279 mmol, 1 equiv) was purified by chiral prep-HPLC (Column: CHIRAL ART Cellulose-SB, 2 x 25 cm, 5 um; Mobile Phase A: MtBE(0.1% DEA)-HPLC, Mobile Phase B: MeOH--HPLC; Flow rate: 20 mL/min; Gradient: 20% B to 20% B in 7 min; Wave Length: UV 220/254 nm; RT1(min): 5.6; RT2(min)) to afford Compound 295 (40.2 mg) and Compound 296 (36.7 mg) as solids. Compound 295: LCMS (ES, m/z):430 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 14.λλ (s, 1H), 8.41 (d, J = 9.2 Hz, 1H), 8.25 (s, 1H), 8.15 (d, J = 9.2 Hz, 1H), 8.08 (d, J = 9.2 Hz, 1H), 7.17 (d, J = 9.3 Hz, 1H), 3.74 (dd, J = 10.8, 5.8 Hz, 1H), 3.68 (s, 1H), 3.58 (s, 1H), 3.46 (t, J = 5.6 Hz, 1H), 3.46 – 3.32 (m, 1H), 2.61 (s, 3H), 2.47 (d, J = 6.7 Hz, 2H), 2.40 (s, 3H), 2.14 (dq, J = 12.7, 6.5 Hz, 1H), 1.92 – 1.84 (m, 1H), 0.94 – 0.84 (m, 1H), 0.46 – 0.35 (m, 2H), 0.17 – 0.09 (m, 2H). Compound 296: LCMS (ES, m/z):430 [M+H] ⁺ . 1H NMR (400 MHz, DMSO-d6) δ 15.00 (s, 1H), 8.42 (d, J = 9.3 Hz, 1H), 8.26 (s, 1H), 8.15 (d, J = 9.3 Hz, 1H), 8.08 (d, J = 9.0 Hz, 1H), 7.17 (d, J = 9.3 Hz, 1H), 3.75 (dd, J = 10.8, 5.8 Hz, 1H), 3.68 (s, 1H), 3.58 (s, 1H), 3.46 (t, J = 5.7 Hz, 1H), 3.46 – 3.30 (m, 1H), 2.47 (d, J = 6.1 Hz, 5H), 2.40 (s, 3H), 2.13 (dt, J = 13.0, 6.4 Hz, 1H), 1.92 – 1.84 (m, 1H), 0.96 – 0.84 (m, 1H), 0.46 – 0.37 (m, 2H), 0.18 – 0.10 (m, 2H). Example 119: Synthesis of Compound 297 Synthesis of Intermediate C38 To a stirred mixture of 2,6-dichloro-1,5-naphthyridine (300 mg, 1.507 mmol, 1 equiv) and 6- (methoxymethoxy)-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)indazole (479.60 mg, 1.507 mmol, 1 equiv) in dioxane (6 mL) and water (1.2 mL) was added Pd(dppf)Cl ₂ CH ₂ Cl ₂ (122.79 mg, 0.151 mmol, 0.1 equiv) and K ₃ PO ₄ (959.85 mg, 4.521 mmol, 3 equiv) at room temperature under nitrogen atmosphere. The mixture was stirred at 80 °C for 1 hr. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 2-chloro-6- [6-(methoxymethoxy)- 2-methylindazol-5-yl]-1,5-naphthyridine (260 mg, 49%) as a solid. Synthesis of Intermediate C39 To a stirred mixture of 2-chloro-6-[6-(methoxymethoxy)-2-methylindazol-5-yl]-1,5- naphthyridine (100 mg, 0.282 mmol, 1 equiv) and tert-butyl N-{bicyclo[1.1.1]pentan-1-yl}-N- (pyrrolidin-3-yl)carbamate (85.35 mg, 0.338 mmol, 1.2 equiv) in DMSO (3 mL) was added DIEA (109.28 mg, 0.846 mmol, 3 equiv) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred at 100 °C overnight, then extracted with ethyl acetate (2 x 20 mL). The organic layers were combined, washed with water (2 x 20 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to give tert-butyl N-{bicyclo[1.1.1]pentan-1-yl}-N-(1-{6-[6-(methoxymethoxy)-2- methylindazol -5-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl)carbamate (150 mg) as a solid. Synthesis of Compound 297 To a stirred mixture of tert-butyl N-{bicyclo[1.1.1]pentan-1-yl}-N-(1-{6-[6-(methoxymethoxy)- 2-methylindazol-5-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl) carbamate (150 mg, 0.263 mmol, 1 equiv) in methanol (1.5 mL, 37.048 mmol, 140.96 equiv) was added HCl (gas) in 1,4-dioxane (1.5 mL, 49.368 mmol, 187.83 equiv) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 2 hr, then concentrated under reduced pressure to give a residue. The residue product was purified by reverse phase (Condition 5, Gradient 1) to afford 5-[6-(3-{bicyclo[1.1.1]pentan-1-ylamino}pyrrolidin-1-yl)-1,5 - naphthyridin-2-yl]-2-methylindazol-6-ol (47.9 mg, 43%) as a solid. LCMS (ES, m/z): 427 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.λ7 (s, 1H), 8.54 (s, 1H), 8.39 (d, J = 9.2 Hz, 1H), 8.35 (s, 1H), 8.08 (dd, J = 12.9, 9.2 Hz, 2H), 7.14 (d, J = 9.3 Hz, 1H), 6.87 (s, 1H), 4.11 (s, 3H), 3.78 (dd, J = 10.6, 6.2 Hz, 1H), 3.68 (s, 1H), 3.55 (t, J = 8.3 Hz, 1H), 3.47 (s, 1H), 3.32 (s, 1H), 2.77 (s, 1H), 2.37 (s, 1H), 2.16 (dq, J = 12.6, 6.2 Hz, 1H), 1.78 (d, J = 1.7 Hz, 7H). Example 120: Synthesis of Compound 333 Synthesis of Intermediate C40 A mixture of 6-bromo-2-cyclopropyl-5-methoxy-1,3-benzoxazole (200 mg, 0.746 mmol, 1 equiv), 4,4,5,5-tetramethyl-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)- 1,3,2-dioxaborolane (568 mg, 2.238 mmol, 3 equiv), Pd(dppf)Cl ₂ (55 mg, 0.075 mmol, 0.1 equiv), and KOAc (220 mg, 2.238 mmol, 3 equiv) in 1,4-dioxane (8 mL) was stirred for 24 hr at 80 °C under nitrogen atmosphere. The resulting mixture was cooled to room temperature, then poured into the water (50 mL) and extracted with ethyl acetate (1 x 40 mL), dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to afford 2-cyclopropyl-5- methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3- benzoxazole (589 mg) as a solid. LCMS (ES, m/z): 316 [M+H] ⁺ . Synthesis of Intermediate C41 A mixture of N-tert-butyl-1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3- amine (175 mg, 0.574 mmol, 1 equiv), 2-cyclopropyl-5-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxabo rolan-2-yl)-1,3- benzoxazole (452.37 mg, 1.435 mmol, 2.5 equiv), Pd(DtBPF)Cl ₂ (37 mg, 0.057 mmol, 0.1 equiv), and K ₃ PO ₄ (366 mg, 1.722 mmol, 3 equiv) in 1,4-dioxane (8.4 mL) and water (2.1 mL) was stirred for 2 hr at 80°C under nitrogen atmosphere. The resulting mixture was cooled to room temperature and extracted with ethyl acetate (1 x 50 mL). The organic layers were combined, dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ / MeOH (10:1) to afford N-tert-butyl-1-[6-(2- cyclopropyl-5-methoxy-1,3-benzoxazol-6-yl)-1,5-naphthyridin- 2-yl]pyrrolidin-3-amine (65 mg, 25%) as a solid. LCMS (ES, m/z):458 [M+H] ⁺ . Synthesis of Compound 333 To a stirred solution of N-tert-butyl-1-[6-(2-cyclopropyl-5-methoxy-1,3-benzoxazol-6- yl) -1,5- naphthyridin-2-yl]pyrrolidin-3-amine (65 mg, 0.142 mmol, 1 equiv) in DCM (6.5 mL) was added BBr ₃ (355.87 mg, 1.420 mmol, 10 equiv) dropwise at 0 °C under nitrogen atmosphere. The resulting mixture was quenched with methanol (25 mL) at 0 °C, then neutralized to pH 9 with saturated NaHCO ₃ (aq.). The resulting mixture was extracted with CH ₂ Cl ₂ (1 x 10mL). The orgni layers were combined, dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Column: XBridge Prep OBD C ₁₈ Column, 30x150 mm, 5μm; Mobile Phase Aμ Water (10 mmol/L NH ₄ HCO ₃ ), Mobile Phase B: ACN; Flow rate: 60 mL/min; Gradient: 40% B to 70% B in 8 min, 70% B; Wave Length: UV 220 nm; RT1(min): 7.62)) to afford 6-{6-[3-(tert- butylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2-yl}-2-cyclopr opyl -1,3-benzoxazol-5-ol (8.9 mg, 14%) as a solid. LCMS (ES, m/z):444 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.54 (s, 1H), 8.43 – 8.35 (m, 2H), 8.14 – 8.04 (m, 2H), 7.15 (d, J = 9.3 Hz, 1H), 7.06 (s, 1H), 3.86 (s, 1H), 3.72 (s, 1H), 3.50 (s, 2H), 3.14 (s, 1H), 2.32 – 2.22 (m, 1H), 2.19 (s, 1H), 1.77 (s, 2H), 1.21 (m, 2H), 1.16 (m, 2H), 1.10 (s, 9H). Example 121: Synthesis of Compound 453 Synthesis of Compound C42 To a stirred mixture of 6-chloro-1,7-naphthyridin-2-ol (200 mg, 1.107 mmol, 1 equiv) and tert- butyl piperazine-1-carboxylate (309.41 mg, 1.660 mmol, 1.5 equiv) in acetonitrile (4 mL) was added DBU (505.81 mg, 3.321 mmol, 3 equiv) and BOP (979.65 mg, 2.214 mmol, 2 equiv) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at room temperature. A precipitate formed that was collected by filtration, then washed with acetonitrile (2x2 mL) to afford tert-butyl 4-(6-chloro-1,7-naphthyridin-2-yl)piperazine-1- carboxylate (70 mg, 18%) as a solid. Synthesis of Intermediate C43 To a stirred mixture of tert-butyl 4-(6-chloro-1,7-naphthyridin-2-yl)piperazine-1-carboxylate (60 mg, 0.172 mmol, 1 equiv) and Pd(dtbpf)Cl ₂ (11.21 mg, 0.017 mmol, 0.1 equiv) in dioxane (2 mL) was added Sn ₂ Me ₆ (112.71 mg, 0.344 mmol, 2 equiv) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 100 °C, then quenched with KF at room temperature. The resulting mixture was filtered and the filter cake was washed with ethyl acetate (2x5 mL). The filtrate was concentrated under reduced pressure to give a residue. The residue was partitioned between water and ethyl acetate, then extracted with ethyl acetate (2 x 5 mL). The organic layers were combined, washed with brine (2x10 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. Synthesis of Intermediate C44 To a stirred mixture of 6-bromo-2,8-dimethylimidazo[1,2-a]pyrazine (78.17 mg, 0.347 mmol, 1.5 equiv) and Pd(dtbpf)Cl ₂ (15.02 mg, 0.023 mmol, 0.1 equiv) in dioxane (3 mL) was added tert-butyl 4-[6-(trimethylstannyl)-1,7-naphthyridin-2-yl]piperazine-1-c arboxylate (110 mg, 0.231 mmol, 1 equiv) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 100 °C, then quenched with water at room temperature and extracted with ethyl acetate (2 x 10 mL). The organic layers were combined, washed with brine (2x10 mL), dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by Prep-TLC (CH ₂ Cl ₂ / MeOH 10:1) to afford tert-butyl 4-(6-{2,8-dimethylimidazo [1,2-a]pyrazin-6-yl}-1,7- naphthyridin-2-yl)piperazine-1-carboxylate (100 mg, 28%) as a solid. Synthesis of Compound 453 To a stirred solution of tert-butyl 4-(6-{2,8-dimethylimidazo[1,2-a]pyrazin-6-yl}-1,7- naphthyridin -2-yl)piperazine-1-carboxylate (30 mg, 0.065 mmol, 1 equiv) in methanol (1 mL) was added HCl (gas) in 1,4-dioxane (1 mL) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 1 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by reverse phase chromatography (Gradient: isocratic) to afford 6-{2,8-dimethylimidazo[1,2-a]pyrazin-6-yl}-2- (piperazin-1-yl)-1,7-naphthyridine (1.2 mg, 5%) as a solid. LCMS (ES, m/z): 360 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ λ.47 (s, 1H), λ.21 (s, 2H), λ.05 (s, 1H), 8.61 (s, 1H), 8.3λ (d, J = 9.3 Hz, 1H), 8.18 (s, 1H), 7.62 (d, J = 9.3 Hz, 1H), 4.03 (t, J = 5.3 Hz, 4H), 3.25 (s, 4H), 2.89 (s, 3H), 2.48 (s, 3H). Example 122: Synthesis of Compounds 358 and 359 Synthesis of Intermediate C45 To a stirred mixture of 5-bromo-6-(methoxymethoxy)-2,7-dimethylindazole (100 mg, 0.35 mmol, 1 equiv) and tert-butyl N-[(1r,3r)-3-fluorocyclobutyl]-N-[(3S)-1-[6-(trimethylstanny l)- 1,5-naphthyridin-2-yl] pyrrolidin-3-yl] carbamate (288.95 mg, 0.52 mmol, 1.5 equiv) in dioxane (3 mL) was added Pd(DtBPF)Cl ₂ (22.86 mg, 0.03 mmol, 0.1 equiv) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 100 °C, then filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ / MeOH (10:1) to afford tert-butyl N-(1-{6-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]-1,5- naphthyridin-2-yl}pyrrolidin-3-yl)-N-[(1r,3r)-3-fluorocyclob utyl]carbamate (80 mg, 39%) as a solid. Synthesis of Compound 358 and 359

To a stirred solution of tert-butyl N-(1-{6-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl] -1,5- naphthyridin-2-yl}pyrrolidin-3-yl)-N-[(1r,3r)-3-fluorocyclob utyl] carbamate (80 mg, 0.13 mmol, 1 equiv) in methanol (1 mL) was added HCl (gas) in 1,4-dioxane (1 mL) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 1 hr at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (Condition 2, Gradient 14) followed by chiral prep- HPLC (Condition 4, Gradient 4) to afford 2,7-dimethyl-5-{6-[(3S)-3-{[(1r,3r)-3- fluorocyclobutyl]amino}pyrrolidin-1-yl] -1,5-naphthyridin-2-yl}indazol-6-ol (2.8 mg, 5%) and 2,7-dimethyl-5-{6-[(3R)-3-{[(1r,3r)-3-fluorocyclobutyl] amino} pyrrolidin-1-yl]-1,5- naphthyridin-2-yl} indazol-6-ol (2.1 mg, 3%) as solids. Compound 358: LCMS (ES, m/z): 447 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.32 (s, 1H), 8.40-8.33 (t, J = 4.7 Hz, 3H), 8.14- 8.06 (d, J = 9.2 Hz,2H), 7.17 (d, J = 9.3 Hz, 1H), 5.27 (s, 1H), 4.13 (s, 3H), 3.74-3.57 (s, 4H), 3.43 (s, 1H), 2.38 (s, 6H), 2.16 (s, 3H), 1.86 (s, 1H). Compound 359: LCMS (ES, m/z): 447 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.32 (s, 1H), 8.40-8.33 (t, J = 4.7 Hz, 3H), 8.14- 8.06 (d, J = 9.2 Hz,2H), 7.17 (d, J = 9.3 Hz, 1H), 5.27 (s, 1H), 4.13 (s, 3H), 3.74-3.57 (s, 4H), 3.43 (s, 1H), 2.38 (s, 6H), 2.16 (s, 3H), 1.86 (s, 1H). Example 123: Synthesis of Compounds 348 and 350 Synthesis of Intermediate C47 A mixture of 6-bromo-5-methoxy-2-methyl-1,3-benzoxazole (250 mg, 1.033 mmol, 1 equiv), DCM (5 mL), and BBr3 (1293.62 mg, 5.165 mmol, 5 equiv, 1 mol/L in DCM) was stirred for 5 h at room temperature. The reaction mixture was quenched with methanol (20 mL) at 0 °C, then concentrated under reduced pressure to give a residue. The residue was dissolved in CH ₂ Cl ₂ (20 mL), basified to pH 7 with saturated NaHCO ₃ (aq.), and extracted with CH ₂ Cl ₂ (3x10 mL). The organic layers were combined, washed with brine (1 x 20 mL), dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give 6- bromo-2-methyl-1,3-benzoxazol-5-ol (200 mg, 85%). LCMS (ES, m/z):228 [M+H] ⁺ . Synthesis of Intermediate C48 6-bromo-2-methyl-1,3-benzoxazol-5-ol (150 mg, 0.658 mmol, 1 equiv), tert-butyl N-[(1r,3r)-3- fluorocyclobutyl]-N-{1-[6-(trimethylstannyl)-1,5-naphthyridi n-2-yl] pyrrolidin-3-yl} carbamate (361.30 mg, 0.658 mmol, 1 equiv), dioxane (15 mL, 177.059 mmol, 269.18 equiv), and Pd(dppf)Cl ₂ CH ₂ Cl ₂ (53.58 mg, 0.066 mmol, 0.1 equiv) were combined at room temperature. The resulting mixture was stirred for 4 hr at 100 °C under nitrogen atmosphere, then cooled to room temperature and quenched with water (30 mL) at room temperature and extracted with ethyl acetate (3 x 20 mL). The organic layers were combined, washed with brine (1x30 mL), dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by Prep-TLC (CH ₂ Cl ₂ /MeOH=10:1) to afford tert-butyl N-{1-[6-(5-hydroxy-2-methyl-1,3-benzoxazol -6-yl)-1,5-naphthyridin-2- yl]pyrrolidin-3-yl}-N-[(1r,3r)-3-fluorocyclobutyl]carbamate (70 mg, 16%) as a solid. LCMS (ES, m/z):534 [M+H] ⁺ . Synthesis of Compounds 348 and 350

A mixture of tert-butyl N-{1-[6-(5-hydroxy-2-methyl-1,3-benzoxazol-6-yl) -1,5-naphthyridin-2- yl]pyrrolidin-3-yl}-N-[(1r,3r)-3-fluorocyclobutyl] carbamate (65 mg, 0.122 mmol, 1 equiv) and HCl (gas) in 1,4-dioxane (3 mL) was stirred for 1 h at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep- HPLC(Condition 1, Gradient 28) , followed by chiral-HPLC (Condition 4, Gradient 9) to afford 2-methyl-6-{6-[(3R)-3-{[(1r,3r) -3-fluorocyclobutyl]amino}pyrrolidin-1-yl]-1,5-naphthyridin- 2- yl}-1,3-benzoxazol-5-ol (5.5 mg, 10%) and 2-methyl-6-{6-[(3S)-3-{[(1r,3r)-3-fluorocyclobutyl] amino} pyrrolidin-1-yl]-1,5-naphthyridin-2-yl}-1,3-benzoxazol-5-ol (6.5 mg, 12%) as solids. Compound 348: LCMS (ES, m/z):434 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 14.51 (s, 1H), 8.46 – 8.39 (m, 2H), 8.16 – 8.05 (m, 2H), 7.17 (d, J = 9.3 Hz, 1H), 7.12 (s, 1H), 5.19 (ddq, J = 57.0, 6.4, 3.3 Hz, 1H), 3.79 – 3.63 (m, 2H), 3.57 (s, 2H), 3.40 (s, 2H), 2.61 (s, 3H), 2.40 – 2.28 (m, 2H), 2.25 – 2.05 (m, 3H), 1.85 (s, 1H). Compound 350: LCMS (ES, m/z):434 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.52 (s, 1H), 8.46 – 8.39 (m, 2H), 8.10 (ddd, J = 17.2, 9.2, 0.8 Hz, 2H), 7.17 (d, J = 9.3 Hz, 1H), 7.12 (s, 1H), 5.19 (dtt, J = 56.9, 6.4, 3.6 Hz, 1H), 3.76 – 3.69 (m, 2H), 3.56 (s, 2H), 3.38 (s, 2H), 2.61 (s, 3H), 2.43 – 2.27 (m, 2H), 2.23 – 2.04 (m, 3H), 1.84 (s, 1H). Example 124: Synthesis of Compounds 353 and 357 Synthesis of Intermediate C49

A solution of 1-(6-chloro-1,5-naphthyridin-2-yl)-N-[1-(fluoromethyl)cyclop ropyl]pyrrolidin-3- amine (190 mg, 0.592 mmol, 1 equiv) in dioxane (4 mL) and water (0.8 mL) was treated with K ₃ PO ₄ (377.15 mg, 1.776 mmol, 3 equiv) and Pd(dppf)Cl ₂ (43.34 mg, 0.059 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. To the reaction mixture was added 7-fluoro-6- (methoxymethoxy)-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)indazole (238.92 mg, 0.710 mmol, 1.2 equiv) in portions at room temperature. The resulting mixture was stirred for 2 h at 80 °C, then concentrated under vacuum to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ /MeOH (9:1) to afford 1-{6-[7-fluoro-6- (methoxymethoxy)-2-methylindazol-5-yl]-1,5-naphthyridin-2-yl }-N-[1- (fluoromethyl)cyclopropyl]pyrrolidin-3-amine (180 mg, 61%) as a solid. Synthesis of Compound 353 and 357 A mixture of 1-{6-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5-yl]-1,5- naphthyridin -2- yl}-N-[1-(fluoromethyl)cyclopropyl]pyrrolidin-3-amine (180 mg, 0.364 mmol, 1 equiv) and HCl (gas) in 1,4-dioxane (2 mL, 65.826 mmol, 180.85 equiv) in methanol (2 mL, 0.062 mmol, 0.17 equiv) was stirred for 2 hr at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under vacuum to give a residue. The residue product was purified by reverse phase flash chromatography (Condition 5, Gradient 2), followed by chiral-HPLC (Condition 4, Gradient 1) to afford 7-fluoro-5-{6-[(3R)-3-{[1-(fluoromethyl)cyclopropyl]amino}py rrolidin-1- yl]-1,5-naphthyridin-2-yl}-2-methylindazol-6-ol (8.6 mg, 5%) and 7-fluoro-5-{6-[(3S)-3-{[1- (fluoromethyl) cyclopropyl]amino}pyrrolidin-1-yl]-1,5-naphthyridin-2-yl}-2- methylindazol-6-ol (12.8 mg, 8%) as solids. Compound 353: LCMS (ES, m/z): 451 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 14.43 (s, 1H), 8.48 (d, J = 2.8 Hz, 1H), 8.41 (t, J = 4.7 Hz, 2H), 8.11 (dd, J = 20.3, 9.1 Hz, 2H), 7.16 (d, J = 9.3 Hz, 1H), 4.47 (s, 1H), 4.35 (s, 1H), 4.16 (s, 3H), 3.82 – 3.75 (m, 1H), 3.70 (s, 2H), 3.55 (s, 1H), 2.67 (s, 1H), 2.15 (s, 1H), 1.90 (s, 1H), 0.62 (s, 4H). Compound 357: LCMS (ES, m/z): 451 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 14.42 (s, 1H), 8.48 (d, J = 2.7 Hz, 1H), 8.41 (t, J = 4.7 Hz, 2H), 8.14 (d, J = 9.2 Hz, 1H), 8.09 (d, J = 9.0 Hz, 1H), 7.16 (d, J = 9.2 Hz, 1H), 4.47 (s, 1H), 4.35 (s, 1H), 4.16 (s, 3H), 3.79 (s, 1H), 3.70 (s, 2H), 3.54 (s, 1H), 3.08 (s, 1H), 2.79 – 2.58 (m, 1H), 2.14 (s, 1H), 1.91 (s, 1H), 0.62 (s, 4H). Example 125: Synthesis of Compounds 354 and 355 Synthesis of Intermediate C51 A mixture of 1-(6-chloro-1,5-naphthyridin-2-yl)-N-[1-(fluoromethyl)cyclop ropyl]pyrrolidin-3- amine (170 mg, 0.530 mmol, 1 equiv) and Pd(dtbpf)Cl ₂ (34.54 mg, 0.053 mmol, 0.1 equiv) in dioxane (2 mL) and water (2 mL) was treated with K ₃ PO ₄ (337.45 mg, 1.590 mmol, 3 equiv) at room temperature under nitrogen atmosphere. To the reaction mixture was added 6- (methoxymethoxy)-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)indazole (202.33 mg, 0.636 mmol, 1.2 equiv) in portions at room temperature. The resulting mixture was stirred for 2 h at 80 °C, then concentrated under vacuum to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ / MeOH (9:1) to afford N-[1- (fluoromethyl)cyclopropyl]-1-{6-[6-(methoxymethoxy)-2-methyl indazol-5-yl]-1,5-naphthyridin- 2-yl}pyrrolidin-3-amine (160 mg, 63%) as a solid. Synthesis of Compounds 354 and 355

A mixture of N-[1-(fluoromethyl)cyclopropyl]-1-{6-[6-(methoxymethoxy)-2-m ethylindazol -5- yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-amine (160 mg, 0.336 mmol, 1 equiv) and HCl (gas) in 1,4-dioxane (2 mL) in methanol (2 mL, 0.062 mmol, 0.19 equiv) was stirred for 2 h at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by reverse phase flash chromatography (Condition 5, Gradient 3) followed by chiral-HPLC (Condition 4, Gradient 1) to afford 5-{6-[(3R)-3-{[1- (fluoromethyl)cyclopropyl]amino}pyrrolidin -1-yl]-1,5-naphthyridin-2-yl}-2-methylindazol-6-ol (10.4 mg, 7%) and 5-{6-[(3S)-3-{[1-(fluoromethyl)cyclopropyl]amino}pyrrolidin- 1-yl]-1,5- naphthyridin-2-yl}-2-methylindazol-6-ol (8.6 mg, 6%) as solids. Compound 354: LCMS (ES, m/z): 433 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.λ7 (s, 1H), 8.54 (s, 1H), 8.3λ (d, J = 9.2 Hz, 1H), 8.35 (s, 1H), 8.08 (dd, J = 13.7, 9.2 Hz, 2H), 7.13 (d, J = 9.3 Hz, 1H), 6.87 (s, 1H), 4.47 (s, 1H), 4.35 (s, 1H), 4.11 (s, 3H), 3.77 (d, J = 9.9 Hz, 1H), 3.70 (s, 2H), 3.54 (d, J = 9.1 Hz, 1H), 3.32 (s, 1H), 2.71 (s, 1H), 2.19 – 2.11 (m, 1H), 1.91 (s, 1H), 0.62 (s, 4H). Compound 355: LCMS (ES, m/z): 433 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 13.λ5 (s, 1H), 8.54 (s, 1H), 8.40 (d, J = 9.2 Hz, 1H), 8.35 (s, 1H), 8.19 – 8.03 (m, 2H), 7.16 (s, 1H), 6.87 (s, 1H), 4.42 (d, J = 49.9 Hz, 2H), 4.11 (s, 3H), 3.71 (s, 3H), 3.56 (s, 1H), 2.92 (dd, J = 12.8, 6.8 Hz, 1H), 2.16 (s, 1H), 1.91 (s, 1H), 0.63 (s, 4H). Example 126: Synthesis of Compound 382 Synthesis of Intermediate C53 A mixture of methyl 2-amino-5-bromopyridine-3-carboxylate (25.0 g, 108.20 mmol, 1 equiv) and PPTS (2.72 g, 10.82 mmol, 0.1 equiv) in 2-Propanol (250 mL) was stirred overnight at 100 °C, then concentrated under vacuum to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ /MeOH (5:1) to afford methyl 6-bromo-2- methylimidazo[1,2-a]pyridine-8-carboxylate (23.4 g, 80%) as a solid. LCMS (ES, m/z): 269 [M+H] ⁺ . Synthesis of Intermediate C55 A solution of methyl 6-bromo-2-methylimidazo[1,2-a]pyridine-8-carboxylate (23.4 g, 86.95 mmol, 1 equiv) in NH ₃ .H ₂ O (234 mL) was stirred overnight at 100 °C in a pressure tank. A precipitate formed that was collected by filtration and washed with water (3x200 mL) to afford 6-bromo-2-methylimidazo[1,2-a]pyridine-8-carboxamide (11.4 g, 52%) as a solid. LCMS (ES, m/z): 254 [M+H] ⁺ . Synthesis of Intermediate C55 A mixture of 6-bromo-2-methylimidazo[1,2-a]pyridine-8-carboxamide (11.4 g, 44.86 mmol, 1 equiv) and POCl ₃ (68.8 g, 448.67 mmol, 10 equiv) in toluene (114 mL) was stirred overnight at 120 °C, then concentrated under vacuum. The resulting mixture was diluted with water (50 mL) and basified to pH 8 with saturated NaHCO ₃ (aq.). A precipitate formed that was collected by filtration and washed with water (3 x 50 mL) to afford 6-bromo-2-methylimidazo[1,2-a]pyridine- 8-carbonitrile (8.63 g, 82%) as a solid. LCMS (ES, m/z): 236 [M+H] ⁺ . Synthesis of Intermediate C56 A mixture of 6-bromo-2-methylimidazo[1,2-a]pyridine-8-carbonitrile (3.13 g, 13.25 mmol, 1 equiv), bis(pinacolato)diboron (4.38 g, 17.23 mmol, 1.3 equiv), potassium acetate (3.90 g, 39.77 mmol, 3 equiv), and Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (0.54 g, 0.66 mmol, 0.05 equiv) in dioxane (40 mL) was stirred for 4 hr at 80 °C under nitrogen atmosphere. LCMS (ES, m/z): 202 [M+H] ⁺ . Synthesis of Intermediate C53 A mixture of 2-bromopyrido[3,2-d]pyrimidin-6-ol (3.0 g, 13.27 mmol, 1 equiv), 8-cyano-2- methylimidazo[1,2-a]pyridin-6-ylboronic acid (2.93 g, 14.59 mmol, 1.1 equiv), Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (0.54 g, 0.664 mmol, 0.05 equiv), and K ₃ PO ₄ (8.45 g, 39.81 mmol, 3 equiv) in dioxane (48 mL) and water (12 mL) was stirred overnight at 80 °C under nitrogen atmosphere. The resulting mixture was diluted with water (100 mL). A precipitate formed that was collected by filtration and washed with water (3 x 50 mL) to afford 6-{6-hydroxypyrido[3,2-d]pyrimidin- 2-yl}-2-methylimidazo[1,2-a]pyridine-8-carbonitrile (2.15 g, 54%) as a solid. LCMS (ES, m/z): 303 [M+H] ⁺ . Synthesis of Intermediate C59

A mixture of 6-{6-hydroxypyrido[3,2-d]pyrimidin-2-yl}-2-methylimidazo[1,2 -a]pyridine-8- carbonitrile (900 mg, 2.97 mmol, 1 equiv) and POCl ₃ (4564.6 mg, 29.77 mmol, 10 equiv) in acetonitrile (10 mL) was stirred overnight at 80 °C. The resulting mixture was concentrated under vacuum to give a residue. The residue was basified to pH 8 with saturated NaHCO ₃ (aq.). A precipitate formed that was collected by filtration and washed with water (3 x 30 mL) to afford 6-{6-chloropyrido[3,2-d]pyrimidin-2-yl}-2-methylimidazo[1,2- a]pyridine-8-carbonitrile (720 mg, 75%) as a solid. LCMS (ES, m/z): 321 [M+H] ⁺ . Synthesis of Intermediate C60 A mixture of 6-{6-chloropyrido[3,2-d]pyrimidin-2-yl}-2-methylimidazo[1,2- a]pyridine-8- carbonitrile (220 mg, 0.68 mmol, 1 equiv), tert-butyl N-methyl-N-(pyrrolidin-3-yl)carbamate (206.0 mg, 1.02 mmol, 1.5 equiv), and DIEA (265.9 mg, 2.05 mmol, 3 equiv) in DMSO (4 mL) was stirred overnight at 100 °C. The resulting mixture was diluted with water (30 mL) and extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, washed with brine (1x30 mL), dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:1) to afford tert-butyl N-[1-(2-{8-cyano-2- methylimidazo[1,2-a]pyridin-6-yl}pyrido[3,2-d]pyrimidin-6-yl )pyrrolidin-3-yl]-N- methylcarbamate (85.0 mg, 26%) as a solid. LCMS (ES, m/z): 485 [M+H] ⁺ . Synthesis of Compound 382

A mixture of tert-butyl N-[1-(2-{8-cyano-2-methylimidazo[1,2-a]pyridin-6-yl}pyrido[3 ,2- d]pyrimidin-6-yl)pyrrolidin-3-yl]-N-methylcarbamate (85.0 mg, 0.17 mmol, 1 equiv) in DCM (2 mL) and TFA (0.5 mL) was stirred for 2 hr at room temperature. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by prep-HPLC (Condition 1, Gradient 18) to afford 2-methyl-6-{6-[3-(methylamino)pyrrolidin-1-yl]pyrido[3,2- d]pyrimidin-2-yl}imidazo[1,2-a]pyridine-8-carbonitrile (29.0 mg, 43%) as a solid. LCMS (ES, m/z): 385 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ λ.65 (d, J = 1.6 Hz, 1H), 9.10 (s, 1H), 8.54 (d, J = 1.6 Hz, 1H), 8.06 – 7.96 (m, 2H), 7.31 (d, J = 9.4 Hz, 1H), 3.77 – 3.49 (m, 3H), 3.45 – 3.40 (m, 2H), 2.43 – 2.39 (m, 3H), 2.37 (s, 3H), 2.19 – 2.11 (m, 1H), 1.92 (s, 1H). Example 127: Synthesis of Compound 335 Synthesis of Intermediate C61 A mixture of 6-bromo-5-methoxy-2-(oxetan-3-yl)-1,3-benzoxazole (200 mg, 0.704 mmol, 1 equiv), potassium acetate (207 mg, 2.112 mmol, 3 equiv), 4,4,5,5-tetramethyl-2-(tetramethyl- 1,3,2-dioxaborolan-2-yl)-1,3,2- dioxaborolane (536 mg, 2.112 mmol, 3 equiv), and Pd(DtBPF)Cl ₂ (46 mg, 0.070 mmol, 0.1 equiv) in 1,4-dioxane (8 mL) was stirred for 16 hr at 80 °C under nitrogen atmosphere, then cooled to room temperature. The resulting mixture was poured into the water (40 mL) and extracted with ethyl acetate (1 x 40 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to afford 5-methoxy-2-(oxetan-3-yl)-6-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1,3-benzoxazole (588 mg) as a solid. LCMS (ES, m/z): 332 [M+H] ⁺ . Synthesis of Compound 335

A mixture of N-tert-butyl-1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3- amine (215 mg, 0.705 mmol, 1 equiv), 5-methoxy-2-(oxetan-3-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)-1,3- benzoxazole (584 mg, 1.762 mmol, 2.5 equiv), Pd(DtBPF)Cl ₂ (46 mg, 0.070 mmol, 0.1 equiv), and K3PO4 (449 mg, 2.115 mmol, 3 equiv) in 1,4-dioxane (10.3 mL) and water (2.6 mL) was stirred for 2 h at 80 °C under nitrogen atmosphere. The reaction mixture was cooled to room temperature, then extracted with ethyl acetate (1 x 50 mL). The organic layer was dried over anhydrous Na ₂ SO4 and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:1), followed by prep-HPLC (Condition 1, Gradient 21) to afford N-tert-butyl-1- {6-[5-methoxy-2-(oxetan-3-yl) -1,3-benzoxazol-6-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-ami ne (8.9 mg, 3%) as a solid. LCMS (ES, m/z):474 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.10 – 7.91 (m, 3H), 7.91 (dd, J = 8.8, 0.8 Hz, 1H), 7.52 (s, 1H), 7.10 (d, J = 9.4 Hz, 1H), 4.99 (dd, J = 8.6, 5.9 Hz, 2H), 4.90 (dd, J = 6.6, 5.9 Hz, 2H), 4.63 (tt, J = 8.5, 6.6 Hz, 1H), 3.90 (s, 3H), 3.85 (s, 1H), 3.71 (s, 1H), 3.51 (dt, J = 17.3, 8.4 Hz, 2H), 3.17 – 3.08 (m, 1H), 2.18 (d, J = 8.9 Hz, 1H), 1.81 – 1.71 (m, 2H), 1.09 (s, 9H). Example 128: Synthesis of Compound 341 Synthesis of Intermediate C62 A mixture of 2,6-dichloro-1,5-naphthyridine (1 g, 5.024 mmol, 1 equiv) and 6- (methoxymethoxy)-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)indazole (1.92 g, 6.029 mmol, 1.2 equiv) in dioxane (10 mL) and water (2 mL) was treated with K ₃ PO ₄ (3.20 g, 15.072 mmol, 3 equiv) and Pd(dppf)Cl ₂ (0.41 g, 0.502 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The reaction was stirred for 2 hr at 80 °C, then concentrated under vacuum to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 2-chloro-6- [6-(methoxymethoxy) -2-methylindazol-5-yl]-1,5- naphthyridine (550 mg, 31%) as a solid. Synthesis of Intermediate C63 To a solution of 2-chloro-6-[6-(methoxymethoxy)-2-methylindazol-5-yl]-1,5-nap hthyridine (550 mg, 1.550 mmol, 1 equiv) in DMSO (10 mL) was added DIEA (601.08 mg, 4.650 mmol, 3 equiv), followed by tert-butyl N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-N-(pyrrolidin-3- yl)carbamate (502.92 mg, 1.860 mmol, 1.2 equiv) in portions at room temperature. The reaction mixture was stirred for 2 hr at 100 °C. The resulting mixture was extracted with ethyl acetate (2 x 30 mL). The organic layers were combined, washed with brine (2 x 30 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ / PE (1:1) to afford tert-butyl N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-N-(1-{6-[6- (methoxymethoxy)-2-methylindazol-5-yl]-1,5-naphthyridin-2-yl }pyrrolidin-3-yl)carbamate (60 mg, 7%) as a solid. Synthesis of Compound 341 A mixture of tert-butyl N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-N-(1-{6-[6-(methoxymet hoxy) - 2-methylindazol-5-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl) carbamate (60 mg, 0.102 mmol, 1 equiv) and HCl (gas) in 1,4-dioxane (1 mL) in methanol (1 mL) was stirred for 2 h at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by reverse phase flash chromatography (Condition 5, Gradient 4) to afford 5-{6-[3-({3-hydroxybicyclo[1.1.1]pentan-1-yl}amino)pyrrolidi n-1-yl]-1,5- naphthyridin-2-yl}-2-methylindazol-6-ol (9.1 mg, 20%) as a solid. LCMS (ES, m/z): 443 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 13.λ0 (s, 1H), 11.02 (d, J = 8.5 Hz, 1H), 8.55 (s, 1H), 8.42 (d, J = 9.3 Hz, 1H), 8.35 (s, 1H), 8.19 – 8.12 (m, 1H), 8.15 – 8.06 (m, 1H), 7.22 (d, J = 9.3 Hz, 1H), 6.90 – 6.84 (m, 1H), 5.01 (s, 1H), 4.45 (q, J = 5.9 Hz, 1H), 4.11 (s, 3H), 3.94 (dd, J = 10.9, 6.1 Hz, 1H), 3.71 (q, J = 6.9 Hz, 2H), 3.48 (dd, J = 11.0, 4.7 Hz, 1H), 2.40 – 2.32 (m, 1H), 2.05 (s, 3H), 1.99 – 1.90 (m, 1H), 1.85 (s, 3H). Example 129: Synthesis of Compound 360 Synthesis of Intermediate C64 To a mixture of 1-(6-chloro-1,5-naphthyridin-2-yl)-N-[1-(fluoromethyl)cyclop ropyl]pyrrolidin- 3-amine (190 mg, 0.592 mmol, 1 equiv) and K ₃ PO ₄ (377.15 mg, 1.776 mmol, 3 equiv) in dioxane (4 mL) and water (0.8 mL) was added Pd(dppf)Cl ₂ (43.34 mg, 0.059 mmol, 0.1 equiv), followed by 6-(methoxymethoxy)-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2 -dioxaborolan-2- yl)indazole (236.11 mg, 0.710 mmol, 1.2 equiv) at room temperature. The reaction mixture was stirred for 2 h at 80 °C, then cooled to room temperature. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ / MeOH (9:1) to afford N-[1-(fluoromethyl)cyclopropyl]-1-{6-[6- (methoxymethoxy) -2,7-dimethylindazol-5-yl]-1,5-naphthyridin-2-yl}pyrrolidin- 3-amine (50 mg, 17%) as a solid. Synthesis of Compound 360 A mixture of N-[1-(fluoromethyl)cyclopropyl]-1-{6-[6-(methoxymethoxy)-2,7 -dimethylindazol - 5-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-amine (50 mg, 0.102 mmol, 1 equiv) and HCl (gas) in 1,4-dioxane (0.5 mL) in methanol (0.5 mL) was stirred for 2 hr at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by reverse phase flash chromatography (Condition 6, Gradient 1) to afford 5-[6-(3-{[1-(fluoromethyl)cyclopropyl]amino}pyrrolidin-1-yl) -1,5-naphthyridin-2-yl]-2,7- dimethylindazol-6-ol (3.3 mg, 7%) as a solid. LCMS (ES, m/z): 447 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.32 (s, 1H), 8.42 – 8.36 (m, 2H), 8.32 (s, 1H), 8.09 (ddd, J = 23.3, 9.2, 0.8 Hz, 2H), 7.14 (d, J = 9.3 Hz, 1H), 4.47 (s, 1H), 4.35 (s, 1H), 4.13 (s, 3H), 3.77 (d, J = 9.4 Hz, 1H), 3.70 (t, J = 6.0 Hz, 2H), 3.53 (d, J = 8.7 Hz, 1H), 3.34 (d, J = 1.6 Hz, 1H), 2.71 (s, 1H), 2.38 (s, 3H), 2.15 (dd, J = 12.2, 6.3 Hz, 1H), 1.92 – 1.86 (m, 1H), 0.67 – 0.59 (m, 4H). Example 130: Synthesis of Compound 337 Synthesis of Intermediate C65 A mixture of 5-bromo-6-methoxy-2H-indazole (60 g, 264.246 mmol, 1 equiv) and tetrafluoroboranuide; trimethyloxidanium (117 g, 792.738 mmol, 3 equiv) in ethyl acetate (1.2 L) was stirred overnight at room temperature, then quenched with water (2 L) at room temperature. The resulting mixture was basified to pH 8 with saturated NaHCO ₃ (aq.) and extracted with ethyl acetate (3 x 500 mL). The organic layers were combined, washed with brine (1 x 500 mL), dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 5-bromo-6-methoxy-2- methylindazole (45 g, 71%) as a solid. LCMS (ES, m/z): 241 [M+H] ⁺ . Synthesis of Intermediate C66 To a stirred solution of 5-bromo-6-methoxy-2-methylindazole (41 g, 170.062 mmol, 1 equiv) in DCM (800 mL) was added BBr3 (85 g, 340.124 mmol, 2 equiv) dropwise at 0 °C. The resulting mixture was stirred overnight at room temperature, then quenched with water/ice (2 L) at 5 °C and basified to pH 8 with saturated NaHCO ₃ (aq.). A precipitate formed that was collected by filtration and washed with water (3 x 200 mL) to afford 5-bromo-2-methylindazol- 6-ol (38.2 g, 99%) as a solid. LCMS (ES, m/z): 227 [M+H] ⁺ . Synthesis of Intermediate C67 To a stirred solution of 5-bromo-2-methylindazol-6-ol (1.5 g, 6.606 mmol, 1 equiv) in water (8.1 mL) was added NaOH (2.5M) (0.26 g, 166.035 mmol, 1 equiv) dropwise at 5 °C, then stirred for 0.5 h at 5 °C. To the resulting mixture was added HCHO (0.54 g, 17.984 mmol, 2.72 equiv) dropwise at 5 °C and stirred for an additional 1.5 hr at room temperature. A precipitate formed that was collected by filtration and washed with water (2 x 5 mL) to afford 5-bromo-7- (hydroxymethyl)-2-methylindazol-6-ol (1.55 g, 91%) as a solid. LCMS (ES, m/z): 257 [M+H] ⁺ . Synthesis of Intermediate C68 A mixture of 5-bromo-7-(hydroxymethyl)-2-methylindazol-6-ol (37.7 g, 146.643 mmol, 1 equiv) in Et ₃ SiH (400 mL) and TFA (800 mL) was stirred overnight at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was basified to pH 8 with saturated NaHCO ₃ (aq.) and extracted with ethyl acetate (3 x 200 mL). The organic layers were combined, washed with brine (1 x 300 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure. A precipitate formed that was collected by filtration and washed with ethyl ether (3 x 50 mL) to afford 5- bromo-2,7-dimethylindazol-6-ol (28 g, 79%) as a solid. LCMS (ES, m/z): 241 [M+H] ⁺ . Synthesis of Intermediate C69 To a stirred mixture of 5-bromo-2,7-dimethylindazol-6-ol (18 g, 74.662 mmol, 1 equiv) and K ₂ CO ₃ (12.4 g, 89.594 mmol, 1.2 equiv) in DMF (300 mL) was added CH ₃ I (53 g, 373.310 mmol, 5 equiv) dropwise at room temperature. The resulting mixture was stirred for 2 h at room temperature, then quenched with sat. NH ₄ Cl (aq.) (200 mL) at room temperature and extracted with ethyl acetate (3 x 100 mL). The organic layers were combined, washed with brine (1 x 200 mL), dried over anhydrous Na ₂ SO4, and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (4:1) to afford 5-bromo-6-methoxy-2,7-dimethylindazole (16 g, 84%) as a solid. LCMS (ES, m/z): 254 [M+H] ⁺ . Synthesis of Intermediate C70 To a stirred mixture of 5-bromo-6-methoxy-2,7-dimethylindazole (16 g, 62.717 mmol, 1 equiv) and bis(pinacolato)diboron (19.1 g, 75.260 mmol, 1.2 equiv) in dioxane (500 mL) was added KOAc (12.3 g, 125.434 mmol, 2 equiv) and Pd(dppf)Cl ₂ (5.1 g, 6.272 mmol, 0.1 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 80 °C under nitrogen atmosphere, then cooled to room temperature and concentrated under reduced pressure to give a residue. The residue was purified by reverse flash chromatography (Condition 7, Gradient 1) to afford 6-methoxy-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)indazole (9.3 g, 49%) as an oil. LCMS (ES, m/z): 303[M+H] ⁺ . Synthesis of Intermediate C71 To a stirred mixture of 2-bromopyrido[3,2-d]pyrimidin-6-ol (5.5 g, 24.244 mmol, 1 equiv) and 6- methoxy-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborol an-2-yl)indazole (7.3 g, 24.244 mmol, 1 equiv) in dioxane (200 mL) and water (20 mL) was added K3PO4 (15.4 g, 72.732 mmol, 3 equiv) and Pd(dppf)Cl ₂ (1.8 g, 2.424 mmol, 0.1 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 hr at 80 °C under nitrogen atmosphere, then cooled to room temperature and concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ /MeOH (10:1) to afford 2-(6-methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2-d]pyrimidin - 6-ol (4.7 g, 60%) as a solid. LCMS (ES, m/z): 322 [M+H] ⁺ . Synthesis of Intermediate C72 To a stirred solution of 2-(6-methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2-d]pyrimidin -6-ol (4.7 g, 14.626 mmol, 1 equiv) in acetonitrile (100 mL) was added phosphorus oxychloride (22.4 g, 146.260 mmol, 10 equiv) dropwise at 0 °C. The resulting mixture was stirred for 0.5 hr at 80 °C. The resulting mixture was concentrated under reduced pressure, then basified to pH 8 with saturated NaHCO ₃ (aq.) and extracted with ethyl acetate (3 x 100 mL). The organic layers were combined, washed with brine (1 x 100 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:10) to afford 5-{6- chloropyrido[3,2-d]pyrimidin-2-yl}-6-methoxy-2,7-dimethylind azole (1 g, 20%) as a solid. LCMS (ES, m/z): 340 [M+H] ⁺ . Synthesis of Intermediate C73 To a stirred mixture of 5-{6-chloropyrido[3,2-d]pyrimidin-2-yl}-6-methoxy-2,7- dimethylindazole (80 mg, 0.235 mmol, 1 equiv) and tert-butyl N-methyl-N-(pyrrolidin-3- yl)carbamate (94 mg, 0.470 mmol, 2 equiv) in DMSO (5 mL) was added DIEA (152 mg, 1.175 mmol, 5 equiv) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 hr at 120 °C under nitrogen atmosphere, then cooled to room temperature. The resulting mixture was purified by reverse flash chromatography (Condition 7, Gradient 2) to afford tert-butyl N-{1-[2-(6-methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2-d]pyr imidin-6- yl]pyrrolidin-3-yl}-N-methylcarbamate (80 mg, 67%) as a solid. LCMS (ES, m/z): 504 [M+H] ⁺ . Synthesis of Compound 337 To a stirred solution of tert-butyl N-{1-[2-(6-methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2- d]pyrimidin-6-yl]pyrrolidin-3-yl}-N-methylcarbamate (75 mg, 0.149 mmol, 1 equiv) in DCM (5 mL) was added BBr ₃ (187 mg, 0.745 mmol, 5 equiv) dropwise at room temperature. The reaction mixture was stirred for 2 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was quenched with MeOH at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by reverse flash chromatography (Condition 3, Gradient 4) to afford 2,7-dimethyl-5-{6-[3- (methylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyrimidin-2-yl}ind azol-6-ol (20 mg, 34%) as a solid. LCMS (ES, m/z): 390 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 13.32 (s, 1H), λ.26 (s, 1H), 8.84 (s, 1H), 8.39 (s, 1H), 8.17 (d, J = 9.4 Hz, 1H), 7.42 (d, J = 9.4 Hz, 1H), 4.14 (s, 3H), 3.77- 3.60 (m, 3H), 3.40 (s, 3H), 2.40 (s, 3H), 2.33 (s, 3H), 2.17-2.08 (m, 1H), 1.90 (s, 1H). Example 131: Synthesis of Compound 338 Synthesis of Intermediate C74 To a stirred mixture of 5-{6-chloropyrido[3,2-d]pyrimidin-2-yl}-6-methoxy-2,7- dimethylindazole (55 mg, 0.162 mmol, 1 equiv) and tert-butyl piperazine-1-carboxylate (91 mg, 0.486 mmol, 3 equiv) in DMSO (5 mL) was added DIEA (105 mg, 0.810 mmol, 5 equiv) dropwise at room temperature. The resulting mixture was stirred for 5 hr at 100 °C, then cooled to room temperature. The resulting mixture was purified by reverse flash chromatography (Condition 7, Gradient 1) to afford tert-butyl 4-[2-(6-methoxy-2,7-dimethylindazol-5- yl)pyrido[3,2-d]pyrimidin-6-yl]piperazine-1-carboxylate (51 mg, 64 %) as a solid. LCMS (ES, m/z): 490 [M+H] ⁺ . Synthesis of Compound 338 To a stirred solution of tert-butyl 4-[2-(6-methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2- d]pyrimidin-6-yl]piperazine-1-carboxylate (25 mg, 0.051 mmol, 1 equiv) in DCM (5 mL) was added boron tribromide (128 mg, 0.510 mmol, 10 equiv) dropwise at room temperature. The resulting mixture was stirred for 3 hr at room temperature, then concentrated under reduced pressure to give a residue. The residue was quenched with methanol at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by reverse flash chromatography (Condition 3, Gradient 4) to afford 2,7-dimethyl-5-[6- (piperazin-1-yl)pyrido[3,2-d]pyrimidin-2-yl]indazol-6-ol (13 mg, 68%) as a solid. LCMS (ES, m/z): 376 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 13.2λ (s, 1H), λ.25 (s, 1H), 8.85 (s, 1H), 8.40 (s, 1H), 8.18 (d, J = 9.5 Hz, 1H), 7.77 (d, J = 9.6 Hz, 1H), 4.14 (s, 3H), 3.73 (t, J = 5.0 Hz, 4H), 2.83 (dd, J = 6.2, 3.6 Hz, 4H), 2.40 (s, 3H). Example 132: Synthesis of Compound 342 Synthesis of Intermediate C75 To a stirred mixture of 5-{6-chloropyrido[3,2-d]pyrimidin-2-yl}-6-methoxy-2,7- dimethylindazole (55 mg, 0.162 mmol, 1 equiv) and tert-butyl piperazine-1-carboxylate (91 mg, 0.486 mmol, 3 equiv) in DMSO (5 mL) was added DIEA (105 mg, 0.810 mmol, 5 equiv) dropwise at room temperature. The resulting mixture was stirred for 3 hr at 100 °C, then cooled to room temperature. The resulting mixture was purified by reverse flash chromatography (Condition 7, Gradient 1) to afford tert-butyl 6-[2-(6-methoxy-2,7-dimethylindazol-5- yl)pyrido[3,2-d]pyrimidin-6-yl]-1,6-diazaspiro[3.4]octane-1- carboxylate (47 mg, 56%) as a solid. LCMS (ES, m/z): 516 [M+H] ⁺ . Synthesis of compound 342 To a stirred solution of tert-butyl 6-[2-(6-methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2- d]pyrimidin-6-yl]-1,6-diazaspiro[3.4]octane-1-carboxylate (25 mg, 0.048 mmol, 1 equiv) in DCM (5 mL) was added boron tribromide (122 mg, 0.480 mmol, 10 equiv) dropwise at room temperature. The resulting mixture was stirred for 3 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was quenched with methanol at room temperature. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by reverse flash chromatography (Condition 3, Gradient 4) to afford 5-(6- {1,6-diazaspiro[3.4]octan-6-yl}pyrido[3,2-d]pyrimidin-2-yl)- 2,7-dimethylindazol-6-ol (7 mg, 36%) as a solid. LCMS (ES, m/z): 402 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d6) δ 13.31 (s, 1H), 9.26 (s, 1H), 8.84 (s, 1H), 8.39 (s, 1H), 8.17 (d, J = 9.3 Hz, 1H), 7.40 (d, J = 9.4 Hz, 1H), 4.14 (s, 3H), 3.9 (s, 2H), 3.66 (d, J = 13.4 Hz, 4H), 2.40 (s, 3H), 2.19 (s, 2H).2.17 (s, 2H). Example 133: Synthesis of Compound 331, 332, and 393 Synthesis of Intermediate C76 To a stirred mixture of 5-bromo-3-fluoropyridin-2-amine (2 g, 10.471 mmol, 1.00 equiv) and 1- bromo-2,2-dimethoxypropane (2.3 g, 12.565 mmol, 1.2 equiv) in i-PrOH (20 mL) was added PPTS (0.26 g, 1.047 mmol, 0.1 equiv) in portions at room temperature. The resulting mixture was stirred for 16 h at 80 °C, then cooled to room temperature. The resulting mixture was diluted with water (20 mL) and adjusted to pH 9 with saturated aqueous NaHCO ₃ . A precipitate formed that was collected by filtration and dried in vacuum to afford 6-bromo-8- fluoro-2-methyl-1H,8aH-imidazo[1,2-a]pyridine (1.0 g, 41%) as a solid. LCMS (ES, m/z): 229 [M+H] ⁺ . Synthesis of Intermediate C77 To a stirred mixture of 6-bromo-8-fluoro-2-methylimidazo[1,2-a]pyridine (200 mg, 0.873 mmol, 1 equiv) and bis(pinacolato)diboron (244 mg, 0.960 mmol, 1.1 equiv) in dioxane (5 mL) was added KOAc (171 mg, 1.746 mmol, 2 equiv) and Pd(dppf)Cl ₂ (64 mg, 0.087 mmol, 0.1 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 hr at 100 °C under nitrogen atmosphere, then cooled to room temperature. To the resulting mixture was added 2-bromopyrido[3,2-d]pyrimidin-6-ol (237 mg, 1.048 mmol, 1.2 equiv), K3PO4 (371 mg, 1.746 mmol, 2 equiv), water (1 mL), and Pd(dppf)Cl ₂ (64 mg, 0.087 mmol, 0.1 equiv) in portions at room temperature. The resulting mixture was stirred for an additional 4 hr at 100 °C, then cooled to room temperature. The resulting mixture was diluted with ethyl acetate (10 mL) and water (10 mL). The resulting mixture was filtered, and the filter cake was washed with ethyl acetate (3 x 5 mL). The filtrate was concentrated under reduced pressure to afford 2- {8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl}pyrido[3,2-d]py rimidin-6-ol (250 mg, 97%) as a solid. LCMS (ES, m/z): 296 [M+H] ⁺ . Synthesis of Intermediate C78 A solution of 2-{8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl}pyrido[3,2-d] pyrimidin-6-ol (240 mg, 0.813 mmol, 1 equiv) in phosphorus oxychloride (10 mL) was stirred for 5 h at 110 °C, then cooled to room temperature. The resulting mixture was concentrated under vacuum to give a residue. The residue was basified to pH 8 with saturated NaHCO ₃ (aq.) and extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, washed with brine (1 x 10 mL), dried over anhydrous NaSO ₄ , and filtered. After filtration, the filtrate was concentrated under reduced pressure to afford 6-{6-chloropyrido[3,2-d]pyrimidin-2-yl}-8-fluoro-2-methylimi dazo[1,2- a]pyridine (120 mg, 47%) as a solid. LCMS (ES, m/z): 314 [M+H] ⁺ . Synthesis of Intermediate C79 To a stirred mixture of 6-{6-chloropyrido[3,2-d]pyrimidin-2-yl}-8-fluoro-2-methylimi dazo[1,2- a]pyridine (45 mg, 0.143 mmol, 1 equiv) and tert-butyl N-methyl-N-(pyrrolidin-3-yl)carbamate (58 mg, 0.286 mmol, 2 equiv) in DMSO (5 mL) was added DIEA (93 mg, 0.715 mmol, 5 equiv) dropwise at room temperature. The resulting mixture was stirred for 5 h at 100 °C, then cooled to room temperature and concentrated under reduced pressure to give a residue. The residue was purified by reverse flash chromatography(Condition 3, Gradient 5) to afford tert-butyl N-[1-(2- {8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl}pyrido[3,2-d]py rimidin-6-yl)pyrrolidin-3-yl]-N- methylcarbamate (38 mg, 55%) as a solid. LCMS (ES, m/z): 478 [M+H] ⁺ . A mixture of tert-butyl N-[1-(2-{8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl}pyrido[ 3,2- d]pyrimidin-6-yl)pyrrolidin-3-yl]-N-methylcarbamate (33 mg, 0.069 mmol, 1 equiv) in TFA (1 mL) and DCM (1 mL) was stirred for 2 hr at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was basified to pH 8 with 7 M NH ₃ (g) in methanol, then concentrated under vacuum to give a residue. The residue was purified by reverse flash chromatography (Condition 3, Gradient 5) to afford 1-(2-{8-fluoro-2- methylimidazo[1,2-a]pyridin-6-yl}pyrido[3,2-d]pyrimidin-6-yl )-N-methylpyrrolidin-3-amine (20 mg, 77%) as a solid. LCMS (ES, m/z): 378 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d6) δ λ.37 (s, 1H), 9.17 (s, 1H), 8.07 (d, J = 9.3 Hz, 1H), 8.01 (d, J = 3.1 Hz, 1H), 7.90 (d, J = 12.6 Hz, 1H), 7.38 (d, J = 9.4 Hz, 1H), 3.74-3.59 (m, 3H), 3.42 (s, 3H), 2.37 (d, J = 11.4 Hz, 6H), 2.12 (s, 1H), 1.90 (s, 1H). Synthesis of Compound 331 and 332 6-{2,8-dimethylimidazo[1,2-b]pyridazin-6-yl}-8-fluoro-2-(pyr rolidin-3-yl)isoquinolin-1-one (16.7 mg) was purified by chiral-HPLC (Condition 3, Gradient 2) to afford (R)-1-(2-(8-fluoro-2- methylimidazo[1,2-a]pyridin-6-yl)pyrido[3,2-d]pyrimidin-6-yl )-N-methylpyrrolidin-3-amine (4.7 mg, 28%) and (S)-1-(2-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)pyrido [3,2- d]pyrimidin-6-yl)-N-methylpyrrolidin-3-amine (4.7 mg, 28%) as solids. Compound 331： RT=2.359 min. LCMS (ES, m/z): 378 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d ₆ ) δ λ.37 (s, 1H), 9.17 (s, 1H), 8.07 (d, J = 9.3 Hz, 1H), 8.01 (d, J = 3.1 Hz, 1H), 7.90 (d, J = 12.6 Hz, 1H), 7.38 (d, J = 9.4 Hz, 1H), 3.74-3.59 (m, 3H), 3.42 (s, 3H), 2.37 (d, J = 11.4 Hz, 6H), 2.12 (s, 1H), 1.90 (s, 1H). Compound 332RT=3.251. LCMS (ES, m/z): 378 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d6) δ λ.37 (s, 1H), λ.17 (s, 1H), 8.07 (d, J = 9.3 Hz, 1H), 8.01 (d, J = 3.1 Hz, 1H), 7.90 (d, J = 12.6 Hz, 1H), 7.38 (d, J = 9.4 Hz, 1H), 3.74-3.59 (m, 3H), 3.42 (s, 3H), 2.37 (d, J = 11.4 Hz, 6H), 2.12 (s, 1H), 1.90 (s, 1H). Example 134: Synthesis of Compound 361 Synthesis of Intermediate C80 A solution of 2,6-dichloro-1,5-naphthyridine (3.15 g, 15.827 mmol, 1 equiv) in THF (60 mL) was treated with 2,2,6,6-Tetramethylpiperidinylmagnesium chloride lithium chloride complex solution in (1M) THF (19.18 g, 79.135 mmol, 5 equiv) for 0.5 h at -78°C under nitrogen atmosphere followed by the addition of acetaldehyde (1.39 g, 31.654 mmol, 2 equiv) dropwise at -78°C. The mixture was allowed to warm up to room temperature. The resulting mixture was extracted with water and ethyl acetate. The combined organic layers were dried over anhydrous Na ₂ SO4. 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 1-(2,6- dichloro-1,5- naphthyridin-4-yl)ethanol (0.72 g, 18%) as an oil. LCMS (ES, m/z): 243 [M+H] ⁺ Synthesis of Intermediate C81

A mixture of 1-(2,6-dichloro-1,5-naphthyridin-4-yl) ethanol (190 mg, 0.782 mmol, 1 equiv), 6- methoxy -2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl ) indazole (259.80 mg, 0.860 mmol, 1.1 equi v), Pd(dppf)Cl ₂ (5.72 mg, 0.008 mmol, 0.01 equiv) and K ₂ CO ₃ (216.04 mg, 1.564 mmol, 2 equiv) in dioxane (4 mL) and H ₂ O (0.4 mL) was stirred for 1h at 80°C under Nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE:EA = 3:1 to afford 1- [2-chloro-6-(6-methoxy-2,7-dimethylindazol-5-yl)-1,5-naphthy ridin-4-yl]ethanol (93 mg, 31%) as a solid. LCMS (ES, m/z): 383 [M+H] ⁺ Synthesis of Intermediate C82 A mixture of 1-[2-chloro-6-(6-methoxy-2,7-dimethylindazol-5-yl)-1,5-napht hyridin-4-yl]ethanol (90 mg, 0.235 mmol, 1 equiv), 1-[2-chloro-6-(6-methoxy-2,7-dimethylindazol-5-yl)-1,5- naphthyridin-4-yl]ethanol (90 mg, 0.235 mmol, 1 equiv), tert-butyl piperazine-1-carboxylate (52.54 mg, 0.282 mmol, 1.2 equiv), Pd ₂ (dba) ₃ (2.15 mg, 0.002 mmol, 0.01 equiv) and K ₂ CO ₃ (97.47 mg, 0.705 mmol, 3 equiv) in dioxane (2 mL) was stirred for 5h at 80°C under Nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE:EA = 1:1 to afford tert-butyl-4-[4- (1-hydroxyethyl)-6-(6-methoxy-2,7-dimethylindazol-5-yl)-1,5- naphthyridin-2-yl]piperazine-1- carboxylate (60 mg, 47%) as a solid. LCMS (ES, m/z): 533 [M+H] ⁺ Synthesis of Compound 361

A solution of tert-butyl 4-[4-(1-hydroxyethyl)-6-(6-methoxy-2,7-dimethylindazol-5-yl) -1,5- naphthyridin-2-yl]piperazine-1-carboxylate (60 mg, 0.113 mmol, 1 equiv) in H ₂ O (2 mL) was treated with HBr (0.2 mL, 6.847 mmol, 60.78 equiv) for 1 hr at 120°C. The residue was purified by Prep-TLC (Condition 1, Gradient 1) to afford 5-[8-(1-hydrox yethyl)-6-(piperazin-1-yl)-1,5- naphthyridin-2-yl]-2,7-dimethylindazol-6-ol (1.1 mg, 2%) as a solid. LCMS (ES, m/z): 419 [M+H] ^{+ 1} H NMR (300 MHz, DMSO-d6) δ 8.56 – 8.43 (m, 1H), 8.36 (s, 1H), 8.15 (d, J = 9.1 Hz, 1H), 7.60 (s, 1H), 5.54 (d, J = 5.5 Hz, 1H), 4.14 (s, 3H), 3.96 (d, J = 6.2 Hz, 4H), 2.39 (s, 7H), 1.54 (d, J = 6.0 Hz, 3H). Example 135: Synthesis of Compounds 318, 319, and 320 Synthesis of Intermediate C83 To a stirred solution of tert-butyl N-[1-(6-chloro-1,5-naphthyridin-2-yl) pyrrolidin-3-yl] -N- isopropyl carbamate (1 g, 2.558 mmol, 1 equiv) and Pd(PPh3)4 (0.59 g, 0.512 mmol, 0.2 equiv) in 1,4-dioxane (20 mL) were added hexamethyldistannan-1-ylidyne (1.68 g, 5.116 mmol, 2 equiv) dropwise for 2 hr at 100 °C under N ₂ atmosphere. The mixture was allowed to cool down to room temperature. The reaction was quenched with water at 0 °C. The resulting mixture was extracted with ethyl acetate (2 x 40mL). The combined organic layers were washed with water (3 x 40 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. This resulted in tert-butyl N-isopropyl-N-{1-[6-(trimethyl stannyl)-1,5 - naphthyridin-2-yl]pyrrolidin-3-yl}carbamate (1.2 g, 72%) as a solid. LCMS (ES, m/z): 521 [M+H] Synthesis of Intermediate C84

To a stirred solution of 5-bromo-6-(methoxymethoxy)-2,7-dimethylindazole (494.20 mg, 1.733 mmol, 1 equiv) and Pd(DtBPF)Cl ₂ (225.92 mg, 0.347 mmol, 0.2 equiv) in dioxane (20 mL) was added tert-butyl N-isopropyl-N-{1-[6-(trimethylstannyl)-1,5-naphthyridin-2-yl ]pyrrolidin-3- yl}carbamate (900 mg, 1.733 mmol, 1 equiv) dropwise for 2 hr at 100 °C under N ₂ atmosphere. The mixture was allowed to cool down to room temperature. The resulting mixture was diluted with water (30 mL). The resulting mixture was extracted with ethylacetate (3 x 40mL). The combined organic layers were washed with water (3 x 20 mL), dried over anhydrous Na ₂ SO ₄ . 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 tert-butyl N-isopropyl-N- (1-{6-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]-1,5-naph thyridin-2-yl}pyrrolidin-3- yl)carbamate (300 mg, 30%) as a solid. LCMS (ES, m/z): 561 [M+H] To a stirred solution of 5-{6-[3-(isopropylamino) pyrrolidin-1-yl]-1,5-naphthyridin-2-yl} -2,7- dimethy lindazol-6-ol (260 mg, 0.624 mmol, 1 equiv)in 1,4-dioxane (30 mL)were added HCl(gas)in 1,4-dioxane (20 mL, 658.238 mmol, 1419.51 equiv) in portions for 6h at room temperature. The resulting mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC (Condition 1, Gradient 28) to afford 5-{6-[3- (isopropylamino)pyrrolidin -1-yl]-1,5-naphthyridin -2-yl}-2,7-dimethylindazol-6-ol (42 mg, 21%) as a solid. LCMS (ES, m/z): 417 [M+H] Synthesis of Compounds 319 and 32- The crude product (5-{6-[3-(isopropylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2 -yl}-2,7- dimethylindazol-6-ol (100 mg, 0.240 mmol, 1 equiv) was purified by CHIRAL-HPLC (Condition 4, Gradient 3) to afford (48.5 mg, 48%) and (49.5 mg, 49%) as solid. Analysis data Example 136: Synthesis of Compounds 328, 329, and 330 Synthesis of Intermediate C85 To a stirred solution of 6-bromo-4-fluoro-5-methoxy-2-methyl-1,3-benzoxazole (500 mg, 1.923 mmol, 1 equiv) and Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (313.24 mg, 0.385 mmol, 0.2 equiv) in 1,4-dioxane (20 mL) were added K3PO4 (1224.31 mg, 5.769 mmol, 3 equiv) and bis(pinacolato)diboron (976.46 mg, 3.846 mmol, 2 equiv) in portions at room temperature. A solution was stirred for 24 hr at 100 °C under N ₂ atmosphere. The mixture was allowed to cool down to room temperature. The resulting mixture was extracted with ethyl acetate (2 x 30 mL). The combined organic layers were washed with water (3 x 30 mL), dried over anhydrous Na ₂ SO4. After filtration, the filtrate was concentrated under reduced pressure. This resulted in 4-fluoro-5-methoxy-2-methyl-6- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol e (950 mg, 72%) as an oil. LCMS (ES, m/z): 308 [M+H] Synthesis of Intermediate C86 To a stirred solution of tert-butyl N-[1-(6-chloro-1,5-na phthyridin-2-yl)pyrrolidin-3-yl]- N- isopropylc arbamate (900 mg, 2.302 mmol, 1 equiv) and 4-fluoro-5-methoxy-2-me thyl-6- (4,4,5,5-tetramethyl-1, 3,2-d ioxaborolan-2-yl)-1,3-benzoxazole (1.06 g, 3.453 mmol, 1.5 equiv) and Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (375.10 mg, 0.460 mmol, 0.2 equiv) in 1,4-dioxane (16 mL) and H ₂ O (4 mL) were added K3PO4 (1.46 g, 6.906 mmol, 3 equiv) dropwise at room temperature. A mixture was stirred for 2 hr at 100 °C under N ₂ atmosphere. The mixture was allowed to cool down to room temperature. The reaction was quenched with water at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The combined organic layers were washed with water (1 x 30 mL), dried over anhydrous Na ₂ SO ₄ . 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 tert-butyl N-{1-[6-(4-fluoro-5-methoxy-2- methyl -1,3-benzoxazol-6-yl)-1,5-naphthyridin-2-yl] pyrrolidi n-3-yl}-N-isopropylcarbamate (420 mg, 34%) as a solid. LCMS (ES, m/z): 536 [M+H] Synthesis of Compound 328 To a stirred solution of 4-fluoro-6-{6-[3-(isopropylamino)py rrolidin-1-yl]-1,5-naphthyri din-2-yl}-2-m ethyl-1,3-benzoxazol-5-ol (380 mg, 0.902 mmol, 1 equiv) in DCM (30 mL) were added BBr3 (1.12 g, 4.510 mmol, 5 equiv) in portions for 4 days at room temperature. The reaction was quenched by the addition of methanol (10 mL) at 0 °C. The resulting mixture was concentrated under reduced pressure. The resulting mixture was extracted with ethyl acetate (1 x 30 mL). The combined organic layers were washed with water (3 x 20 mL), dried over anhydrous Na ₂ SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC (Condition 1, Gradient 24) to afford tert-butyl N-{1- [6-(4-fluoro-5-met hoxy-2-methyl-1,3-benzoxazol-6 -yl) -1,5-naphthyridin-2-yl]pyrrolidin-3-yl}- N-isopropylcarbamate (33.7 mg, 6%) as a solid. LCMS (ES, m/z): 422 [M+H] Synthesis of Compounds 329 and 330 The crude product (4-flu oro-6-{6-[3- (isopropylamino) pyrrolidin-1-yl] -1,5-naphthyr idin-2-yl} -2-met hyl-1,3-benzoxazol-5-ol (120 mg, 0.285 mmol, 1 equiv) was purified by Prep-HPLC (Condition 4, Gradient 4) to afford (48.1 mg, 40%) and (48.3 mg, 40%) as solids. Analysis data

Example 137: Synthesis of Compounds 401 and 402 Synthesis of Intermediate C87 To a stirred solution of 5-methoxy-2,4-dimethyl-6-(4,4,5,5-tetr amethyl-1,3,2-dioxabo rolan-2- yl)-1,3-benzoxazole (300 mg, 0.990 mmol, 1 equiv) and tert-butyl N-[1-(6-chloro-1,5-n aphthyridin-2 -yl) pyrrolidin-3-yl]-N-isopropylcarbamate (580.23 mg, 1.485 mmol, 1.5 equiv) in dioxane (16 mL) and H ₂ O (4 mL) were added Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (80.61 mg, 0.099 mmol, 0.1 equiv) and K3PO4 (630.14 mg, 2.970 mmol, 3 equiv) in portions at room temperature.A mixture was stirred for 2 hr at 100 °C under N2 atmosphere. The mixture was allowed to cool down to room temperature.The reaction was quenched with water at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 20mL). The combined organic layers were washed with water (3 x 20 mL), dried over anhydrous Na ₂ SO ₄ . 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 tert-butyl N-isopropyl-N-{1-[6-(5-methoxy- 2,4- di me thyl-1,3-benzoxazol-6-yl)-1,5-naphthyridin- 2-y l]pyrroledin-3-yl}carbamate (310 mg, 58%) as a solid. LCMS (ES, m/z): 532 [M+H] Synthesis of Intermediate C88

Into a 20 mL 4-necked round-bottom flask were added tert-butyl N-isopropyl-N-{1-[6-(5- methoxy-2,4-dimethyl-1,3-benzoxazol-6-yl)-1,5-naphthyridin-2 -yl]pyrrolidin-3-yl}carbamate (280 mg, 0.527 mmol, 1 equiv) and DCM (6 mL) at room temperature. To the above mixture was added BBr3 (1319.38 mg, 5.270 mmol, 10 equiv) dropwise over 10 min at 0 °C. The resulting mixture was stirred for additional 3days at room temperature. The reaction was quenched by the addition of methanol (3 mL) at 0 °C.The resulting mixture was extracted with ethyl acetate (1 x 20 mL). The combined organic layers were washed with water (3 x 10 mL), dried over anhydrous Na ₂ SO4. After filtration, the filtrate was concentrated under reduced pressure.The crude product was purified by Prep-HPLC (Condition 1, Gradient 29) to afford 6- {6-[3-(isopropylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2-yl }-2,4-dimethyl-1,3-benzoxazol-5- ol (45.2 mg, 20%) as a solid. LCMS (ES, m/z): 418 [M+H] The 6-{6-[3-(isopropylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2- yl}-2,4-dimethyl-1,3- benzoxazol-5-ol (110 mg, 0.263 mmol, 1 equiv) was purified by Chiral-Prep-HPLC (Condition 4, Gradient 4) to afford 6-{6-[(3S)-3-(isopropylamino)pyrrolidin-1-yl]-1,5-naphthyrid in-2-yl}- 2,4-dimethyl-1,3-benzoxazol-5-ol (36.4 mg, 33.09%) and 6-{6-[(3R)-3- (isopropylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2-yl}-2,4- dimethyl-1,3-benzoxazol-5-ol (36.8 mg, 33%) as a solid. Analysis data

Example 138: Synthesis of Compound 346 Synthesis of Intermediate C89 Into a 40mL round-bottom flask were added 6-bromo-2-ethyl-5-methoxy-1,3-benzoxazole (200 mg, 0.781 mmol, 1 equiv) and bis(pinacolato)diboron (397 mg, 1.562 mmol, 2 equiv) at room temperature. To the above mixture was added potassium acetate (230 mg, 2.343 mmol, 3 equiv) and Pd(dppf)Cl ₂ (64 mg, 0.078 mmol, 0.1 equiv) in portions over 10 min at room temperature. The resulting mixture was stirred for additional 24 hr at 80 °C. The mixture was allowed to cool down to room temperature. The resulting mixture was extracted with ethyl acetate (2 x 30 mL). The combined organic layers were washed with water (3 x 30 mL), dried over anhydrous Na ₂ SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EA (5:1) to afford 2-ethyl-5- methoxy -6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxa zole (650 mg, 96%) as a solid. LCMS (ES, m/z): 304 [M+H] Synthesis of Intermediate C90 To a stirred solution of N-tert-butyl-1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3- amine (620 mg, 2.034 mmol, 1 equiv) and Pd(DtBPF)Cl ₂ (133 mg, 0.203 mmol, 0.1 equiv) in 1,4- dioxane (16 mL) and H ₂ O (4 mL) were added 2-ethyl-5-methoxy-6-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1,3-benzoxazole (925 mg, 3.051 mmol, 1.5 equiv) and K ₃ PO ₄ (1.29 g, 6.102 mmol, 3 equiv) dropwise at room temperature under N ₂ atmosphere. The mixture was stirred for 2h at 80 °C under N2 atmosphere. The mixture was allowed to cool down to room temperature. The resulting mixture was extracted with EA (2 x 30 mL). The combined organic layers were washed with water (3 x 20 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:3) to afford N-tert-butyl-1-[6-(2-ethyl-5-methoxy -1,3- benzoxazol-6-yl) -1,5-naphthyridin-2-yl]pyrrolidin-3-amine (25 mg, 2%) as an oil. LCMS (ES, m/z): 446 [M+H] Synthesis of Compound 346

To a stirred solution of N-tert-butyl-1-[6-(2-ethyl-5-methoxy-1,3-benzoxazol-6-yl)-1, 5- naphtha yridin-2-yl]pyrrolidin-3-amine (20 mg, 0.045 mmol, 1 equiv) in DCM (5 mL) was added BBr ₃ (225 mg, 0.900 mmol, 20 equiv) dropwise at 0 °C. The mixture was stirred for 3 days at room temperature. The mixture was basified to pH 8 with saturated NaHCO ₃ . The resulting mixture was extracted with CH ₂ Cl ₂ (3 x 30 mL). The combined organic layers were washed with water (3 x 20 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC (Condition 3, Gradient 24) to afford 6-{6-[3-(tert-butylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2 -yl}-2-ethyl-1,3-benzoxazol- 5-ol (7 mg, 36%) as a solid. LCMS (ES, m/z): 432 [M+H] ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.53 (s, 1H), 8.45 – 8.38 (m, 2H), 8.15 – 8.05 (m, 2H), 7.15 (d, J = 11.6 Hz, 2H), 3.91 – 3.80 (m, 1H), 3.79 – 3.72 (m, 1H), 3.49 (dd, J = 18.8, 9.9 Hz, 2H), 3.21 – 3.05 (m, 1H), 2.96 (q, J = 7.5 Hz, 2H), 2.24 – 2.08 (m, 1H), 1.84 – 1.69 (s, 2H), 1.35 (t, J = 7.5 Hz, 3H), 1.10 (s, 9H). Example 139: Synthesis of Compounds 334 and 336 Synthesis of Intermediate C91 To a stirred solution of 6-bromo-5-methoxy-2-(methoxymethyl)-1,3-benzoxazole (250 mg, 0.919 mmol, 1 equiv) and Pd(dppf)Cl ₂ (75 mg, 0.092 mmol, 0.1 equiv) in dioxane (20 mg) were added bis(pinacolato)diboron (467 mg, 1.838 mmol, 2 equiv) and potassium acetate (271 mg, 2.757 mmol, 3 equiv) in portions at room temperature. The mixture was stirred for 24 hr at 80 °C under N ₂ atmosphere. The mixture was allowed to cool down to room temperature. The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The combined organic layers were washed with water (2 x 30 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. This resulted in 5-methoxy-2-(methoxymethyl)-6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazole (630 mg, 75%) as a solid. LCMS (ES, m/z): 320 [M+H] Synthesis of Intermediate C92 To a stirred solution of 5-methoxy-2-(methoxymethyl)-6-(4,4,5,5-tetramethyl-1,3,2-dio xaborolan -2-yl)-1,3-benzoxazole (630 mg, 1.974 mmol, 1 equiv) and Pd(dppf)Cl ₂ (161 mg, 0.197 mmol, 0.1 equiv) in 1,4-dioxane (16 mL) and H ₂ O (4 mL) were added N-tert-butyl-1-(6-chloro-1,5- naphthyridin-2-yl) pyrrolidin-3-amine (902 mg, 2.961 mmol, 1.5 equiv) and K3PO4 (1.26 g, 5.922 mmol, 3 equiv) dropwise at room temperature. The mixture was stirred for 2 h at 90 °C under N ₂ atmosphere. The mixture was allowed to cool down to room temperature. The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The combined organic layers were washed with water (2 x 30 mL), dried over anhydrous Na ₂ SO4. 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 N-tert-butyl-1-{6-[5-methoxy-2- (methoxymethyl) -1,3-benzoxazol-6-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-ami ne (320 mg, 35%) as a solid. LCMS (ES, m/z): 462 [M+H] Synthesis of Compounds 334 and 336 To a stirred solution of N-tert-butyl -1-{6-[5-methoxy -2-(methoxymethyl) -1,3-benzoxazol-6-yl] -1,5-naphthyridin-2-yl}pyrrolidin-3-amine (290 mg, 0.628 mmol, 1 equiv) in DCM (20 mL) were added BBr ₃ (1.57 g, 6.280 mmol, 10 equiv) dropwise at 0°C. The mixture was stirred for 3 days at room temperature. The crude product was purified by Prep-HPLC (Condition 1, Gradient 18) to afford 6-{6-[3-(tert-butylamino) pyrrolidin-1-yl] -1,5-naphthyr idin-2-yl} -2- (methoxymethyl)-1,3-benzoxazol-5-ol (9.6 mg, 3%) and 6-{6-[3-(tert-butylamino)p yrrolid in-1- yl] -1,5-naphthyridin-2-yl}-2-(hydroxymethyl)-1,3-benzoxazol-5-o l (14.8 mg, 5%) as a solid. LCMS (ES, m/z): 448 [M+H] LCMS (ES, m/z): 434 [M+H] Example 140: Synthesis of Compounds 378 and 379 Synthesis of Intermediates C93 and C94 A solution of 1-(6-chloro-1,5-naphthyridin-2-yl)-N-[1-(fluoromethyl)cyclop ropyl]pyrrolidin-3- amine (300 mg, 0.935 mmol, 1 equiv) and 5-(methoxymethoxy)-2,4-dimethyl-6-(4,4,5,5- tetramethyl -1,3,2-dioxaborolan-2-yl)-1,3-benzoxazole (373.90 mg, 1.122 mmol, 1.2 equiv) in dioxane (6 ml)/H ₂ O (1.2 mL) was treated with Pd(dppf)Cl ₂ (76.5 mg, 0.0935 mmol, 0.1 equiv) under nitrogen atmosphere followed by the addition of K ₃ PO ₄ (595.51 mg, 2.805 mmol, 3 equiv) in portions at room temperature. The mixture was stirred for 2 hr at 80 °C. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:1) to afford 156 mg crude. The crude product (156mg) was purified by Prep-CHIRAL-HPLC with the following conditions (Condition 5, Gradient 1) to afford (3S)-N-[1- (fluoromethyl)cyclopropyl]-1-{6-[5- (methoxymethoxy)-2,4-dimethyl-1,3-benzoxazol -6-yl]-1,5- naphthyridin-2-yl}pyrrolidin-3-amine (55 mg, 11%) as a solid and (3R)-N-[1- (fluoromethyl)cyclopropyl]-1-{6-[5-(methoxymethoxy)-2,4-dime thyl-1,3-benzoxazol-6-yl]-1,5- naphthyridin-2-yl}yrrolidin-3-amine (50 mg, 10%) as a solid. Synthesis of Compound 378 A mixture of (3S)-N-[1-(fluoromethyl)cyclopropyl]-1-{6-[5-(methoxymethoxy )-2,4-dimethyl - 1,3-benzoxazol-6-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-amin e (55 mg, 0.112 mmol, 1 equiv) and HCl(gas)in 1,4-dioxane (1 mL) in methanol (1 mL) was stirred for 2 hr at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under vacuum. The crude product (55mg) was purified by Prep-HPLC (Condition 1, Gradient 30) to afford 6-{6-[(3S)-3- {[1-(fluoromethyl)cyclopropyl]amino}pyrrolidin-1-yl]-1,5-nap hthyridin-2-yl}-2,4-dimethyl-1,3- benzoxazol-5-ol (23 mg, 45%) as a solid. LCMS (ES, m/z): 448 [M+H] + ¹ H NMR (400 MHz, DMSO-d6) δ 14.λ8 (s, 1H), 8.41 (d, J = 9.3 Hz, 1H), 8.25 (s, 1H), 8.14 (dd, J = 9.3, 0.8 Hz, 1H), 8.08 (dd, J = 9.1, 0.8 Hz, 1H), 7.15 (d, J = 9.3 Hz, 1H), 4.47 (s, 1H), 4.34 (s, 1H), 3.78 (s, 1H), 3.79 – 3.67 (m, 2H), 3.55 (t, J = 8.3 Hz, 1H), 2.75 – 2.64 (m, 1H), 2.61 (s, 3H), 2.40 (s, 3H), 2.14 (dt, J = 12.5, 6.3 Hz, 1H), 1.89 (dd, J = 12.4, 6.6 Hz, 1H), 0.62 (d, J = 3.1 Hz, 4H). Synthesis of Compound 379 A mixture of (3R)-N-[1-(fluoromethyl)cyclopropyl]-1-{6-[5-(methoxymethoxy )-2,4-dimethyl - 1,3-benzoxazol-6-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-amin e (50 mg, 0.102 mmol, 1 equiv) and HCl(gas)in 1,4-dioxane (1 mL) in MeOH (1 mL) was stirred for 2h at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under vacuum. The crude product (50mg) was purified by Prep-HPLC (Condition 1, Gradient 30) to afford 6-{6-[(3R)-3- {[1-(fluoromethyl)cyclopropyl]amino}pyrrolidin-1-yl]-1,5-nap hthyridin-2-yl}-2,4-dimethyl-1,3- benzoxazol-5-ol (14.1 mg, 30%) as a solid. LCMS (ES, m/z): 448 [M+H] + ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.λ8 (s, 1H), 8.41 (d, J = 9.3 Hz, 1H), 8.25 (s, 1H), 8.13 (dd, J = 9.3, 0.8 Hz, 1H), 8.08 (d, J = 9.1 Hz, 1H), 7.15 (d, J = 9.3 Hz, 1H), 4.47 (s, 1H), 4.34 (s, 1H), 3.77 (d, J = 9.5 Hz, 1H), 3.70 (s, 2H), 3.65 (s, 1H), 3.54 (d, J = 9.4 Hz, 1H), 2.70 (s, 1H), 2.61 (s, 3H), 2.40 (s, 3H), 2.14 (dq, J = 12.6, 6.3 Hz, 1H), 1.89 (dd, J = 12.5, 6.5 Hz, 1H), 0.62 (d, J = 3.7 Hz, 4H). Example 141: Synthesis of Compounds 391 and 392 Synthesis of Intermediate C95 To a solution of N-tert-butyl-1-[6-(trimethylstannyl)-1,5-naphthyridin-2-yl]p yrrolidin-3-amine (1.5 g, 3.463 mmol, 1 equiv) and 5-bromo-7-fluoro-6-(methoxymethoxy)-2-methylindazole (1.00 g, 3.463 mmol, 1 equiv) in 1,4-dioxane (20 mL)were added Pd(DtBPF)Cl ₂ (0.23 g, 0.346 mmol, 0.1 equiv) . After stirring for 3 h at 100°C under a nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with DCM / MeOH (10:1) to afford N-tert-butyl-1-{6-[7-fluoro-6- (methoxymethoxy)-2-methylindazol-5-yl]-1,5-naphthyridin-2-yl }pyrrolidin-3-amine (500 mg, 30%) as a solid. Synthesis of Compounds 391 and 392 To a solution of N-tert-butyl-1-{6-[7-fluoro-6-(methoxymethoxy)-2-methylindaz ol-5-yl]-1,5- naphthyridin-2-yl}pyrrolidin-3-amine (500 mg, 1.045 mmol, 1 equiv) in MeOH (5 mL) were added HCl(gas)in 1,4-dioxane (5 mL) . After stirring for 2 h at 25°C under a nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure. The crude product was purified by Chiral-Prep-HPLC (Condition 4, Gradient 4) to afford the crude product. The crude product was purified by Chiral-Prep-HPLC (Condition 3, Gradient 21) to afford 5-{6- [(3S)-3-(tert-butylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2 -yl}-7-fluoro -2-methylindazol-6-ol (27.7 mg, 6.1%) as a solid, 5-{6-[(3R)-3-(tert-butylamino)pyrrolidin-1-yl] -1,5-naphthyridin-2- yl}-7-fluoro-2-methylindazol-6-ol (67.7 mg, 15%) as a solid.

Example 142: Synthesis of Compounds 372 and 373 Synthesis of Intermediates C96 and C97 A solution of 1-(6-chloro-1,5-naphthyridin-2-yl)-N-[1-(fluoromethyl)cyclop ropyl]pyrrolidin-3- amine (300 mg, 0.935 mmol, 1 equiv) and 4-fluoro-5-(methoxymethoxy)-2-methyl-6-(4,4,5,5- tetramethyl -1,3,2-dioxaborolan-2-yl)-1,3-benzoxazole (378.35 mg, 1.122 mmol, 1.2 equiv) in dioxane (1.2 mL) and H ₂ O (6 mL) was treated with Pd(dtbpf)Cl ₂ (60.95 mg, 0.094 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere followed by the addition of K3PO4 (390.56 mg, 2.805 mmol, 3 equiv) in portions at room temperature. The mixture was stirred for 2 hr at 80 °C. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ /MeOH (10:1) to afford 1-{6-[4-fluoro-5-(methoxymethoxy)-2-methyl-1,3- benzoxazol-6-yl]-1,5-naphthyridin-2-yl}-N-[1-(fluoromethyl)c yclopropyl]pyrrolidin-3-amine (200 mg) as a brown solid. The crude product (200mg) was purified by Prep-CHIRAL-HPLC (Condition 4, Gradient 1) to afford (3R)-1-{6-[4-fluoro-5-(methoxymethoxy)-2-methyl-1,3- benzoxazol-6-yl]-1,5-naphthyridin-2-yl}-N-[1-(fluoromethyl)c yclopropyl]pyrrolidin-3-amine (60 mg, 12%) as a solid and (3S)-1-{6-[4-fluoro-5-(methoxymethoxy)-2-methyl-1,3-benzoxaz ol- 6-yl]-1,5-naphthyridin-2-yl}-N-[1-(fluoromethyl)cyclopropyl] pyrrolidin-3-amine (55 mg, 11%) as a solid. Synthesis of Compound 372 A mixture of (3R)-1-{6-[4-fluoro-5-(methoxymethoxy)-2-methyl-1,3-benzoxaz ol-6-yl]-1,5- naphthyridin -2-yl}-N-[1-(fluoromethyl)cyclopropyl]pyrrolidin-3-amine (60 mg, 0.121 mmol, 1 equiv) and HCl(gas)in 1,4-dioxane (1 mL) in MeOH (1 mL) was stirred for 2h at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under vacuum. The crude product (55mg) was purified by Prep-HPLC (Condition 1, Gradient 31) to afford 4- fluoro-6-{6-[(3R)-3-{[1-(fluoromethyl)cyclopropyl]amino}pyrr olidin-1-yl]-1,5-naphthyridin-2- yl}-2-methyl-1,3-benzoxazol-5-ol (17.6 mg, 32%) as a solid. LCMS (ES, m/z): 452 [M+H] + ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 15.06 (s, 1H), 8.44 (d, J = 9.2 Hz, 1H), 8.32 (d, J = 1.3 Hz, 1H), 8.13 (ddd, J = 19.0, 9.2, 0.8 Hz, 2H), 7.17 (d, J = 9.3 Hz, 1H), 4.47 (s, 1H), 4.34 (s, 1H), 3.77 (d, J = 9.2 Hz, 1H), 3.70 (s, 2H), 3.54 (d, J = 9.4 Hz, 1H), 3.34 (s, 1H),2.71 (d, J = 4.1 Hz, 1H), 2.64 (s, 3H), 2.14 (dq, J = 12.6, 6.3 Hz, 1H), 1.94 – 1.86 (m, 1H), 0.62 (d, J = 4.6 Hz, 4H). Synthesis of Compound 373 A mixture of (3S)-1-{6-[4-fluoro-5-(methoxymethoxy)-2-methyl-1,3-benzoxaz ol-6-yl]-1,5- naphthyridin -2-yl}-N-[1-(fluoromethyl)cyclopropyl]pyrrolidin-3-amine (55 mg, 0.111 mmol, 1 equiv) and HCl(gas)in 1,4-dioxane (1 mL) in MeOH (1 mL) was stirred for 2h at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under vacuum. The crude product (50mg) was purified by Prep-HPLC (Condition 1, Gradient 32) to afford 4- fluoro-6-{6-[(3S)-3-{[1-(fluoromethyl)cyclopropyl]amino}pyrr olidin-1-yl]-1,5-naphthyridin-2- yl}-2-methyl-1,3-benzoxazol-5-ol (9.6 mg, 19%) as a solid. LCMS (ES, m/z): 452 [M+H] + ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 15.06 (s, 1H), 8.44 (d, J = 9.2 Hz, 1H), 8.32 (d, J = 1.4 Hz, 1H), 8.13 (dd, J = 19.1, 9.2 Hz, 2H), 7.17 (d, J = 9.3 Hz, 1H), 4.47 (s, 1H), 4.34 (s, 1H), 3.78 (s, 1H), 3.70 (s, 2H), 3.54 (d, J = 9.3 Hz, 1H), 3.31 (s, 1H), 2.71 (d, J = 4.2 Hz, 1H), 2.64 (s, 3H), 2.14 (dt, J = 12.4, 6.3 Hz, 1H), 1.90 (s, 1H), 0.62 (d, J = 4.5 Hz, 4H). Example 143: Synthesis of Compounds 368 and 369 Synthesis of Intermediate C98 A solution of 2-bromopyrido[3,2-d]pyrimidin-6-ol (450 mg, 1.991 mmol, 1 equiv) in dioxane (1.4 mL) and H ₂ O (9 mL) was treated with Pd(dppf)Cl ₂ (162.18 mg, 0.199 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere followed by the addition of K3PO4 (1267.77 mg, 5.973 mmol, 3 equiv) in portions at room temperature. The mixture was stirred for 2 hr at 80 °C. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ /MeOH (10:1) to afford 2-(6-methoxy-2,7-dimethylindazol-5-yl) pyrido[3,2- d]pyrimidin-6-ol (400 mg, 62%) as a solid. Synthesis of Intermediate C99 and C100 A solution of 2-(6-methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2-d]pyrimidin -6-ol (390 mg, 1.214 mmol, 1 equiv) in acetonitrile (252.62 mL) was treated with BOP (1073.58 mg, 2.428 mmol, 2 equiv) at room temperature under nitrogen atmosphere followed by the addition of DBU (554.31 mg, 3.642 mmol, 3 equiv) dropwise at room temperature. The mixture was stirred for 2 hr at room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by reverse flash chromatography (Condition 7, Gradient 3) to afford 180 mg product as a solid. The crude product was purified by Prep-chiral-HPLC (Condition 4, Gradient 5) to afford tert-butyl N-[(3R)-1-[2-(6-methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2- d]pyrimidin-6- yl]pyrrolidin-3-yl]-N-methylcarbamate (70 mg, 11%) as a solid and tert-butyl N-[(3S)-1-[2-(6- methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2-d]pyrimidin -6-yl]pyrrolidin-3-yl]-N- methylcarbamate (80 mg, 13%) as a solid. Synthesis of Compound 369 A mixture of tert-butyl N-[(3S)-1-[2-(6-methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2- d]pyrimidin-6-yl] pyrrolidin-3-yl]-N-methylcarbamate (70 mg, 0.139 mmol, 1 equiv) and BBr3 (0.5 mL, 5.289 mmol, 38.05 equiv) in dichloromethane (2 mL, 31.461 mmol, 226.34 equiv) was stirred for 1 day at room temperature under nitrogen atmosphere. The reaction was quenched with methanol at 0 °C. The resulting mixture was concentrated under vacuum. The crude product was purified by Prep-HPLC (Condition 1, Gradient 2) to afford 2,7-dimethyl-5-{6-[(3S)-3- (methylamino) pyrrolidin-1-yl]pyrido[3,2-d]pyrimidin-2-yl}indazol-6-ol (30.6 mg, 56%) as a solid. LCMS (ES, m/z): 390 [M+H] + ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.31 (s, 1H), λ.25 (d, J = 0.8 Hz, 1H), 8.84 (d, J = 0.8 Hz, 1H), 8.38 (s, 1H), 8.16 (dd, J = 9.4, 0.8 Hz, 1H), 7.41 (d, J = 9.4 Hz, 1H), 4.13 (s, 3H), 3.72 (dd, J = 11.1, 5.8 Hz, 1H), 3.67 (s, 2H), 3.62 (s, 1H), 3.43 (s, 1H), 2.39 (d, J = 0.7 Hz, 3H), 2.33 (s, 3H), 2.11 (dt, J = 12.9, 6.4 Hz, 2H), 1.89 (s, 1H). Synthesis of Compound 368 A solution of tert-butyl N-[(3R)-1-[2-(6-methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2- d]pyrimidin -6-yl]pyrrolidin-3-yl]-N-methylcarbamate (80 mg, 0.159 mmol, 1 equiv) and BBr3 (0.5 mL, 5.289 mmol, 33.29 equiv) in DCM (2 mL) was stirred for 1days at room temperature under nitrogen atmosphere. The reaction was quenched with MeOH at 0°C. The resulting mixture was concentrated under vacuum. The crude product was purified by Prep-HPLC (Condition 1, Gradient 2) to afford 2,7-dimethyl-5-{6-[(3R)-3-(methylamino)pyrrolidin-1- yl]pyrido[3,2-d]pyrimidin -2-yl}indazol-6-ol (29.6 mg, 47%) as a solid. LCMS (ES, m/z): 390 [M+H] + ¹ H NMR (400 MHz, DMSO-d6) δ 13.31 (s, 1H), λ.25 (d, J = 0.8 Hz, 1H), 8.84 (d, J = 0.8 Hz, 1H), 8.38 (s, 1H), 8.16 (dd, J = 9.4, 0.8 Hz, 1H), 7.41 (d, J = 9.4 Hz, 1H), 4.13 (s, 3H), 3.72 (dd, J = 11.1, 5.8 Hz, 1H), 3.67 (s, 2H), 3.62 (s, 1H), 3.43 (s, 1H), 2.39 (d, J = 0.7 Hz, 3H), 2.33 (s, 3H), 2.11 (dt, J = 12.9, 6.4 Hz, 1H), 1.89 (s, 2H). Example 144: Synthesis of Compounds 380 and 381 Synthesis of Intermediate C101 A mixture of 2-bromopyrido[3,2-d]pyrimidin-6-ol (300 mg, 1.327 mmol, 1 equiv) and 7-fluoro- 6-methoxy-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan -2-yl)indazole (487.59 mg, 1.592 mmol, 1.2 equiv) and Pd(dppf)Cl ₂ (97.12 mg, 0.133 mmol, 0.1 equiv) and K3PO4(845.18 mg, 3.981 mmol, 3 equiv) in dioxane (6 mL) and H ₂ O (1.2 mL) was stirred for 2 hr at 80 °C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ /MeOH (10:1) to afford 2-(7-fluoro-6-methoxy-2- methylindazol-5-yl)pyrido[3,2-d]pyrimidin-6-ol (150 mg, 34%) as a solid. Synthesis of Intermediate C102 A mixture of 2-(7-fluoro-6-methoxy-2-methylindazol-5-yl)pyrido[3,2-d]pyri midin-6-ol (150 mg, 0.461 mmol, 1 equiv) and tert-butyl N-(pyrrolidin-3-yl)carbamate (103.06 mg, 0.553 mmol, 1.2 equiv) and (1H-1,2,3-benzotriazol-1-yloxy)tris(pyrrolidin-1-yl)phosphan ium; hexafluoro-l^[5]- phosphanuide (479.91 mg, 0.922 mmol, 2 equiv) and DIEA (178.79 mg, 1.383 mmol, 3 equiv) in DMF (3 mL) was stirred for 2 hr at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under vacuum. The residue was purified by reverse flash chromatography (Condition 8, Gradient 1) to afford tert-butyl N-{1-[2-(7-fluoro-6-methoxy-2- methylindazol-5-yl)pyrido[3,2-d]pyrimidin-6-yl] pyrrolidin-3-yl}carbamate (150 mg, 65%) as a solid. Synthesis of Compounds 380 and 381 A mixture of 5-[6-(3-aminopyrrolidin-1-yl)pyrido[3,2-d]pyrimidin-2-yl]-7- fluoro-2- methylindazol-6-ol (150 mg, 0.395 mmol, 1 equiv) and boron tribromide (1 mL, 0.004 mmol, 0.01 equiv) in DCE (3 mL) was stirred for 1 day at 60 °C under nitrogen atmosphere. The reaction was quenched with methanol at 0°C. The resulting mixture was concentrated under vacuum. The crude product (150mg) was purified by Prep-HPLC (Condition 1, Gradient 2) to afford 70 mg crude product. The product was then purified by chiral-Prep-HPLC (Condition 6, Gradient 1) to afford 5-{6-[(3R)-3-aminopyrrolidin-1-yl]pyrido[3,2-d]pyrimidin-2-y l}-7-fluoro- 2-methylindazol-6-ol (4.3 mg, 2%) as a solid and 5-{6-[(3S)-3-aminopyrrolidin-1-yl]pyrido[3,2- d]pyrimidin-2-yl} -7-fluoro-2-methylindazol-6-ol (1 mg, 1%) as a solid. LCMS (ES, m/z): 380 [M+H] + ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.35 (s, 1H), λ.26 (d, J = 2.7 Hz, 1H), 8.78 (s, 1H), 8.54 (d, J = 2.7 Hz, 1H), 8.18 (d, J = 9.4 Hz, 1H), 7.42 (d, J = 9.1 Hz, 1H), 4.16 (d, J = 3.0 Hz, 3H), 3.72 (d, J = 10.4 Hz, 2H), 3.65 (s, 2H), 2.49 (s, 1H), 2.12 (s, 1H), 1.81 (s, 1H). LCMS (ES, m/z): 380 [M+H] + ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.34 (s, 1H), λ.28 (s, 1H), 8.7λ (d, J = 1.1 Hz, 1H), 8.54 (d, J = 2.7 Hz, 1H), 8.21 (d, J = 9.3 Hz, 1H), 7.44 (d, J = 9.4 Hz, 1H), 4.16 (s, 3H), 3.75 (s, 4H), 3.69 – 3.56 (m, 1H), 2.18 (s, 1H), 1.91 (s, 1H). Example 145: Synthesis of Compound 383 Synthesis of Intermediate C103 To a stirred solution of 2,6-dichloro-1,5-naphthyridine (500 mg, 2.512 mmol, 1 equiv) and tert- butyl 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6 -dihydro-2H-pyridine-1- carboxylate (1.05 g, 3.266 mmol, 1.3 equiv) in dioxane (16 mL) and H ₂ O (4 mL) were added Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (205 mg, 0.251 mmol, 0.1 equiv) and K ₂ CO ₃ (1.04 g, 7.536 mmol, 3 equiv) in portions at room temperature. The resulting mixture was stirred for additional 3 hr at 80 °C. The mixture was allowed to cool down to room temperature. The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The combined organic layers were washed with water (3 x 30 mL), dried over anhydrous Na ₂ SO ₄ . 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 tert-butyl 4-(6-chloro-1,5-naphthyridin-2-yl)-2-methyl-5,6-dihydro -2H-pyridine- 1-carboxylate (500 mg, 55%) as a solid. LCMS (ES, m/z): 360 [M+H] To a stirred solution of tert-butyl 4-(6-chloro-1,5-naphthyridin-2-yl)-2-methyl -5,6-dihydro-2H- pyridine-1-carboxylate (450 mg, 1.251 mmol, 1 equiv) and 7-fluoro-6-(methoxymethoxy)-2- methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazo le (630 mg, 1.876 mmol, 1.5 equiv) in 1,4-dioxane (16 mL) and H ₂ O (4 mL) were added Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (102 mg, 0.125 mmol, 0.1 equiv) and K3PO4 (796 mg, 3.753 mmol, 3 equiv) in portions at room temperature. The resulting mixture was stirred for additional 4 hr at 90°C. The mixture was allowed to cool down to room temperature. The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The combined organic layers were washed with water (3 x 30 mL), dried over anhydrous Na ₂ SO ₄ . 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 tert-butyl 4-{6- [7-fluoro-6-(methoxymethoxy)-2-methylindazol-5-yl] -1,5-naphthyridin-2-yl} -2-methyl-5,6- dihydro-2H-pyridine-1-carboxylate (290 mg, 43%) as a solid. LCMS (ES, m/z): 534 [M+H] Synthesis of Intermediate C105 A solution of tert-butyl 4-{6-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5-yl]-1,5- naphthyridin-2-yl}-2-methyl-5,6-dihydro-2H-pyridine-1-carbox ylate (260 mg, 0.487 mmol, 1.00 equiv) and Pd/C (518 mg, 4.870 mmol, 10 equiv) in methanol (30 mL) was stirred for 8 hr at room temperature under H ₂ atmosphere. The resulting mixture was filtered, the filter cake was washed with methanol (3 x 10mL). The filtrate was concentrated under reduced pressure. The resulting mixture and MnO ₂ (424 mg, 4.870 mmol, 10 equiv) in dichloroethane (30 mL) was stirred for 2 hr at 80 °C. The resulting mixture was filtered, the filter cake was washed with CH ₂ Cl ₂ (3 x 10 mL). The filtrate was concentrated under reduced pressure. This resulted in tert- butyl 4-{6-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5-yl]-1,5- naphthyridin-2-yl}-2- methylpiperidine-1-carboxylate (280 mg, 96%) as a solid. LCMS (ES, m/z): 536 [M+H] Synthesis of Intermediate C106 To a stirred solution of tert-butyl 4-{6-[7-fluoro-6-(methoxymethoxy)-2-methylindazol -5- yl]-1,5-naphthyridin-2-yl}-2-methylpiperidine-1-carboxylate (250 mg, 0.467 mmol, 1 equiv) in MeOH (10 mL) was added HCl(gas)in 1,4-dioxane (5 mL) dropwise at room temperature. The resulting mixture was stirred for additional 3 hr at room temperature. The resulting mixture was concentrated under vacuum. This resulted in 7-fluoro-2-methyl-5-[6-(2-methylpiperidin-4-yl)- 1,5-naphthyridin-2-yl]indazol-6-ol (150 mg) as a solid. LCMS (ES, m/z): 392 [M+H] The crude product (7-fluoro-2-methyl-5-[6-(2-methylpiperidin-4-yl)-1,5-naphthy ridin-2- yl]indazol-6-ol (150 mg, 0.766 mmol, 1 equiv) ) was purified by Chiral Prep-HPLC (Condition 4, Gradient 3) to afford 7-fluoro-2-methyl-5-{6-[(2R,4R)-2-methylpiperidin-4-yl]-1,5- naphthyridin-2-yl}indazol-6-ol (22.6 mg, 7.53%) and 7-fluoro-2-methyl-5-{6-[(2S,4R)-2- methylpiperidin-4-yl]-1,5-naphthyridin-2-yl}indazol-6-ol (7.3 mg, 2%) as a solid. Analysis data Example 146: Synthesis of Compound 298 Synthesis of Intermediate C107 Into a 25 mL vial were added N-tert-butyl-1-[6-(trimethylstannyl)-1,5-naphthyridin-2-yl] pyrrolidin-3-amine (100 mg, 0.231 mmol, 1 equiv), 5-bromo-6-methoxy-2-methylpyrazolo[4,3- b]pyridine (55.88 mg, 0.231 mmol, 1 equiv), dioxane (10 mL) and Pd(DtBPF)Cl ₂ (15.05 mg, 0.023 mmol, 0.1 equiv) at room temperature. The resulting mixture was stirred for 3 hr at 100 °C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. The reaction was quenched by the addition of water/KF (20 mL) at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with brine (1 x 20 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by Prep-TLC (CH ₂ Cl ₂ /MeOH 10:1) to afford N-tert-butyl-1-(6-{6-methoxy-2-methylpyrazolo[4,3-b]pyridin- 5-yl}-1,5- naphthyridin-2-yl) pyrrolidin-3-amine (50 mg, 50%) as a solid. LCMS (ES, m/z):432 [M+H] ⁺ Synthesis of Compound 298 Into a 25mL vial were added N-tert-butyl-1-(6-{6-methoxy-2-methylpyrazolo[4,3-b]pyridin- 5- yl} -1,5-naphthyridin-2-yl)pyrrolidin-3-amine (50 mg, 0.116 mmol, 1 equiv), DCE (5 mL) and BBr3 (1 mL) at room temperature. The resulting mixture was stirred for overnight at 50 °C. The reaction was quenched by the addition of methanol (5 mL) at 0 °C. The resulting mixture was concentrated under reduced pressure. The mixture was basified to pH 8 with saturated NaHCO ₃ (aq.). The aqueous layer was extracted with CH ₂ Cl ₂ (3x10 mL). The combined organic layers were washed with brine (1 x 15 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The crude product (45 mg) was purified by Prep- HPLC (Condition 1, Gradient 28) to afford 5-{6-[3-(tert-butylamino)pyrrolidin-1-yl]-1,5- naphthyridin-2-yl} -2-methylpyrazolo[4,3-b]pyridin-6-ol (9.9 mg, 20%) as a solid. LCMS (ES, m/z):418 [M+H] ^{+ 1} H NMR (400 MHz, DMSO-d6) δ 14.20 (s, 1H), 8.75 (d, J = 9.0 Hz, 1H), 8.66 (s, 1H), 8.22 – 8.10 (m, 2H), 7.35 (d, J = 1.0 Hz, 1H), 7.19 (d, J = 9.3 Hz, 1H), 4.18 (s, 3H), 3.88 (s, 1H), 3.73 (s, 1H), 3.59 – 3.45 (m, 2H), 3.23 – 3.09 (m, 1H), 2.19 (s, 1H), 1.76 (s, 2H), 1.10 (s, 9H). Example 147: Synthesis of Compounds 347 and 349 Synthesis of Intermediate C108 Into a 250 mL 3-necked round-bottom flask was added to 5-bromo-7-fluoro-6-methoxy-2- methyl-2H-indazole (5 g, 19.37 mmol, 2.20 equiv) and DCE (50.0 mL). Then BBr3 (60 mL, 3 equiv, 1 M in dioxane) was added dropwise to the mixture at 0°C in 10 min. And the temperature was warmly to room temperature and the resulting solution was stirred for 1 h at room temperature. The reaction was then quenched by the addition of 100 mL of methanol at 0 °C and the solvent were removed in vacuo. The pH value of the solution was adjusted to7 with saturated NaHCO ₃ . The resulting solution was extracted with 3 x 100 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated. This resulted in 4.3 g (crude) of 5-bromo-7-fluoro-2-methyl-2H-indazol-6-ol as a solid which was used directly in the subsequent step. Synthesis of Intermediate C109 Into a 40mL vial purged and maintained with an inert atmosphere of nitrogen, was placed 5- bromo-7-fluoro-2-methyl-2H-indazol-6-ol (235 mg, 0.96 mmol, 1.00 equiv), tert-butyl ((1r,3r)-3- fluorocyclobutyl)(1-(6-(trimethylstannyl)-1,5-naphthyridin-2 -yl)pyrrolidin-3-yl)carbamate (528 mg, 0.960 mmol, 1.00 equiv), Pd(dtbpf)Cl ₂ (62 mg, 0.0960 mmol, 0.1 equiv) and 1,4-dioxane (20 mL). The resulting solution was stirred for 2 hr at 100 °C. After that the reaction was colder at room temperature and was extracted with 3 x 20 mL of ethyl acetate. The organic layers combined and dried over anhydrous sodium sulfate and concentrated. The residue was applied onto a silica gel column with ethyl acetate/hexane (1:1). This resulted in 100.0 mg as a solid that was used in the following step without further purification. LCMS (ES, m/z): 551 [M+H] ⁺ Synthesis of Intermediate C110 Into a 40-mL round-bottom was placed tert-butyl (1-(6-(7-fluoro-6-hydroxy-2-methyl-2H- indazol-5-yl) -1,5-naphthyridin-2-yl)pyrrolidin-3-yl)((1r,3r)-3-fluorocycl obutyl)carbamate (100 mg, 0.182 mmol, 1.00 equiv), MeOH (1 mL), HCl (g) in dioxane (3.00mL, 1 mol/L, 3 equiv. ). The resulting solution was stirred for 1 h at room temperature. The resulting mixture was concentrated. The crude product was purified by prep-HPLC (Condition 3, Gradient 22) to afford 7-fluoro-5-(6-(3-(((1r,3r)-3-fluorocyclobutyl) amino)pyrrolidin-1-yl)-1,5-naphthyridin-2-yl)-2- methyl-2H-indazol-6-ol (50 mg, 63%) as a solid . LCMS (ES, m/z): 451 [M+H] + Synthesis of Compounds 347 and 349

7-fluoro-5-(6-(3-(((1r,3r)-3-fluorocyclobutyl)amino)pyrrolid in-1-yl)-1,5-naphthyridin-2-yl)-2- methyl-2H-indazol-6-ol (52 mg) was purified by Chiral prep-HPLC (Condition 4, Gradient 6) to afford 7-fluoro-5-(6-((R)-3-(((1r,3R)-3-fluorocyclobutyl)amino)pyrr olidin-1-yl)-1,5- naphthyridin-2-yl)-2-methyl-2H-indazol-6-ol (9.9 mg, 14 %) and 7-fluoro-5-(6-((R)-3-(((1r,3R)- 3-fluorocyclobutyl)amino)pyrrolidin-1-yl)-1,5-naphthyridin-2 -yl)-2-methyl-2H-indazol-6-ol (10.7 mg, 14%). LCMS (ES, m/z): 451 [M+H] ⁺ Compound 348: ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 14.40 (s, 1H), 8.48 (d, J = 2.7 Hz, 1H), 8.44 – 8.38 (m, 2H), 8.16 (d, J = 9.3 Hz, 1H), 8.09 (dd, J = 9.1, 0.8 Hz, 1H), 7.19 (d, J = 9.3 Hz, 1H), 5.21 (ddd, J = 59.9, 6.3, 3.0 Hz, 1H), 4.16 (s, 3H), 3.73 (d, J = 25.1 Hz, 2H), 3.65 – 3.52 (m, 2H), 3.19 – 2.73 (m, 1H), 2.47 – 2.31 (m, 2H), 2.30 – 2.09 (m, 3H), 1.97 – 1.83 (m, 1H). Compound 347: ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.40 (s, 1H), 8.48 (d, J = 2.6 Hz, 1H), 8.44 – 8.38 (m, 2H), 8.15 (d, J = 9.3 Hz, 1H), 8.09 (dd, J = 9.1, 0.8 Hz, 1H), 7.18 (d, J = 9.3 Hz, 1H), 5.35 – 5.05 (m, 1H), 4.16 (s, 3H), 3.76 (dd, J = 10.2, 5.6 Hz, 2H), 3.73 – 3.57 (m, 2H), 3.56 – 3.51 (m, 1H), 2.97 – 2.88 (m, 1H), 2.46 – 2.35 (m, 2H), 2.30 – 2.10 (m, 3H), 1.97 – 1.81 (m, 1H). Example 148: Synthesis of Compound 374 Synthesis of Intermediate C111

To a solution of tert-butyl N-[1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3-yl]-N-[(1r ,3r) -3- fluorocyclobutyl]carbamate (70 mg, 0.166 mmol, 1 equiv) and 4-fluoro-5-(methoxymethoxy)-2- methyl-6- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol e (112.14 mg, 0.332 mmol, 2 equiv) in 1,4-dioxane (1 mL)and H ₂ O (0.25 mL) were added K ₂ CO ₃ (68.95 mg, 0.498 mmol, 3 equiv) and Pd(dppf)Cl ₂ (12.17 mg, 0.017 mmol, 0.1 equiv). After stirring for 5 hr at 80 °C under a nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure. The residue was purified by Prep-TLC/silica gel column chromatography, eluted with CH ₂ Cl ₂ /MeOH (9:1) to afford tert-butyl N-(1-{6-[4-fluoro-5-(methoxymethoxy) -2-methyl-1,3- benzoxazol-6-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl)-N-[( 1r,3r)-3- fluorocyclobutyl]carbamate (30 mg, 30%) as a solid. Synthesis of Compound 374 To a solution of tert-butyl N-(1-{6-[4-fluoro-5-(methoxymethoxy)-2-methyl-1,3-benzoxazol -6- yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl)-N-[(1r,3r)-3-fluo rocyclobutyl]carbamate (30 mg, 0.050 mmol, 1 equiv) in DCM (1 mL) was added TFA (0.2 mL). After stirring for 1 hr at room temperature under a nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Condition 1, Gradient 25) to afford 4-fluoro-2-methyl-6-[6-(3-{[(1r,3r)-3-fluorocyclobutyl] amino}pyrrolidin-1-yl) -1,5-naphthyridin-2-yl]-1,3-benzoxazol-5-ol (1.6 mg, 7%) as a solid. LCMS (ES, m/z): 452 [M+H] + ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 15.06 (s, 1H), 8.45 (d, J = 9.2 Hz, 1H), 8.33 (d, J = 1.4 Hz, 1H), 8.14 (dd, J = 22.9, 9.2 Hz, 2H), 7.19 (d, J = 9.3 Hz, 1H), 5.19 (dtt, J = 56.9, 6.5, 3.6 Hz, 1H), 3.72 (s, 2H), 3.55 (s, 2H), 3.34 – 3.37(m, 1H) 2.64 (s, 3H), 2.34 – 2.43(m, 3H), 2.14 – 2.29 (m, 3H), 1.87 (d, J = 31.1 Hz, 1H). Example 149: Synthesis of Compounds 397, 398, and 399 Synthesis of Intermediate C112 To a stirred solution of 5-{6-chloropyrido[3,2-d]pyrimidin-2-yl}-6-methoxy-2,7- dimethylindazole (200 mg, 0.589 mmol, 1 equiv) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-2,5-dihydropyrrole-1-carboxylate (174 mg, 0.589 mmol, 1 equiv) in dioxane (5 mL) and H ₂ O (1 mL) were added K ₂ CO ₃ (203 mg, 1.472 mmol, 2.5 equiv) and Pd(dppf)Cl ₂ (43 mg, 0.059 mmol, 0.1 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 hr at 80°C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. The reaction was quenched by the addition of water (20 mL) at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 5 mL). The combined organic layers were washed with brine (1 x 10 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reverse flash chromatography (Condition 7, Gradient 4) to afford tert-butyl 3-[2-(6- methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2-d]pyrimidin-6-yl ]-4,5-dihydropyrrole-1- ^{carboxylate (187 mg, 67%) as a solid. LCMS (ES, m/z): 473 [M+H] +} Synthesis of Intermediate C113

To a solution of tert-butyl 3-[2-(6-methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2-d]pyrimi din-6- yl]-4,5-dihydropyrrole-1-carboxylate (187 mg, 0.396 mmol, 1 equiv) in ethyl acetate (5 mL) was added Pd/C (42 mg, 0.396 mmol, 1 equiv) under nitrogen atmosphere. The mixture was hydrogenated at room temperature for 5 hr under hydrogen atmosphere using a hydrogen balloon, filtered through a Celite pad and concentrated under reduced pressure. The residue was dissolve in DCE (5 mL) and added MnO ₂ (301 mg, 3.460 mmol, 10 equiv) in portions at room temperature. The resulting mixture was stirred for 4 hr at 60 °C. The mixture was allowed to cool down to room temperature. The resulting mixture was filtered. the filter cake was washed with CH ₂ Cl ₂ (3 x 5 mL). The filtrate was concentrated under reduced pressure to afford tert-butyl 3- [2-(6-methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2-d]pyrimidi n-6-yl]pyrrolidine-1-carboxylate (135 mg, 82%) as a solid. LCMS (ES, m/z): 475 [M+H] ⁺ Synthesis of Compound 397 To a stirred solution of tert-butyl 3-[2-(6-methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2- d]pyrimidin-6-yl]pyrrolidine-1-carboxylate (130 mg, 0.274 mmol, 1 equiv) in DCE (5 mL) was added BBr ₃ (343 mg, 1.370 mmol, 5 equiv) dropwise at room temperature. The resulting mixture was stirred for 0.5 hr at 80°C. The mixture was allowed to cool down to room temperature. The reaction was quenched by the addition of water (5 mL) at room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by reverse flash (Condition 4, Gradient 2) to afford 2,7-dimethyl-5-[6-(pyrrolidin-3-yl)pyrido[3,2-d]pyrimidin-2- yl]indazol-6- ol; trifluoroacetic acid (20 mg, 15%) as a solid. LCMS (ES, m/z): 361 [M+H] ^{+ 1} H NMR (300 MHz, Methanol-d ₄ ) δ λ.65 (d, J = 0.8 Hz, 1H), 9.11 (d, J = 0.7 Hz, 1H), 8.48-8.31 (m, 2H), 7.98 (d, J = 8.8 Hz, 1H), 4.31-4.18 (m, 1H), 4.24 (s, 3H), 4.10 (ddd, J = 13.2, 7.5, 5.8 Hz, 1H), 3.97 (dd, J = 11.8, 5.7 Hz, 1H), 3.74 (dd, J = 11.7, 7.4 Hz, 1H), 3.66-3.45 (m, 2H), 2.75-2.56 (m, 1H), 2.60-2.37 (m, 3H), 2.34 (dt, J = 13.4, 6.9 Hz, 1H). 2,7-dimethyl-5-[6-(pyrrolidin-3-yl)pyrido[3,2-d]pyrimidin-2- yl]indazol-6-ol; trifluoroacetic acid was separated Chiral-Prep-HPLC (Condition 7, Gradient 1) to afford (R)-2,7-dimethyl-5-(6- (pyrrolidin-3-yl)pyrido[3,2-d]pyrimidin-2-yl)-2H-indazol-6-o l (7.3 mg, 43%) as a solid and (S)- 2-ethyl-4-(3-(ethylamino)pyrrolidin-1-yl)-N-(8-fluoro-2-meth ylimidazo[1,2-a]pyridin-6-yl)-2H- indazole-7-carboxamide (3.1 mg, 18%) as a solid. Compound 398：RT = 2.824 min on chiral- HPLC LCMS (ES, m/z): 361 [M+H] ^{+ 1} H NMR (300 MHz, Methanol-d ₄ ) δ λ.58 (s, 1H), 9.02 (s, 1H), 8.36-8.19 (m, 2H), 7.92 (d, J = 8.8 Hz, 1H), 4.19 (s, 3H), 3.81 (q, J = 7.3 Hz, 1H), 3.45 (d, J = 7.2 Hz, 2H), 3.32-3.13 (m, 1H), 2.45 (s, 3H), 2.43 (s, 1H), 2.24 (dq, J = 14.0, 7.1 Hz, 1H). Compound 399：RT = 4.399 min on chiral-HPLC LCMS (ES, m/z): 361 [M+H] ^{+ 1} H NMR (300 MHz, Methanol-d4) δ λ.58 (s, 1H), λ.02 (s, 1H), 8.36-8.19 (m, 2H), 7.92 (d, J = 8.8 Hz, 1H), 4.19 (s, 3H), 3.81 (q, J = 7.3 Hz, 1H), 3.45 (d, J = 7.2 Hz, 2H), 3.32-3.13 (m, 1H), 2.45 (s, 3H), 2.43 (s, 1H), 2.24 (dq, J = 14.0, 7.1 Hz, 1H). Example 150: Synthesis of Compound 455 Synthesis of Intermediate C114 To a stirred solution of 5-bromo-6-methoxy-2-methylindazole-7-carbonitrile (589 mg, 2.212 mmol, 1 equiv) and 4,4,5,5-tetramethyl-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)- 1,3,2- dioxaborolane (674 mg, 2.654 mmol, 1.2 equiv) in dioxane (20 mL) were added KOAc (434 mg, 4.424 mmol, 2 equiv) and Pd(dppf)Cl ₂ (162 mg, 0.221 mmol, 0.1 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 hr at 90°C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. To the above mixture was added 2-bromopyrido[3,2-d]pyrimidin-6-ol (500 mg, 2.212 mmol, 1 equiv), Pd(dppf)Cl ₂ (162 mg, 0.221 mmol, 0.1 equiv), K3PO4 (939 mg, 4.424 mmol, 2 equiv) and H ₂ O (2 mL) in portions at room temperature. The resulting mixture was stirred for additional 3 hr at 90 °C. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ /MeOH (10:1) to afford 5-{6-hydroxypyrido[3,2- d]pyrimidin-2-yl}-6-methoxy-2-methylindazole-7-carbonitrile (110 mg, 15%) as a solid. LCMS (ES, m/z): 333 [M+H] ⁺ Synthesis of Intermediate C115 To a stirred solution of 5-{6-hydroxypyrido[3,2-d]pyrimidin-2-yl}-6-methoxy-2-methyli ndazole- 7-carbonitrile (110 mg, 0.331 mmol, 1 equiv) in MeCN (5 mL) was added POCl ₃ (508 mg, 3.310 mmol, 10 equiv) dropwise at room temperature. The resulting mixture was stirred for 3 h at 80°C. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under vacuum. The residue was dissolved in ethyl acetate (20 mL). The mixture was basified to pH 8 with saturated NaHCO ₃ (aq.). The resulting mixture was extracted with ethyl acetate (3x10 mL). The combined organic layers were washed with brine (1 x 20 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:10) to afford 5-{6-chloropyrido[3,2-d]pyrimidin-2-yl}-6-methoxy-2-methylin dazole-7- carbonitrile (56 mg, 48%) as a solid. LCMS (ES, m/z): 351 [M+H] ⁺ Synthesis of Intermediate C116 To a stirred solution of 5-{6-chloropyrido[3,2-d]pyrimidin-2-yl}-6-methoxy-2-methylin dazole- 7-carbonitrile (55 mg, 0.157 mmol, 1 equiv) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (58 mg, 0.188 mmol, 1.2 equiv) in dioxane (2 mL) and H ₂ O (0.2 mL) were added K ₂ CO ₃ (54 mg, 0.393 mmol, 2.5 equiv) and Pd(dppf)Cl ₂ (12 mg, 0.016 mmol, 0.1 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 90°C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. The reaction was quenched by the addition of water (20 mL) at room temperature. The resulting mixture was extracted with ethyl acetate (3x5 mL). The combined organic layers were washed with brine (3x10 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:10) to afford tert-butyl 4-[2-(7-cyano-6-methoxy-2-methylindazol-5-yl)pyrido[3,2-d]py rimidin-6-yl]-3,6- dihydro-2H-pyridine-1-carboxylate (58 mg, 74%) as a solid. LCMS (ES, m/z): 498 [M+H] ⁺ Synthesis of Intermediate C117 To a solution of tert-butyl 4-[2-(7-cyano-6-methoxy-2-methylindazol-5-yl)pyrido[3,2- d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylate (51 mg, 0.103 mmol, 1 equiv) in MeOH (5 mL) was added Pd/C (55 mg, 0.515 mmol, 5 equiv) under nitrogen atmosphere. The mixture was hydrogenated at room temperature for 5 hr under hydrogen atmosphere using a hydrogen balloon, filtered through a Celite pad and concentrated under reduced pressure. The residue was diluted with DCE (5 mL). To the above mixture was added MnO ₂ (89 mg, 1.030 mmol, 10 equiv) in portions at room temperature. The resulting mixture was stirred for additional 4 h at 60°C. The mixture was allowed to cool down to room temperature. The resulting mixture was filtered; the filter cake was washed with DCE (3 x 10 mL). The filtrate was concentrated under reduced pressure to afford tert-butyl 4-[2-(7-cyano-6-methoxy-2-methylindazol-5- yl)pyrido[3,2-d]pyrimidin-6-yl]piperidine-1-carboxylate (50 mg, 97%) as a solid. LCMS (ES, m/z): 500 [M+H] ⁺ Synthesis of Compound 455 To a stirred solution of tert-butyl 4-[2-(7-cyano-6-methoxy-2-methylindazol-5-yl)pyrido[3,2- d]pyrimidin-6-yl]piperidine-1-carboxylate (60 mg, 0.12 mmol, 1 equiv) in DCE (5 mL) was added BBr ₃ (301 mg, 1.2 mmol, 10 equiv) dropwise at room temperature. The resulting mixture was stirred for 0.5 hr at 80 °C. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by reverse flash chromatography (Condition 4, Gradient 3) to afford 6-hydroxy-2-methyl-5-[6-(piperidin-4- yl)pyrido[3,2-d]pyrimidin-2-yl]indazole-7-carbonitrile; trifluoroacetic acid (13 mg, 21%) as a solid. LCMS (ES, m/z): 386 [M+H] ⁺¹ H NMR (300 MHz, Methanol-d4) δ λ.67 (s, 1H), λ.46 (s, 1H), 8.54-8.42 (m, 2H), 8.02 (d, J = 8.8 Hz, 1H), 4.23 (s, 3H), 3.62 (d, J = 12.9 Hz, 2H), 3.45 (s, 1H), 3.26 (d, J = 12.8 Hz, 2H), 2.43-2.19 (m, 4H). Example 151: Synthesis of Compound 371 Synthesis of Intermediate C118

A solution of 6-{6-chloropyrido[3,2-d]pyrimidin-2-yl}-2-methylimidazo[1,2- a]pyridine-8- carbonitrile (500.0 mg, 1.56 mmol, 1 equiv) ,tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (578.4 mg, 1.87 mmol, 1.2 equiv) ,K ₃ PO ₄ (992.7 mg, 4.67 mmol, 3 equiv) and Pd(dppf)Cl ₂ CH ₂ Cl ₂ (127.0 mg, 0.15 mmol, 0.1 equiv) in dioxane (8 mL) and H ₂ O (2 mL) was stirred for overnight at 80 °C under nitrogen atmosphere. The resulting mixture was diluted with water (20 mL).The resulting mixture was extracted with ethyl acetate (3 x 20 mL). The combined organic layers were washed with brine (1 x 20 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:4) to afford tert-butyl 4-(2-{8-cyano-2-methylimidazo[1,2-a]pyridin-6-yl}pyrido[3,2- d]pyrimidin-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (120.0 mg, 16%) as a solid. LCMS (ES, m/z): 468 [M+H] ⁺ Synthesis of Intermediate C119 To a solution of tert-butyl 4-(2-{8-cyano-2-methylimidazo[1,2-a]pyridin-6-yl}pyrido[3,2- d]pyrimidin-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (40.0 mg, 0.09 mmol, 1 equiv) in THF (16 mL) was added Pd/C (91.0 mg, 0.86 mmol, 10 equiv) under nitrogen atmosphere in a 50 mL round-bottom flask. The mixture was hydrogenated at room temperature for 30 min under hydrogen atmosphere using a hydrogen balloon, filtered through a Celite pad and concentrated under reduced pressure. The residue was purified by Prep-TLC (PE/EA 1:1) to afford tert-butyl 4-(2-{8-cyano-2-methylimidazo[1,2-a]pyridin-6-yl}pyrido[3,2- d]pyrimidin-6-yl)piperidine-1- carboxylate (17.0 mg, 42%) as a solid. LCMS (ES, m/z): 470 [M+H] ⁺ Synthesis of compound 371 A solution of tert-butyl 4-(2-{8-cyano-2-methylimidazo[1,2-a]pyridin-6-yl}pyrido[3,2- d]pyrimidin-6-yl)piperidine-1-carboxylate (17.0 mg, 0.03 mmol, 1 equiv) in DCM (2 mL) and TFA (0.5 mL) was stirred for 1h at room temperature. The resulting mixture was concentrated under vacuum. The crude product (30 mg) was purified by Prep-HPLC (Condition 11, Gradient 1)to afford 2-methyl-6-[6-(piperidin-4-yl)pyrido[3,2-d]pyrimidin-2-yl]im idazo[1,2-a]pyridine-8- carbonitrile (0.9 mg, 7%) as a solid. LCMS (ES, m/z): 370 [M+H] ^{+ 1} H NMR (400 MHz, DMSO-d6) δ λ.8λ (d, J = 1.6 Hz, 1H), 9.67 (s, 1H), 8.79 (d, J = 1.6 Hz, 1H), 8.44 (d, J = 8.9 Hz, 1H), 8.10 (s, 1H), 8.03 (d, J = 8.9 Hz, 1H), 3.18 – 3.03 (m, 3H), 2.70 (p, J = 1.8 Hz, 1H), 2.65 (d, J = 11.3 Hz, 1H), 2.44 (s, 3H), 1.91 (d, J = 12.4 Hz, 2H), 1.84 – 1.69 (m, 2H), . Example 152: Synthesis of Compounds 366 and 456 Synthesis of Intermediate C120 Into a 250 mL round-bottom flask were added tert-butyl 4-oxopiperidine-1-carboxylate (8 g, 40.151 mmol, 1 equiv), DMF-DMA (1.39 g, 60.227 mmol, 1.5 equiv) and DMF (80 mL). The mixture was stirred for 1.2 hr at 110 °C, the reaction was quenched by the addition of water (100 mL) at room temperature. The aqueous layer was extracted with ethyl acetate (20 ml x 3). The organic layers were washed with brine (20 ml), dried over anhydrous Na ₂ SO4. After filtration, the filtrate was concentrated under reduced pressure. This resulted in tert-butyl (3E)-3- [(dimethylamino)methylidene]-4-oxopiperidine -1-carboxylate (10 g, 97%) as an oil. Synthesis of Intermediate C121 Into a 250 mL sealed tube were added tert-butyl (3E)-3-[(dimethylamino)methylidene] -4- oxopiperidine-1-carboxylate (9 g, 35.387 mmol, 1 equiv), hydrazine hydrate (1.97 g, 39.319 mmol, 1 equiv) and EtOH (100 mL), the mixture was stirred for 6 hr at 80 °C. Then the reaction was quenched by the addition of water (100 mL). The resulting mixture was concentrated under reduced pressure and the aqueous layer was extracted with ethyl acetate (3 x 25 mL). The combined organic layers were concentrated under reduced pressure. The residue was purified by reverse flash chromatography (Condition 3, Gradient 3) to afford tert-butyl 2H,4H,6H,7H- pyrazolo[4,3-c]pyridine-5-carboxylate (8 g, 91%) as a solid. Synthesis of Intermediate C123 A solution of tert-butyl 2H,4H,6H,7H-pyrazolo[4,3-c]pyridine-5-carboxylate (8 g, 35.830 mmol, 1 equiv) in THF (80 mL) was treated with NaH (1.03 g, 42.996 mmol, 1.2 equiv) for 10 min at 0 °C under nitrogen atmosphere, then added MeI (6.10 g, 42.996 mmol, 1.2 equiv) at room temperature and the mixture was stirred for 12 hr at room temperature. The reaction was quenched by the addition of water (100 mL) at 0°C. The aqueous layer was extracted with ethyl acetate (3x50 mL). The combined organic layers were concentrated under reduced pressure. The crude product was purified by Chiral-Prep-HPLC (Condition 8, Gradient 1) to afford tert-butyl 2-methyl-4H,6H,7H-pyrazolo[4,3-c]pyridine-5-carboxylate (1 g, 12%) as an oil and tert-butyl 1- methyl-4H,6H,7H-pyrazolo[4,3-c]pyridine-5-carboxylate (1.2 g, 14%) as an oil Synthesis of Intermediate C124 A mixture of tert-butyl 2-methyl-4H,6H,7H-pyrazolo[4,3-c]pyridine-5-carboxylate (1 g, 4.214 mmol, 1 equiv) and HCl(gas)in 1,4-dioxane (10 mL) in MeOH (10 mL) was stirred for 2 hr at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure to afford 2-methyl-4H,5H,6H,7H-pyrazolo[4,3-c]pyridine (450 mg, 77%) as a solid. Synthesis of Intermediate C125 A mixture of tert-butyl 1-methyl-4H,6H,7H-pyrazolo[4,3-c]pyridine-5-carboxylate (1.2 g, 5.057 mmol, 1 equiv)and HCl(gas)in 1,4-dioxane (10 mL) in MeOH (10 mL) was stirred for 2 hr at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure to afford 1-methyl-4H,5H,6H,7H-pyrazolo[4,3-c]pyridine (600 mg, 86%) as a solid. Synthesis of Compounds 366 and 456 A solution of 2-methyl-4H,5H,6H,7H-pyrazolo[4,3-c]pyridine (45.01 mg, 0.328 mmol, 1 equiv) in 1,4-dioxane (3 mL) was treated with N-tert-butyl-1-(6-chloro-1,5-naphthyridin-2- yl)pyrrolidin-3-amine (100 mg, 0.328 mmol, 1.00 equiv), Cs ₂ CO ₃ (213.78 mg, 0.656 mmol, 2 equiv), SPhos Pd Gen.3 (13.47 mg, 0.033 mmol, 0.1 equiv), SPhos (13.47 mg, 0.033 mmol, 0.1 equiv) for 3h at 80°C under nitrogen atmosphere. The resulting mixture was filtered, the filter cake was washed with ethyl acetate (3 x 10 mL). The filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC (Conditio n11, Gradient 2) to afford N- (tert-butyl)-1-(6-(2-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4 ,3-c]pyridin-5-yl)-1,5-naphthyridin- 2-yl)pyrrolidin-3-amine. The product was then purified by Chiral-Prep-HPLC (Condition 4, Gradient 8)to afford (3R)-N-tert-butyl-1-(6-{2-methyl-4H,6H,7H-pyrazolo[4,3-c]pyr idin-5-yl} - 1,5-naphthyridin-2-yl)pyrrolidin-3-amine (1.9 mg, 1%) as a solid and (3S)-N-tert-butyl-1-(6-{2- methyl-4H,6H,7H-pyrazolo[4,3-c]pyridin-5-yl}-1,5-naphthyridi n-2-yl)pyrrolidin-3-amine (1.6 mg, 1%) as a solid . Compound 366: LCMS (ES, m/z): 406[M+H] + ¹ H NMR (400 MHz, DMSO-d6) δ 7.77 – 7.68 (m, 2H), 7.49 (s, 1H), 7.31 (d, J = 9.3 Hz, 1H), 6.88 (d, J = 9.2 Hz, 1H), 4.62 (s, 2H), 3.92 (t, J = 5.9 Hz, 2H), 3.75 (s, 3H), 3.59 (s, 2H), 3.48 (s, 2H), 3.02 (s, 2H), 2.71 (t, J = 5.8 Hz, 2H), 2.14 (s, 1H), 1.70 (d, J = 9.7 Hz, 1H), 1.08 (s, 9H). Compound 456: LCMS (ES, m/z): 406[M+H] + ¹ H NMR- (400 MHz, DMSO-d6) δ 7.73 (dd, J = 9.1, 6.3 Hz, 2H), 7.49 (s, 1H), 7.31 (d, J = 9.4 Hz, 1H), 6.88 (d, J = 9.2 Hz, 1H), 4.62 (s, 2H), 3.92 (t, J = 5.8 Hz, 2H), 3.75 (s, 3H), 3.59 (t, J = 8.2 Hz, 2H), 3.49 (s, 2H), 3.03 (s, 1H), 2.71 (t, J = 5.8 Hz, 1H), 2.14 (s,2H), 1.72 (s, 1H), 1.24 (s, 1H), 1.08 (s, 9H). Example 153: Synthesis of Compounds 401 and 402 Synthesis of Intermediate C126 A mixture of compound N-tert-butyl-1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3- amine (4.7 g, 15.419 mmol, 1 equiv) and Pd(dppf)Cl ₂ (1.13 g, 1.542 mmol, 0.1 equiv) was add to dioxane (400 mL) taken in a round bottom flask. Then, K ₃ PO ₄ (9.82 g, 46.257 mmol, 3 equiv) in H ₂ O (100 mL) was added to mixture. After stirring for 5 min at room temperature, 5- (methoxymethoxy)-2,4-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-d ioxaborolan-2-yl)-1,3- benzoxazole (6.16 g, 18.503 mmol, 1.2 equiv) was added in portions. The resulting mixture was stirred at 100 °C overnight under a nitrogen atmosphere. The mixture was allowed to cool down to room temperature. The resulting mixture was diluted with water (60 mL). The resulting mixture was extracted with ethyl acetate (3 x 60 mL). The combined organic layers were washed with brine (1 x 50 mL), dried over anhydrous Na ₂ SO ₄ . 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 N-tert-butyl-1-{6-[5-(methoxymethoxy)- 2,4-dimethyl-1,3-benzoxazol-6-yl]-1,5-naphthyridin-2-yl}pyrr olidin-3-amine (4.4 g, 56%) as a solid. LCMS (ESI, m/z): 476[M+H] ⁺ . To a solution of N-tert-butyl-1-{6-[5-(methoxymethoxy)-2,4-dimethyl-1,3-benzo xazol-6-yl]-1,5- naphthyridin-2-yl}pyrrolidin-3-amine (2 g, 4.205 mmol, 1 equiv) in DCM (10 mL, 157.306 mmol, 37.41 equiv) were added TFA (5 mL, 67.315 mmol, 16.01 equiv) . After stirring for 4 h at room temperature under a nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure. The crude product was obtained 6-{6-[3-(tert-butylamino)pyrrolidin-1-yl]-1,5- naphthyridin-2-yl}-2,4-dimethyl-1,3-benzoxazol-5-ol (1.6 g, 88%) as a solid. LCMS (ESI, m/z): 432[M+H] ⁺ . 6-{6-[3-(tert-butylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2 -yl}-2,4-dimethyl-1,3-benzoxazol- 5-ol (1.6g, 3.711 mmol, 1 equiv) was purified by chiral-prep-HPLC (Conditio n5, Gradient 1) to afford 6-{6-[(3R)-3-(tert-butylamino)pyrrolidin-1-yl]-1,5-naphthyri din-2-yl}-2,4-dimethyl-1,3- benzoxazol-5-ol (517.2 mg, 27%) and 6-{6-[(3S)-3-(tert-butylamino)pyrrolidin-1-yl]-1,5- naphthyridin-2-yl}-2,4-dimethyl-1,3-benzoxazol-5-ol (480.3 mg, 26%) as a solid. Analysis data Example 154: Synthesis of Compounds 350, 351, and 374-377 Synthesis of Intermediate C128 A solution of tert-butyl N-[1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3-yl]-N-[(1s ,3s)-3- fluorocyclobutyl]carbamate (350 mg, 0.832 mmol, 1 equiv) and 5-(methoxymethoxy)-2-methyl- 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxaz ole (796 mg, 2.496 mmol, 3 equiv), Pd(dppf)Cl ₂ (68mg, 0.083 mmol, 0.1 equiv), K ₂ CO ₃ (345 mg, 2.496 mmol, 3 equiv) in 1,4- dioxane (2.8 mL), water (0.7 mL) was stirred for 2 hr at 80 °C under nitrogen atmosphere. The resulting mixture was extracted with ethyl acetate (1 x 30mL). dried over anhydrous Na ₂ SO4. 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 tert-butyl N-(1-{6-[5- (methoxymethoxy)-2-methyl-1,3-benzoxazol-6-yl]-1,5-naphthyri din-2-yl}pyrrolidin-3-yl)-N- [(1s,3s)-3-fluorocyclobutyl]carbamate (175 mg, 36%) as a solid. Synthesis of Intermediate C129 A solution of tert-butyl N-(1-{6-[5-(methoxymethoxy)-2-methyl-1,3-benzoxazol-6-yl]-1, 5- naphthyridin-2-yl}pyrrolidin-3-yl)-N-[(1s,3s)-3-fluorocyclob utyl]carbamate (173 mg, 0.299 mmol, 1 equiv) in MeOH (1.7 mL), HCl(gas)in 1,4-dioxane (1.7 mL) was stirred for 1h at room temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by trituration with MeOH/DCM =10/1(2.75mL). The resulting mixture was filtered, the filter cake was washed with MeOH (1 x 2 mL). The filtrate was concentrated under reduced pressure. This resulted in 2-methyl-6-[6-(3-{[(1s,3s)-3-fluorocyclobutyl]amino}pyrrolid in-1-yl)- 1,5-naphthyridin-2-yl]-1,3-benzoxazol-5-ol (91 mg, 70%) as a solid. Synthesis of Intermediate C130 The 2-methyl-6-[6-(3-{[(1s,3s)-3-fluorocyclobutyl]amino}pyrrolid in-1-yl)-1,5-naphthyridin-2- yl]-1,3-benzoxazol-5-ol (91 mg) was purified by Chiral-HPLC with the following conditions (Column: CHIRAL ART Cellulose-SB, 2x25 cm, 5 μm; Mobile Phase Aμ MtBE(0.1% DEA)- HPLC, Mobile Phase B: MeOH--HPLC; Flow rate: 20 mL/min; Gradient: 20% B to 20% B in 8.3 min; Wave Length: UV 254/220 nm; RT1(min): 6.09; RT2(min): 7.28; Sample Solvent: MeOH: DCM=1: 1--HPLC; Injection Volume: 0.5 mL; Number Of Runs: 30) to afford (38.4 mg, 37.25%) as a solid and (38.5 mg, 37.73%) as a solid. Analysis data ysis data Example 155: Synthesis of Compound 448 Synthesis of Intermediate C130 Into a 40mL vial were added 2,6-dichloro-1,5-naphthyridine (500 mg, 2.512 mmol, 1 equiv), dioxane (10 mL), K3PO4 (1599.75 mg, 7.536 mmol, 3 equiv) in H ₂ O (2 mL) and Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (204.65 mg, 0.251 mmol, 0.1 equiv) at room temperature. The resulting mixture was stirred for 1h at 90°C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. The reaction was quenched by the addition of Water (30 mL) at room temperature. The resulting mixture was extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine (1x30 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:5) to afford 2-chloro-6-[6-(methoxymethoxy)- 2-methylindazol-5-yl] -1,5-naphthyridine (220 mg, 24.68%) as a light yellow solid. LCMS (ES, m/z):355 [M+H] ⁺ Synthesis of Intermediate C131 Into a 40mL vial were added 2-chloro-6-[6-(methoxymethoxy)-2-methylindazol-5-yl]-1,5- naphthyridine (180 mg, 0.507 mmol, 1 equiv), tert-butyl (7E)-7-[(4- methylbenzenesulfonamido)imino]-4-azaspiro [2.5]octane-4-carboxylate (199.64 mg, 0.507 mmol, 1 equiv), t-BuOLi (121.85 mg, 1.521 mmol, 3 equiv), dioxane (20 mL, 236.079 mmol, 465.33 equiv) and Pd(dppf)Cl ₂ CH ₂ Cl ₂ (41.33 mg, 0.051 mmol, 0.1 equiv) at room temperature. The resulting mixture was stirred overnight at 110 °C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. The reaction was quenched by the addition of water (40 mL) at room temperature. The resulting mixture was extracted with CH ₂ Cl ₂ (3 x 30mL). The combined organic layers were washed with brine (1 x 30 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:4) to afford tert-butyl 7-{6- [6-(methoxymethoxy) -2-methylindazol-5-yl]-1,5-naphthyridin-2-yl}-4-azaspiro[2.5 ]oct-6-ene- 4-carboxylate (70 mg, 26%) as a solid. LCMS (ES, m/z):528 [M+H] ⁺ Into a 25mL round-bottom flask were added tert-butyl 7-{6-[6-(methoxymethoxy)-2- methylindazol -5-yl]-1,5-naphthyridin-2-yl}-4-azaspiro[2.5]oct-6-ene-4-car boxylate (63 mg, 0.119 mmol, 1 equiv), Pd/C (2.54 mg, 0.024 mmol, 0.2 equiv), EA (3 mL) at room temperature. The resulting mixture was stirred for 24 hr at 40 °C under hydrogen atmosphere (1MPa). The resulting mixture was filtered, the filter cake was washed with MeOH (3x3 mL). The filtrate was concentrated under reduced pressure. The crude product was used in the next step directly without further purification. LCMS (ES, m/z):530 [M+H] ⁺ Synthesis of Compound 448 Into a 8mL vial were added tert-butyl 7-{6-[6-(methoxymethoxy)-2-methylindazol-5-yl] -1,5- naphthyridin-2-yl}-4-azaspiro[2.5]octane-4-carboxylate (40 mg, 0.076 mmol, 1 equiv), DCM (2 mL) and TFA (0.2 mL) at room temperature. The resulting mixture was stirred for 1h at room temperature. The mixture was basified to pH 8 with NH ₃ /MeOH. The resulting mixture was concentrated under reduced pressure. The crude product (42 mg) was purified by Prep-(condition 11, Gradient 1) to afford 5-(6-{4-azaspiro[2.5]octan-7-yl}-1,5-naphthyridin-2-yl)-2- methylindazol-6-ol (7.2 mg, 19.82%) as a solid. LCMS (ES, m/z):386 [M+H] ⁺¹ H NMR (400 MHz, DMSO-d6) δ 13.62 (s, 1H), 8.6λ (s, 1H), 8.60 (d, J = 9.2 Hz, 1H), 8.47 (d, J = 9.1 Hz, 1H), 8.41 (d, J = 8.1 Hz, 2H), 7.78 (d, J = 8.7 Hz, 1H), 6.92 (s, 1H), 4.13 (s, 3H), 3.28 – 3.16 (m, 1H), 3.01 (d, J = 12.7 Hz, 1H), 2.79 – 2.68 (m, 1H), 2.18 (t, J = 12.4 Hz, 1H), 2.04 (s, 1H), 1.91 (d, J = 12.8 Hz, 1H), 1.74 (td, J = 12.4, 4.1 Hz, 1H), 1.33 – 1.25 (m, 1H), 0.59 – 0.50 (m, 1H), 0.48 – 0.35 (m, 3H). Example 156: synthesis of compounds 362 and 363 Synthesis of Intermediate C133 Into a 40 mL round-bottom flask were added tert-butyl N-{1-[6-(trimethylstannyl)-1,5- naphthyridin-2-yl] pyrrolidin-3-yl}carbamate (550 mg, 1.153 mmol, 1 equiv), 5-bromo-7-fluoro- 6-(methoxymethoxy) -2-methylindazole (333.21 mg, 1.153 mmol, 1 equiv), Pd(dtbpf)Cl ₂ (75.12 mg, 0.115 mmol, 0.1 equiv) and 1,4-dioxane (10 mL). The mixture solution was stirred for 2 hr at 100 °C. The resulting mixture was concentrated under vacuum. This resulted in tert-butyl N- (1-{6-[7-fluoro-6-(methoxymethoxy) -2-methylindazol-5-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3- yl)carbamate (380 mg, 63%) as a solid. Synthesis of Compounds 362 and 363 A mixture of tert-butyl N-(1-{6-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5-yl]-1 ,5- naphthyridin -2-yl}pyrrolidin-3-yl)carbamate (350 mg, 0.670 mmol, 1 equiv) and HCl(gas) in 1,4-dioxane (3 mL) in methanol (3 mL)was stirred for 2 hr at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The crude product was purified by Chiral-Prep-HPLC (Condition 6, Gradient 2) to afford 5-{6-[(3R)-3- aminopyrrolidin-1-yl]-1,5-naphthyridin-2-yl} -7-fluoro-2-methylindazol-6-ol (5.7 mg, 2%) as a solid and 5-{6-[(3R)-3-aminopyrrolidin-1-yl] -1,5-naphthyridin-2-yl}-7-fluoro-2-methylindazol- 6-ol (4.5 mg, 2%) as a solid. LCMS (ES, m/z): 379 [M+H] + ¹ H NMR (400 MHz, DMSO-d6) δ 14.34 (s, 1H), 8.49 (d, J = 2.6 Hz, 1H), 8.45 (d, J = 9.3 Hz, 1H), 8.43 (d, J = 1.0 Hz, 1H), 8.23 (d, J = 9.3 Hz, 1H), 8.14 (d, J = 9.4 Hz, 3H), 7.25 (d, J = 9.3 Hz, 1H), 4.16 (s, 3H), 4.00 (d, J = 3.7 Hz, 1H), 3.87 (dd, J = 12.1, 6.1 Hz, 1H), 3.83 – 3.62 (m, 3H), 2.40 (dt, J = 13.7, 7.1 Hz, 1H), 2.21 – 2.12 (m, 1H). LCMS (ES, m/z): 379 [M+H] + ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.34 (s, 1H), 8.49 (d, J = 2.7 Hz, 1H), 8.45 (d, J = 9.3 Hz, 1H), 8.43 (d, J = 1.0 Hz, 1H), 8.23 (dd, J = 9.2, 0.8 Hz, 1H), 8.20 – 8.11 (m, 3H), 7.25 (d, J = 9.3 Hz, 1H), 4.16 (s, 3H), 4.03 – 3.97 (m, 1H), 3.87 (dd, J = 12.1, 6.0 Hz, 1H), 3.80 – 3.68 (m, 3H), 2.39 (dd, J = 13.7, 6.4 Hz, 1H), 2.21 – 2.12 (m, 1H). Example 157: Synthesis of Compounds 406 and 407 Synthesis of Intermediate C134

A mixture of compound 6-{6-hydroxypyrido[3,2-d]pyrimidin-2-yl}-2-methylimidazo[1,2 - a]pyridine-8-carbonitrile (40 mg, 0.132 mmol, 1 equiv)and tert-butyl N-methyl-N-[(3S)- pyrrolidin-3-yl]carbamate (31.80 mg, 0.158 mmol, 1.2 equiv) in NMP (7.5 mL, 77.774 mmol, 587.77 equiv)was taken in a 8 ml vial. Then DIEA (34.20 mg, 0.264 mmol, 2 equiv) and BOP (70.23 mg, 0.158 mmol, 1.2 equiv) was added to mixture refluxed with stirring for 4 h at 30 °C. After the reaction was finish, the mixture was allowed to cool down to room temperature. The resulting mixture was diluted with water (10 mL). The resulting mixture was extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with brine (1 x 10 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with DCM/MeOH (1:10) to afford tert-butyl N-[(3S)-1-(2-{8-cyano-2-methylimidazo[1,2-a]pyridin-6-yl}pyr ido[3,2- d]pyrimidin-6-yl)pyrrolidin-3-yl]-N-methylcarbamate (30 mg, 46%). LCMS (ESI, m/z): 485[M+H] ⁺ . To a solution of tert-butyl N-[(3S)-1-(2-{8-cyano-2-methylimidazo[1,2-a]pyridin-6- yl}pyrido[3,2-d]pyrimidin-6-yl)pyrrolidin-3-yl]-N-methylcarb amate (30 mg, 0.062 mmol, 1 equiv) in DCM (4 mL)were added TFA (1 mL) . After stirring for 1 hr at room temperature under a nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC (Condition 12, Gradient 3) to afford 2-methyl-6-{6- [(3S)-3-(methylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyrimidin- 2-yl}imidazo[1,2-a]pyridine-8- carbonitrile (3.2 mg, 13%) as a solid.LCMS (ESI, m/z): 385 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ λ.78 (s, 1H), λ.20 (s, 1H), 8.6λ (s, 1H), 8.0λ (d, J = 9.6 Hz, 2H), 7.41 (d, J = 10.0 Hz, 1H), 3.76 – 3.61 (m, 5H), 2.42 (s, 3H), 2.33 (s, 3H), 2.16 – 2.10 (m, 1H), 1.89 (d, J = 6.5 Hz, 1H). Synthesis of Intermediate C137 Into a 40mL sample bottle were added 6-bromo-2-methylimidazo[1,2-a] pyridine-8-carbonitrile (500 mg, 2.11 mmol, 1 equiv), bis(pinacolato)diboron (699.20 mg, 2.75 mmol, 1.3 equiv), KOAc (623.59 mg, 6.35 mmol, 3 equiv), Pd(dppf)Cl ₂ CH ₂ Cl ₂ (86.27 mg, 0.10 mmol, 0.05 equiv) and dioxane (10 mL). The resulting mixture was stirred for 3 hr at 80 °C under nitrogen atmosphere. The solids were filtered out. The crude product was used in the next step directly without further purification. LCMS: 202[M+H] ⁺ Synthesis of Intermediate C138 Into two 40mL sample bottles were added 2-bromopyrido[3,2-d] pyrimidin-6-ol (400 mg, 1.77 mmol, 1.00 equiv), K3PO4 (1126.91 mg, 5.31 mmol, 3 equiv) in H ₂ O (8 mL) and Pd(dppf)Cl ₂ CH ₂ Cl ₂ (115.33 mg, 0.142 mmol, 0.08 equiv). To the above mixture was dropwise 8- cyano-2-methylimidazo[1,2-a] pyridin-6-ylboronic acid (355.68 mg, 1.77 mmol, 1 equiv) in dioxane (40 mL). The resulting mixture was stirred for overnight at 80 °C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. The reaction was quenched by the addition of water (20 mL). The mixture was filtered out, the filter was concentrated and washed MTBE. After filtration, the precipitated solids were collected. This resulted in 6-{6-hydroxypyrido[3,2-d] pyrimidin-2-yl}-2-methylimidazo[1,2-a] pyridine-8- carbonitrile (200 mg, crude 37%) as a solid. LCMS: 303[M+H] ⁺ Synthesis of Intermediate C139 Into a 40mL sample bottle were added 6-{6-hydroxypyrido[3,2-d] pyrimidin-2-yl}-2- methylimidazo[1,2-a] pyridine-8-carbonitrile (50 mg, 0.16 mmol, 1 equiv), tert-butyl N-methyl- N-[(3R)-pyrrolidin-3-yl] carbamate (39.75 mg, 0.19 mmol, 1.2 equiv), DIEA (64.13 mg, 0.49 mmol, 3 equiv), BOP (87.79 mg, 0.19 mmol, 1.2 equiv) and NMP (15 mL). The resulting mixture was stirred for overnight at 30 °C. The reaction was quenched with Water (30 mL). The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The combined organic layers were washed with NaCl (30 mL) dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-TLC PE/EA (1:1) to afford tert-butyl N-[(3R)-1-(2-{8-cyano-2-methylimidazo[1,2-a] pyridin-6-yl} pyrido[3,2-d] pyrimidin-6-yl) pyrrolidin-3-yl]-N-methylcarbamate (80 mg, 99%) as a solid. LCMS: 485[M+H] ⁺ Synthesis of Compound 407 Into a 50 mL round-bottom flask were added tert-butyl N-[(3R)-1-(2-{8-cyano-2- methylimidazo[1,2-a]pyridin-6-yl}pyrido[3,2-d]pyrimidin-6-yl )pyrrolidin-3-yl]-N- methylcarbamate (50 mg, 0.10 mmol, 1 equiv). TFA (1 mL, 13.46 mmol, 130.47 equiv) and DCM (4 mL). The resulting mixture was stirred for 30 min at room temperature. The mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC (Condition 11, Gradient 2) to afford 2-methyl-6-{6-[(3R)-3-(methylamino)pyrrolidin-1- yl]pyrido[3,2-d]pyrimidin-2-yl}imidazo[1,2-a]pyridine-8-carb onitrile (3.0 mg, 7%) as a solid. LCMS: 385[M+H] ^{+ 1} H NMR (400 MHz, DMSO-d6) δ λ.7λ (d, J = 1.6 Hz, 1H), 9.22 (s, 1H), 8.70 (d, J = 1.6 Hz, 1H), 8.16 – 8.06 (m, 2H), 7.44 (d, J = 9.5 Hz, 1H), 3.76 (s, 1H), 3.65 (s, 2H), 3.55 (s, 1H), 3.45 (s, 1H), 2.67(3H), 2.45 – 2.38 (3H), 2.19 (s, 1H), 1.98 (s, 1H). Example 158: Synthesis of Compound 415 Synthesis of Intermediate C140 To a stirred solution of 2-bromopyrido[3,2-d] pyrimidin-6-ol (250 mg, 1.106 mmol, 1 equiv), Cs ₂ CO ₃ (1081 mg, 3.318 mmol, 3 equiv) and tert-butyl N-isopropyl-N-[(3R)-pyrrolidin-3- yl]carbamate (303 mg, 1.327 mmol, 1.2 equiv) in dioxane (5 mL) was added Pd-PEPPSI-IPentCl 2-methylpyridine (o-picoline) (46 mg, 0.055 mmol, 0.05 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 100°C. The resulting mixture was concentrated under reduced pressure. The residue was purified by reverse flash chromatography to afford tert-butyl N-[(3R)-1-{6-hydroxypyrido[3,2-d] pyrimidin-2-yl} pyrrolidin-3-yl]-N-isopropylcarbamate (150 mg, 36%) as a solid. LCMS (ES, m/z): 374 [M+H] ⁺ Synthesis of Intermediate C141 To a stirred solution of tert-butyl N-cyclopropyl-N-[(3R)-1-{6-hydroxypyrido[3,2-d] pyrimidin- 2-yl}pyrrolidin-3-yl]carbamate (150 mg, 0.404 mmol, 1 equiv) and TEA (122 mg, 1.212 mmol, 3 equiv) in dioxane (10 mL) were added K ₂ CO ₃ (167 mg, 1.212 mmol, 3 equiv) and PyBrOP (282.39 mg, 0.606 mmol, 1.5 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 hr at 100 °C. To the above mixture were added Pd(dppf)Cl ₂ (29 mg, 0.040 mmol, 0.1 equiv), 5-(methoxymethoxy)-2,4-dimethyl-6-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1,3-benzoxazole (269 mg, 0.808 mmol, 2 equiv) and H ₂ O (0.5 mL) at room temperature. The resulting mixture was stirred for additional 2 hr at 100 °C. The mixture was purified by reverse flash chromatography (Condition 10, Gradient 1) to afford tert-butyl N- isopropyl-N-[(3R)-1-{6-[5-(methoxymethoxy)-2,4-dimethyl-1,3- benzoxazol-6-yl]pyrido[3,2- d]pyrimidin-2-yl}pyrrolidin-3-yl]carbamate (300 mg, 39.82%) and tert-butyl N-cyclopropyl-N- [(3R)-1-{6-[5-(methoxymethoxy)-2,4-dimethyl-1,3-benzoxazol-6 -yl]pyrido[3,2-d]pyrimidin-2- yl}pyrrolidin-3-yl]carbamate (120 mg, 53.00%) ) as a solid. LCMS (ES, m/z): 561 [M+H] ⁺ A solution of tert-butyl N-cyclopropyl-N-[(3R)-1-{6-[5-(methoxymethoxy)-2,4-dimethyl- 1,3- benzoxazol-6-yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin-3-yl] carbamate (120 mg, 0.214 mmol, 1 equiv) and trifluoroacetic acid (2 mL) in DCM (10 mL) was stirred for 3 h at room temperature. The resulting mixture was concentrated under vacuum. The reaction was quenched by the addition of NH ₃ (g) in methanol (2 mL) at room temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by reverse flash chromatography (Condition 10, Gradient 1) to afford 6-{2-[(3R)-3-(cyclopropylamino)pyrrolidin-1-yl]pyrido[3,2- d]pyrimidin-6-yl}-2,4-dimethyl-1,3-benzoxazol-5-ol (15 mg, 16%) as a solid. LCMS (ES, m/ : 417 [M+H] ^{+ 1} H NMR (400 MHz, DMSO-d6) δ 14.33 (s, 1H), λ.32 (s, 1H), 8.57 (d, J = λ.3 Hz, 1H), 8.25 (s, 1H), 8.06 (d, J = 9.2 Hz, 1H), 3.77 (s, 2H), 3.62 (s, 2H), 3.50 (s, 2H), 2.62 (s, 3H), 2.56 (s, 3H), 2.40 (s, 2H), 1.9-1.90 (m, 1H), 0.43 (d, J = 6.7 Hz, 2H), 0.27 (s, 2H). Example 159: Synthesis of Compound 433 Synthesis of Intermediate C142 To a stirred solution of 2-bromopyrido[3,2-d]pyrimidin-6-ol (1 g, 4.424 mmol, 1 equiv) and tert- butyl N-cyclopropyl-N-[(3S)-pyrrolidin-3-yl]carbamate (1.2 g, 5.309 mmol, 1.2 equiv) in dioxane (10 mL) were added Cs2CO ₃ (2.9 g, 8.848 mmol, 2 equiv) and Pd-PEPPSI-IPentCl 2- methylpyridine (o-picoline (0.2 g, 0.221 mmol, 0.05 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 1 hr at 80 °C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. The reaction was quenched by the addition of water (20 mL) at room temperature. The resulting mixture was extracted with EtOAc (3x5 mL). The combined organic layers were washed with brine (1x20 mL), dried over anhydrous Na ₂ SO4. 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 tert-butyl N-cyclopropyl-N-[(3S)-1-{6-hydroxypyrido[3,2-d]pyrimidin-2- yl}pyrrolidin-3-yl]carbamate (500 mg, 30%) as a solid. LCMS (ES, m/z): 370 [M-H] - To a stirred solution of tert-butyl N-cyclopropyl-N-[(3S)-1-{6-hydroxypyrido[3,2-d]pyrimidin-2- yl}pyrrolidin-3-yl]carbamate (150 mg, 0.404 mmol, 1 equiv) and PyBrOP (315 mg, 0.606 mmol, 1.5 equiv) in dioxane (10 mL) were added K ₂ CO ₃ (167 mg, 1.212 mmol, 3 equiv) and TEA (123 mg, 1.212 mmol, 3 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 hr at 100°C under nitrogen atmosphere. To the above mixture were added H ₂ O (0.2 mL), 5-(methoxymethoxy)-2,4-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2 - dioxaborolan-2-yl)-1,3-benzoxazole (270 mg, 0.808 mmol, 2 equiv) and Pd(dppf)Cl ₂ (30 mg, 0.040 mmol, 0.1 equiv) in portions at room temperature. The resulting mixture was stirred for additional 4 hr at 100 °C. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:10) to afford tert-butyl N-cyclopropyl-N-[(3S)-1-{6-[5- (methoxymethoxy)-2,4-dimethyl-1,3-benzoxazol-6-yl]pyrido[3,2 -d]pyrimidin-2-yl}pyrrolidin-3- yl]carbamate (100 mg, 44%) as a solid. LCMS (ES, m/z): 561 [M+H] ⁺ A solution of tert-butyl N-cyclopropyl-N-[(3S)-1-{6-[5-(methoxymethoxy)-2,4-dimethyl- 1,3- benzoxazol-6-yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin-3-yl] carbamate (100 mg, 0.178 mmol, 1 equiv) in TFA (2 mL) and DCM (2 mL) was stirred for 2 hr at room temperature. The resulting mixture was concentrated under vacuum. The residue was basified to pH 8 with 7 M NH ₃ (g) in MeOH. The resulting mixture was concentrated under reduced pressure. The residue was purified by reverse flash chromatography (Condition 10, Gradient 2) to afford 6-{2-[(3S)-3- (cyclopropylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyrimidin-6-y l}-2,4-dimethyl-1,3-benzoxazol- 5-ol (35 mg, 47.12%) as a yellow solid. LCMS (ES, m/z): 417 [M+H] ^{+ 1} H NMR (400 MHz, DMSO-d6) δ 14.35 (s, 1H), λ.36 (s, 1H), 8.60 (d, J = 9.3 Hz, 1H), 8.29 (s, 1H), 8.08 (d, J = 9.1 Hz, 1H), 3.79 (s, 1H), 3.65 (s, 3H), 3.51 (s, 2H), 2.63 (s, 3H), 2.41 (s, 3H), 2.12 (s, 3H), 1.93 (s, 1H), 1.24 (s, 1H), 0.42 (d, J = 6.6 Hz, 2H), 0.25 (s, 2H). Example 160: Synthesis of Compound 435 Synthesis of Intermediate C144

To a stirred solution of tert-butyl N-cyclopropyl-N-[(3S)-1-{6-hydroxypyrido[3,2-d]pyrimidin-2- yl}pyrrolidin-3-yl]carbamate (150 mg, 0.404 mmol, 1 equiv) and PyBrOP (283 mg, 0.606 mmol, 1.5 equiv) in dioxane (10 mL) were added K ₂ CO ₃ (168 mg, 1.212 mmol, 3 equiv) and TEA (123 mg, 1.212 mmol, 3 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 hr at 100 °C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. To the above mixture were added H ₂ O (0.2 mL), 5- (methoxymethoxy)-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)-1,3-benzoxazole (258 mg, 0.808 mmol, 2 equiv) and Pd(dppf)Cl ₂ (30 mg, 0.04 mmol, 0.1 equiv) in portions at room temperature. The resulting mixture was stirred for additional 3 hr at 100 °C. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:10) to afford tert-butyl N-cyclopropyl-N-[(3S)-1-{6-[5-(methoxymethoxy)-2-methyl-1,3- benzoxazol-6-yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin-3-yl] carbamate (100 mg, 45%) as a solid. LCMS (ES, m/z): 547 [M+H] ⁺ Synthesis of Compound 435 A solution of tert-butyl N-cyclopropyl-N-[(3S)-1-{6-[5-(methoxymethoxy)-2-methyl-1,3- benzoxazol-6-yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin-3-yl] carbamate (100 mg, 0.183 mmol, 1 equiv) in TFA (2 mL) and DCM (2 mL) was stirred for 2 hr at room temperature. The resulting mixture was concentrated under vacuum. The residue was basified to pH 8 with 7 M NH ₃ (g) in MeOH. The resulting mixture was concentrated under reduced pressure. The residue was purified by reverse flash chromatography (Condition 10, Gradient 4) to afford 6-{2-[(3S)-3- (cyclopropylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyrimidin-6-y l}-2-methyl-1,3-benzoxazol-5-ol (20 mg, 27%) as a solid. LCMS (ES, m/z): 403 [M+H] ^{+ 1} H NMR (400 MHz, DMSO-d6) δ 13.58 (s, 1H), 9.32 (s, 1H), 8.57 (d, J = 9.3 Hz, 1H), 8.40 (s, 1H), 8.07 (d, J = 9.2 Hz, 1H), 7.15 (s, 1H), 3.65 (d, J = 101.0 Hz, 5H), 2.62 (s, 3H), 2.14 (s, 2H), 1.98-1.90 (m, 1H), 0.43 (d, J = 6.8 Hz, 2H), 0.28 (s, 2H). Example 161: Synthesis of Compound 438 Synthesis of Intermediate C145 To a stirred solution of tert-butyl N-cyclopropyl-N-[(3R)-1-{6-hydroxypyrido[3,2-d]pyrimidin-2- yl}pyrrolidin-3-yl]carbamate (150 mg, 0.404 mmol, 1 equiv) and TEA (122 mg, 1.212 mmol, 3 equiv) in dioxane (10 mL) were added K ₂ CO ₃ (167 mg, 1.212 mmol, 3 equiv) and PyBrOP (282.39 mg, 0.606 mmol, 1.5 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 hr at 100 °C. To the above mixture were added Pd(dppf)Cl ₂ (29 mg, 0.040 mmol, 0.1 equiv), 6-(methoxymethoxy)-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2 -dioxaborolan-2- yl)indazole (268.31 mg, 0.808 mmol, 2 equiv) and H ₂ O (0.5 mL) at room temperature. The resulting mixture was stirred for additional 2 hr at 100 °C. The resulting mixture was purified by reverse flash chromatography (Condition 10, Gradient 1) to afford tert-butyl N-cyclopropyl-N- [(3R)-1-{6-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]pyri do[3,2-d]pyrimidin-2- yl}pyrrolidin-3-yl]carbamate (120 mg, 53%) as a solid. LCMS (ES, m/z): 560 [M+H] ⁺ A solution of tert-butyl N-cyclopropyl-N-[(3R)-1-{6-[6-(methoxymethoxy)-2,7-dimethyli ndazol- 5-yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin-3-yl]carbamate (120 mg, 0.214 mmol, 1 equiv) and trifluoroacetic acid (2 mL) in DCM (10 mL) was stirred for 3 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by reverse flash chromatography (Condition 10, Gradient 5) to afford 5-{2-[(3R)-3-(cyclopropylamino)pyrrolidin- 1-yl]pyrido[3,2-d]pyrimidin-6-yl}-2,7-dimethylindazol-6-ol (35 mg, 39%) as a solid. LCMS (ES, m/z): 416 [M+H] ^{+ 1} H NMR (400 MHz, DMSO-d ₆ ) δ 13.65 (s, 1H), λ.30 (s, 1H), 8.56 (d, J = 9.4 Hz, 1H), 8.42 (s, 1H), 8.35 (s, 1H), 8.04 (d, J = 9.2 Hz, 1H), 4.14 (s, 3H), 3.77 (s, 2H), 3.62 (s, 1H), 3.50 (s, 3H), 2.39 (s, 3H), 2.12 (s, 2H), 1.96-1.88 (m, 1H), 0.42 (d, J = 6.8 Hz, 2H), 0.29-0.22 (m, 2H). Example 162: Synthesis of Compound 439 Synthesis of Intermediate C146 To a stirred solution of tert-butyl N-cyclopropyl-N-[(3S)-1-{6-hydroxypyrido[3,2-d]pyrimidin-2- yl}pyrrolidin-3-yl]carbamate (150 mg, 0.404 mmol, 1 equiv) and PyBrOP (315 mg, 0.606 mmol, 1.5 equiv) in dioxane (10 mL) were added K ₂ CO ₃ (168 mg, 1.212 mmol, 3 equiv) and TEA (123 mg, 1.212 mmol, 3 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 hr at 100 °C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. To the above mixture were added 6- (methoxymethoxy)-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-d ioxaborolan-2-yl)indazole (269 mg, 0.808 mmol, 2 equiv), Pd(dppf)Cl ₂ (30 mg, 0.040 mmol, 0.1 equiv) and water (0.2 mL) in portions at room temperature. The resulting mixture was stirred for additional 3 h at 100°C. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:10) to afford tert-butyl N-cyclopropyl-N-[(3S)-1-{6-[6-(methoxymethoxy)-2,7- dimethylindazol-5-yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin- 3-yl]carbamate (100 mg, 44%) as a solid. LCMS (ES, m/z): 560 [M+H] ⁺ A solution of tert-butyl N-cyclopropyl-N-[(3S)-1-{6-[6-(methoxymethoxy)-2,7-dimethyli ndazol- 5-yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin-3-yl]carbamate (80 mg, 0.143 mmol, 1 equiv) in TFA (2 mL) and DCM (2 mL) was stirred for 2 hr at room temperature. The resulting mixture was concentrated under vacuum. The residue was basified to pH 8 with 7 M NH ₃ (g) in MeOH. The resulting mixture was concentrated under reduced pressure. The residue was purified by reverse flash chromatography (Condition 10, Gradient 3) to afford 5-{2-[(3S)-3- (cyclopropylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyrimidin-6-y l}-2,7-dimethylindazol-6-ol (25 mg, 42%) as a solid. LCMS (ES, m/z): 416 [M+H] ⁺¹ H NMR (300 MHz, DMSO-d ₆ ) δ 13.66 (s, 1H), 9.32 (s, 1H), 8.58 (s, 1H), 8.44 (s, 1H), 8.36 (s, 1H), 8.06 (d, J = 8.8 Hz, 1H), 4.14 (s, 3H), 3.75 (s, 1H), 3.68 (s, 2H), 3.50 (s, 2H), 2.39 (s, 3H), 2.12 (s, 2H), 1.93 (s, 1H), 1.74 (s, 1H), 0.46-0.38 (m, 2H), 0.25 (s, 2H). Example 163: Synthesis of Compound 440 Synthesis of Intermediate C147 To a stirred solution of 6-chloro-1,7-naphthyridin-2-ol (150 mg, 0.831 mmol, 1 equiv) and tert- butyl N-cyclopropyl-N-[(3R)-pyrrolidin-3-yl]carbamate (281 mg, 1.246 mmol, 1.5 equiv) in dioxane (5 mL) were added Pd-PEPPSI-IPentCl 2-methylpyridine (o-picoline) (34 mg, 0.042 mmol, 0.05 equiv) and Cs2CO ₃ (811 mg, 2.493 mmol, 3 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 100 C. The resulting mixture was concentrated under reduced pressure. The residue was purified by reverse flash chromatography with the following conditions: column, C ₁₈ silica gel; mobile phase, MeCN in Water (0.1% NH ₃ .H ₂ O+10mmol/L NH ₄ HCO ₃ ), 10% to 50% gradient in 12 min; detector, UV 254 nm to afford tert-butyl N-cyclopropyl-N-[(3R)-1-{6-hydroxypyrido[3,2-d] pyrimidin-2- yl}pyrrolidin-3-yl]carbamate (150 mg, 48%) as a solid.LCMS (ES, m/z): 371 [M+H] ⁺ To a stirred solution of tert-butyl N-cyclopropyl-N-[(3R)-1-(2-hydroxy-1,7-naphthyridin-6- yl)pyrrolidin-3-yl]carbamate (150 mg, 0.405 mmol, 1 equiv) and TEA (122 mg, 1.215 mmol, 3 equiv) in dioxane (10 mL) were added K ₂ CO ₃ (167 mg, 1.215 mmol, 3 equiv) and PyBrOP (377 mg, 0.810 mmol, 2 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 hr at 100 °C. To the above mixture were added Pd(dppf)Cl ₂ (29 mg, 0.041 mmol, 0.1 equiv), 5-(methoxymethoxy)-2,4-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2 -dioxaborolan- 2-yl)-1,3-benzoxazole (269 mg, 0.810 mmol, 2 equiv) and H ₂ O (0.5 mL) at room temperature. The resulting mixture was stirred for additional 2 hr at 100 °C. The resulting mixture was concentrated under reduced pressure. The residue was purified by reverse flash chromatography (Condition 10, Gradient 1) to afford tert-butyl N-cyclopropyl-N-[(3R)-1-{6-[5- (methoxymethoxy)-2,4-dimethyl-1,3-benzoxazol-6-yl]pyrido[3,2 -d]pyrimidin-2-yl}pyrrolidin-3- yl]carbamate (120 mg, 52%) as a solid. LCMS (ES, m/z): 560 [M+H] ⁺ Synthesis of Compound 440 A solution of tert-butyl N-cyclopropyl-N-[(3R)-1-{6-[5-(methoxymethoxy)-2,4-dimethyl- 1,3- benzoxazol-6-yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin-3-yl] carbamate (120 mg, 0.214 mmol, 1 equiv) and trifluoroacetic acid (1 mL) in DCM (5 mL) was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by reverse flash chromatography (Condition 10, Gradient 4) to afford 6-{6-[(3R)-3- (cyclopropylamino)pyrrolidin-1-yl]-1,7-naphthyridin-2-yl}-2, 4-dimethyl-1,3-benzoxazol-5-ol (32 mg, 36%) as a solid. LCMS (ES, m/z): 416 [M+H] ^{+ 1} H NMR (400 MHz, DMSO-d6) δ 14.89 (s, 1H), 9.07 (s, 1H), 8.37 (d, J = 9.3 Hz, 1H), 8.29 – 8.22 (m, 2H), 6.64 (s, 1H), 3.69 (dd, J = 10.4, 6.0 Hz, 1H), 3.52 (ddq, J = 25.3, 17.5, 9.0, 8.1 Hz, 3H), 3.35 (d, J = 5.0 Hz, 1H), 2.62 (s, 3H), 2.41 (s, 3H), 2.23 – 2.06 (m, 2H), 1.93 (dq, J = 13.0, 6.7 Hz, 1H), 0.42 (dd, J = 6.5, 1.7 Hz, 2H), 0.25 (dt, J = 10.2, 6.0 Hz, 2H). Example 164: Synthesis of Compound 441 Synthesis of Intermediate C149 To a stirred solution of 6-chloro-1,7-naphthyridin-2-ol (130 mg, 0.72 mmol, 1 equiv) and tert- butyl N-cyclopropyl-N-[(3S)-pyrrolidin-3-yl]carbamate (245 mg, 1.08 mmol, 1.5 equiv) in dioxane (10 mL) were added Cs2CO ₃ (469 mg, 1.44 mmol, 2 equiv) and Pd-PEPPSI-IPentCl 2- methylpyridine (o-picoline) (5 mg, 0.006 mmol, 0.05 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 hr at 100°C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:10) to afford tert-butyl N-cyclopropyl-N-[(3S)-1-(2-hydroxy-1,7- naphthyridin-6-yl)pyrrolidin-3-yl]carbamate (120 mg, 45%) as a solid. LCMS (ES, m/z): 371 [M+H] ⁺ Synthesis of Intermediate C150 To a stirred solution of tert-butyl N-cyclopropyl-N-[(3S)-1-(2-hydroxy-1,7-naphthyridin-6- yl)pyrrolidin-3-yl]carbamate (120 mg, 0.324 mmol, 1 equiv) and PyBrOP (227 mg, 0.486 mmol, 1.5 equiv) in dioxane (10 mL) were added K ₂ CO ₃ (135 mg, 0.972 mmol, 3 equiv) and TEA (99 mg, 0.972 mmol, 3 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 hr at 100 °C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. To the above mixture was added H ₂ O (0.2 mL), 5- (methoxymethoxy)-2,4-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-d ioxaborolan-2-yl)-1,3- benzoxazole (216 mg, 0.648 mmol, 2 equiv) and Pd(dppf)Cl ₂ (24 mg, 0.032 mmol, 0.1 equiv) in portions at room temperature. The resulting mixture was stirred for additional 3 h at 100°C. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:10) to afford tert-butyl N-cyclopropyl-N-[(3S)-1-{2-[5-(methoxymethoxy)-2,4- dimethyl-1,3-benzoxazol-6-yl]-1,7-naphthyridin-6-yl}pyrrolid in-3-yl]carbamate (90 mg, 50%) as a solid. LCMS (ES, m/z): 560 [M+H] ⁺ A mixture of tert-butyl N-cyclopropyl-N-[(3S)-1-{2-[5-(methoxymethoxy)-2,4-dimethyl- 1,3- benzoxazol-6-yl]-1,7-naphthyridin-6-yl}pyrrolidin-3-yl]carba mate (90 mg, 0.161 mmol, 1 equiv) in DCM (3 mL) and TFA (1 mL) was stirred for 3 hr at room temperature. The resulting mixture was concentrated under reduced pressure. The residue was basified to pH 8 with 7 M NH ₃ (g) in MeOH. The resulting mixture was concentrated under vacuum. The residue was purified by reverse flash chromatography (Condition 10, Gradient 6) to afford 6-{6-[(3S)-3- (cyclopropylamino)pyrrolidin-1-yl]-1,7-naphthyridin-2-yl}-2, 4-dimethyl-1,3-benzoxazol-5-ol (57 mg, 85%) as a solid. LCMS (ES, m/z): 416 [M+H] ^{+ 1} H NMR (300 MHz, DMSO-d6) δ 14.88 (s, 1H), 9.07 (s, 1H), 8.36 (d, J = 8.8 Hz, 1H), 8.24 (d, J = 10.5 Hz, 2H), 6.64 (s, 1H), 3.69 (s, 1H), 3.50 (d, J = 6.7 Hz, 3H), 3.31 (s, 1H), 2.62 (s, 3H), 2.41 (s, 3H), 2.14 (s, 2H), 1.93 (s, 1H), 0.41 (d, J = 6.7 Hz, 2H), 0.25 (s, 2H). Example 165: Synthesis of Compounds 413 and 414 Synthesis of Intermediate C151 To a stirred solution of 2-bromopyrido[3,2-d]pyrimidin-6-ol (250 mg, 1.106 mmol, 1 equiv), Cs2CO ₃ (1081.10 mg, 3.318 mmol, 3 equiv) and (3R)-N-tert-butylpyrrolidin-3-amine (235 mg, 1.659 mmol, 1.5 equiv) in dioxane (5 mL) was added Pd-PEPPSI-IPentCl 2-methylpyridine (o- picoline) (46mg, 0.055 mmol, 0.05 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 100°C. The resulting mixture was concentrated under reduced pressure. The residue was purified by reverse flash chromatography (Condition 10, Gradient 2) to afford 2-[(3R)-3-(tert-butylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyri midin-6-ol) (150 mg, 48%) as a solid. LCMS (ES, m/z): 288 [M+H] ⁺ Synthesis of Intermediate C152

To a stirred solution of 2-[(3R)-3-(tert-butylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyri midin-6-ol (150 mg, 0.522 mmol, 1 equiv) and PyBrOP (365 mg, 0.783 mmol, 1.5 equiv) in dioxane (5 mL) were added TEA (158 mg, 1.566 mmol, 3 equiv) and K ₂ CO ₃ (216mg, 1.566 mmol, 3 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 100°C. The mixture was allowed to cool down to room temperature. To the above mixture was added Pd(dppf)Cl ₂ (38 mg, 0.052 mmol, 0.1 equiv), 5-(methoxymethoxy)-2-methyl-6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazole (199 mg, 0.626 mmol, 1.2 equiv) and H ₂ O (0.5 mL) at room temperature. The resulting mixture was stirred for additional 2 hr at 100 °C. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by reverse flash chromatography (Condition 9, Gradient 2) to afford (3R)-N-tert-butyl-1-{6-[5-(methoxymethoxy)-2-methyl-1,3- benzoxazol-6-yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin-3-ami ne (120 mg, 49%) as a solid. LCMS (ES, m/z): 463 [M+H] ⁺ Synthesis of Compound 413 A solution of (3R)-N-tert-butyl-1-{6-[5-(methoxymethoxy)-2-methyl-1,3-benz oxazol-6- yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin-3-amine (120 mg, 0.267 mmol, 1 equiv) and TFA (0.80 mL) in DCM (3 mL) was stirred for 2 hr at room temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by reverse flash chromatography (Condition 10, Gradient 4) to afford 6-{2-[(3R)-3-(tert-butylamino)pyrrolidin-1-yl]pyrido[3,2- d]pyrimidin-6-yl}-2-methyl-1,3-benzoxazol-5-ol (15 mg, 13%) as a solid. LCMS (ES, m/z): 419 [M+H] ^{+ 1} H NMR (400 MHz, DMSO-d ₆ ) δ 13.54 (s, 1H), λ.36 (s, 1H), 8.59 (d, J = 9.3 Hz, 1H), 8.42 (s, 1H), 8.10 (d, J = 9.3 Hz, 1H), 7.16 (s, 1H), 4.00 (d, J = 20.9 Hz, 1H), 3.80 (s, 2H), 3.58 (s, 2H), 2.63 (s, 3H), 2.27 (s, 1H), 1.90 (s, 1H), 1.18 (s, 9H). Synthesis of Intermediate C153 To a stirred solution of 2-bromopyrido[3,2-d]pyrimidin-6-ol (200 mg, 0.885 mmol, 1 equiv) and (3S)-N-tert-butylpyrrolidin-3-amine (151 mg, 1.062 mmol, 1.2 equiv), Cs2CO ₃ (865 mg, 2.655 mmol, 3 equiv) in dioxane (5 mL) was added Pd-PEPPSI-IPentCl 2-methylpyridine (o-picoline) (38 mg, 0.044 mmol, 0.05 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 100°C. The mixture was allowed to cool down to room temperature. The reaction was quenched by the addition of water (20 mL) at room temperature. The resulting mixture was extracted with ethyl acetate (3x5 mL). The combined organic layers were washed with brine (1x20 mL), dried over anhydrous Na ₂ SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reverse flash chromatography (Condition 9, Gradient 3) to afford 2-[(3S)-3-(tert-butylamino)pyrrolidin-1- yl]pyrido[3,2-d]pyrimidin-6-ol (100 mg, 39%) as a solid. LCMS (ES, m/z): 288 [M+H] ⁺ Synthesis of Intermediate C154 To a stirred solution of 2-[(3S)-3-(tert-butylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyri midin- 6-ol (150 mg, 0.522 mmol, 1 equiv) and TEA (159 mg, 1.566 mmol, 3 equiv) in dioxane (8 mL) were added K ₂ CO ₃ (217 mg, 1.566 mmol, 3 equiv) and PyBrOP (365 mg, 0.783 mmol, 1.5 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for additional 3 h at 100°C. To the above mixture were added 5-(methoxymethoxy)-2- methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-b enzoxazole (333 mg, 1.045 mmol, 2 equiv), Pd(dppf)Cl ₂ (39 mg, 0.052 mmol, 0.1 equiv) and H ₂ O (0.4 mL) in portions at room temperature. The resulting mixture was stirred for additional 2 hr at 100°C. The mixture was allowed to cool down to room temperature. The reaction was quenched by the addition of water (20 mL) at room temperature. The resulting mixture was extracted with ethyl acetate (3x5 mL). The combined organic layers were washed with brine (1 x 20 mL), dried over anhydrous Na ₂ SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reverse flash chromatography (Condition 10, Gradient 7) to afford (3S)-N-tert-butyl- 1-{6-[5-(methoxymethoxy)-2-methyl-1,3-benzoxazol-6-yl]pyrido [3,2-d]pyrimidin-2- yl}pyrrolidin-3-amine (100 mg, 41%) as a solid. LCMS (ES, m/z): 463 [M+H] ⁺ Synthesis of Compound 414 A solution of (3S)-N-tert-butyl-1-{6-[5-(methoxymethoxy)-2-methyl-1,3-benz oxazol-6- yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin-3-amine (100 mg, 0.216 mmol, 1 equiv) in TFA (2 mL) and DCM (2 mL) was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was basified to pH 8 with 7 M NH ₃ (g) in MeOH. The resulting mixture was concentrated under reduced pressure. The residue was purified by reverse flash chromatography(Condition 10, Gradient 2) to afford 6-{2-[(3S)-3-(tert- butylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyrimidin-6-yl}-2-me thyl-1,3-benzoxazol-5-ol (12 mg, 13%) as a solid. LCMS (ES, m/z): 419 [M+H] ^{+ 1} H NMR (400 MHz, DMSO-d ₆ ) δ 13.5λ (s, 1H), 9.31 (s, 1H), 8.56 (d, J = 9.4 Hz, 1H), 8.39 (s, 1H), 8.06 (d, J = 9.2 Hz, 1H), 7.15 (s, 1H), 3.92 (s, 1H), 3.76 (s, 1H), 3.53 (s, 2H), 3.18 (s, 1H), 2.62 (s, 3H), 2.17 (s, 1H), 2.08 (s, 1H), 1.75 (d, J = 11.0 Hz, 1H), 1.10 (s, 9H). Example 166: Synthesis of Compound 415 Synthesis of Intermediate C155 To a stirred solution of 2-bromopyrido[3,2-d] pyrimidin-6-ol (250 mg, 1.106 mmol, 1 equiv), Cs2CO ₃ (1081 mg, 3.318 mmol, 3 equiv) and tert-butyl N-isopropyl-N-[(3R)-pyrrolidin-3- yl]carbamate (303 mg, 1.327 mmol, 1.2 equiv) in dioxane (5 mL) was added Pd-PEPPSI-IPentCl 2-methylpyridine (o-picoline) (46 mg, 0.055 mmol, 0.05 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 hr at 100°C. The resulting mixture was concentrated under reduced pressure. The residue was purified by reverse flash chromatography (Condition 9, Gradient 1) to afford tert-butyl N-[(3R)-1-{6-hydroxypyrido[3,2- d] pyrimidin-2-yl} pyrrolidin-3-yl]-N-isopropylcarbamate (150 mg, 36%) as a solid. LCMS (ES, m/z): 374 [M+H] ⁺ Synthesis of Intermediate C156 To a stirred solution of tert-butyl N-[(3R)-1-{6-hydroxypyrido[3,2-d]pyrimidin-2-yl}pyrrolidin- 3-yl]-N-isopropylcarbamate (500 mg, 1.339 mmol, 1 equiv) and TEA (406 mg, 4.017 mmol, 3 equiv) in dioxane (20 mL) were added K ₂ CO ₃ (555 mg, 4.017 mmol, 3 equiv) and PyBrOP (936 mg, 2.008 mmol, 1.5 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 hr at 100 °C. To the above mixture were added Pd(dppf)Cl ₂ (97 mg, 0.134 mmol, 0.1 equiv), 5-(methoxymethoxy)-2,4-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2 - dioxaborolan-2-yl)-1,3-benzoxazole (892 mg, 2.678 mmol, 2 equiv) and H ₂ O (1 mL) room temperature. The resulting mixture was stirred for 2 hr at 100 °C. The residue was purified by reverse flash chromatography (Condition 10, Gradient5) to afford tert-butyl N-isopropyl-N- [(3R)-1-{6-[5-(methoxymethoxy)-2,4-dimethyl-1,3-benzoxazol-6 -yl] yrido[3,2-d] pyrimidin-2- yl}pyrrolidin-3-yl]carbamate (300 mg, 39%) as a solid. LCMS (ES, m/z): 563 [M+H] ⁺ A solution of tert-butyl N-isopropyl-N-[(3R)-1-{6-[5-(methoxymethoxy)-2,4-dimethyl-1, 3- benzoxazol-6-yl]pyrido 3,2-d]pyrimidin-2-yl}pyrrolidin-3-yl]carbamate (120 mg, 0.213 mmol, 1 equiv) and trifluoroacetic acid (2 mL) in DCM (10 mL) was stirred for 3 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by reverse flash chromatography (Condition 10, Gradient 3) to afford 6-{2-[(3R)-3-(isopropylamino) yrrolidin-1- yl]pyrido 3,2-d]pyrimidin-6-yl}-2,4-dimethyl-1,3-benzoxazol-5-ol (15 mg, 16%) as a solid. LCMS (ES, m/z): 419 [M+H] ^{+ 1} H NMR (400 MHz, DMSO-d ₆ ) δ 14.33 (s, 1H), λ.36 (s, 1H), 8.59 (d, J = 9.4 Hz, 1H), 8.28 (s, 1H), 8.08 (d, J = 9.2 Hz, 1H), 3.86 (s, 1H), 3.77 (s, 1H), 3.60 (s, 2H), 2.94 (s, 1H), 2.62 (s, 3H), 2.41 (s, 3H), 2.19 (s, 2H), 1.86 (s, 1H), 1.06 (d, J = 5.7 Hz, 6H) Example 167: Synthesis of Compound 416 Synthesis of Intermediate C157 To a stirred solution of 2-bromopyrido[3,2-d]pyrimidin-6-ol (250 mg, 1.106 mmol, 1 equiv) and tert-butyl N-isopropyl-N-[(3S)-pyrrolidin-3-yl]carbamate (303 mg, 1.327 mmol, 1.2 equiv) in dioxane (10 mL) were added Pd-PEPPSI-IPentCl 2-methylpyridine (o-picoline) (47 mg, 0.055 mmol, 0.05 equiv) and Cs2CO ₃ (721 mg, 2.212 mmol, 2 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 hr at 100 °C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:10) to afford tert-butyl N-[(3S)-1-{6-hydroxypyrido[3,2- d]pyrimidin-2-yl}pyrrolidin-3-yl]-N-isopropylcarbamate (190 mg, 46%) as a solid. LCMS (ES, m/z): 374 [M-H] ⁺ Synthesis of Intermediate C158 To a stirred solution of tert-butyl N-[(3S)-1-{6-hydroxypyrido[3,2-d]pyrimidin-2-yl}pyrrolidin- 3-yl]-N-isopropylcarbamate (150 mg, 0.402 mmol, 1 equiv) and PyBrOP (314 mg, 0.603 mmol, 1.5 equiv) in dioxane (10 mL) were added TEA (122 mg, 1.206 mmol, 3 equiv) and K ₂ CO ₃ (167 mg, 1.206 mmol, 3 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 hr at 100 °C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. To the above mixture was added 5- (methoxymethoxy)-2,4-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-d ioxaborolan-2-yl)-1,3- benzoxazole (268 mg, 0.804 mmol, 2 equiv), H ₂ O (0.2 mL) and Pd(dppf)Cl ₂ (30 mg, 0.040 mmol, 0.1 equiv) in portions at room temperature. The resulting mixture was stirred for additional 3 hr at 100 °C. The mixture was allowed to cool down to room temperature. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:10) to afford tert-butyl N-isopropyl-N-[(3S)-1-{6-[5- (methoxymethoxy)-2,4-dimethyl-1,3-benzoxazol-6-yl]pyrido[3,2 -d]pyrimidin-2-yl}pyrrolidin-3- yl]carbamate (100 mg, 44%) as a solid. LCMS (ES, m/z): 563 [M+H] ⁺ Synthesis of Compound 416

A solution of tert-butyl N-isopropyl-N-[(3S)-1-{6-[5-(methoxymethoxy)-2,4-dimethyl-1, 3- benzoxazol-6-yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin-3-yl] carbamate (100 mg, 0.178 mmol, 1 equiv) in TFA (2 mL) and DCM (2 mL) was stirred for 2 hr at room temperature. The resulting mixture was concentrated under vacuum. The residue was basified to pH 8 with 7 M NH ₃ (g) in MeOH. The resulting mixture was concentrated under reduced pressure. The residue was purified by reverse flash chromatography (Condition 10, Gradient 3) to afford 6-{2-[(3S)-3- (isopropylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyrimidin-6-yl} -2,4-dimethyl-1,3-benzoxazol-5-ol (35 mg, 47%) as a solid. LCMS (ES, m/z): 419 [M+H] ^{+ 1} H NMR (300 MHz, DMSO-d6) δ 14.34 (s, 1H), 9.38 (s, 1H), 8.61 (d, J = 8.6 Hz, 1H), 8.30 (s, 1H), 8.10 (s, 1H), 3.86 (s, 3H), 3.62 (s, 2H), 2.96 (s, 1H), 2.63 (s, 3H), 2.41 (s, 3H), 1.90 (s, 1H), 1.24 (s, 1H), 1.12-1.04 (m, 6H). Example 168: Synthesis of Compounds 408-412 Synthesis of Intermediate C159 A solution of 6-bromo-5-methoxy-2-methyl-1,3-benzoxazole (12 g, 49.572 mmol, 1 equiv) and BBr ₃ (62.09 g, 247.860 mmol, 5 equiv) in DCM (100 mL) was stirred for 16 hr at room temperature. The reaction was quenched by the addition of MeOH (5 mL) at 0 °C. The resulting mixture was concentrated under reduced pressure. The mixture was basified to pH 8 with saturated NaHCO ₃ (aq.). The aqueous layer was extracted with DCM (3 x 100 mL). The combined organic layers were washed with brine (1 x 100 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. This resulted in 6-bromo-2- methyl-1,3-benzoxazol-5-ol (8 g, 70%) as a solid. LCMS (ES, m/z): 229 [M+H] ⁺ Synthesis of Intermediate C160 A solution of 6-bromo-2-methyl-1,3-benzoxazol-5-ol (8 g, 35.081 mmol, 1 equiv) and methane, bromomethoxy- (5.26 g, 42.097 mmol, 1.2 equiv) and DIEA (22.67 g, 175.405 mmol, 5 equiv) in DCM (50 mL) was stirred for 2 hr at room temperature. The reaction was quenched with H ₂ O at room temperature. The resulting mixture was extracted with DCM (3 x 50 mL). The combined organic layers were washed with NaCl Solution (1 x 50 mL), dried over anhydrous Na ₂ SO4. After filtration, the filtrate was concentrated under reduced pressure. This resulted in 6-bromo-5- (methoxymethoxy)-2-methyl-1,3-benzoxazole (5 g, 52%) as a solid. LCMS (ES, m/z): 273 [M+H] ⁺ Synthesis of Intermediate C161 A solution of 6-bromo-5-(methoxymethoxy)-2-methyl-1,3-benzoxazole (5 g, 18.376 mmol, 1 equiv) in 1,4-dioxane (20 mL) was treated with potassium acetate (4.51 g, 45.940 mmol, 2.5 equiv) and Pd(dppf)Cl ₂ (1.08 g, 1.470 mmol, 0.08 equiv) for 2 h at 80 °C under nitrogen atmosphere followed by the addition of 4,4,5,5-tetramethyl-2-(tetramethyl-1,3,2-dioxaborolan-2- yl)-1,3,2-dioxaborolane (7.00 g, 27.564 mmol, 1.5 equiv) dropwise portions at 80 °C. The mixture was allowed to cool down to room temperature. The reaction was quenched with H ₂ O at room temperature. The resulting mixture was extracted with EA (3 x 20 mL). The combined organic layers were washed with NaCl Solution (2 x 20 mL), dried over anhydrous Na ₂ SO4. 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 5-(methoxymethoxy)-2- methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-b enzoxazole (3 g, 51%) as a solid. LCMS (ES, m/z): 320 [M+H] ⁺ Synthesis of Intermediate C162 A solution of 2,6-dichloro-1,5-naphthyridine (1.5 g, 7.537 mmol, 1 equiv) in 1,4-dioxane (13 mL) and H ₂ O (4 mL) was treated with K ₂ CO ₃ (3.12 g, 22.611 mmol, 3 equiv) and Pd(dppf)Cl ₂ CH ₂ Cl ₂ (0.61 g, 0.754 mmol, 0.1 equiv) for 2h at 80 °C under nitrogen atmosphere followed by the addition of 5-(methoxymethoxy)-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1,3-benzoxazole (2.41 g, 7.537 mmol, 1 equiv) dropwise portions at 80 °C. The mixture was allowed to cool down to room temperature. The reaction was quenched with H ₂ O at room temperature. The resulting mixture was extracted with EA (3 x 20 mL). The combined organic layers were washed with NaCl Solution (2 x 20 mL), dried over anhydrous Na ₂ SO4. 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-chloro-6-[5- (methoxymethoxy)-2-methyl-1,3-benzoxazol-6-yl]-1,5-naphthyri dine (400 mg, 14%) as a solid. LCMS (ES, m/z): 356 [M+H] ⁺ Synthesis of Intermediate C163 A solutionof 2-chloro-6-[5-(methoxymethoxy)-2-methyl-1,3-benzoxazol-6-yl] -1,5- naphthyridine (80 mg, 0.225 mmol, 1 equiv) and tert-butyl piperazine-1-carboxylate (62.82 mg, 0.338 mmol, 1.5 equiv) and K ₂ CO ₃ (93.23 mg, 0.675 mmol, 3 equiv) in NMP (2 mL) was stirred for 3 hr at 120 ° C. The mixture was allowed to cool down to room temperature. The reaction ^{was quenched with H} 2 ^{O at room temperature. The resulting mixture was extracted with EA (3 x} 10 mL). The combined organic layers were washed with NaCl Solution (2x20 mL), dried over anhydrous Na ₂ SO4. After filtration, the filtrate was concentrated under reduced pressure. This resulted in tert-butyl 4-{6-[5-(methoxymethoxy)-2-methyl-1,3-benzoxazol-6-yl]-1,5- naphthyridin-2-yl}piperazine-1-carboxylate (130 mg, 83%) as a solid. LCMS (ES, m/z): 506 [M+H] ⁺ To a stirred solution of tert-butyl 4-{6-[5-(methoxymethoxy)-2-methyl-1,3-benzoxazol-6-yl]- 1,5-naphthyridin-2-yl}piperazine-1-carboxylate (130 mg, 0.257 mmol, 1 equiv) in DCM (3 mL) was added TFA (1 mL) dropwise at room temperature. The mixture was stirred 1h at room temperature. The reaction liquid was concentrated under reduced pressure. The crude product was purified by reverse phase flash chromatography to afford 2-methyl-6-[6-(piperazin-1-yl)- 1,5-naphthyridin-2-yl]-1,3-benzoxazol-5-ol (11 mg, 12%) as a solid. LCMS (ES, m/z): 362 [M+H] ⁺ Analysis data Example 169: Synthesis of Compound 482 Synthesis of Intermediate C164 A solution of 2-amino-3-methylbenzoic acid (20 g, 132.306 mmol, 1.0 equiv) in acetonitrile (300 mL) was treated with NIS (35.72 g, 158.767 mmol, 1.2 equiv) at room temperature. The resulting mixture was stirred for 2 h at room temperature. A precipitate formed that was collected by filtration and washed with acetonitrile (2 x 50 mL). The resulting solid was dried under infrared light to afford 2-amino-5-iodo-3-methylbenzoic acid (30.2 g, 82%) as a solid. LCMS (ES, m/z): 278 [M+H] ⁺ . Synthesis of Intermediate C165 To a stirred mixture of 2-amino-5-iodo-3-methylbenzoic acid (30 g, 108.279 mmol, 1.0 equiv) and Cs2CO ₃ (70.56 g, 216.558 mmol, 2.0equiv) in DMF (300 mL) was added MeI (19.98 g, 140.763 mmol, 1.3 equiv) at room temperature. The resulting mixture was stirred for 2 h at room temperature, then diluted with water (400 mL) and extracted with ethyl acetate (3 x 400 mL). The organic layers were combined, washed with brine (1 x 300 mL), dried over anhydrous Na ₂ SO4, and filtered. The filtrate was concentrated under reduced pressure to afford methyl 2- amino-5-iodo-3-methylbenzoate (31 g, 98%) as a solid. LCMS (ES, m/z): 292 [M+H] ⁺ . Synthesis of Intermediate C166 To a stirred mixture of methyl 2-amino-5-iodo-3-methylbenzoate (30 g, 103.062 mmol, 1.0 equiv) and TEA (20.86 g, 206.124 mmol, 2.0 equiv) in DCM (300 mL) was added methyl 3- chloro-3-oxopropanoate (15.48 g, 113.368 mmol, 1.1 equiv) dropwise at 0 °C under nitrogen atmosphere. The resulting mixture was stirred for 2 h at 0 °C under nitrogen atmosphere, then quenched with water/ice. The resulting mixture was extracted with CH ₂ Cl ₂ (2 x 200 mL). The organic layers were combined, washed with brine (1x100 mL), dried over anhydrous Na ₂ SO4, and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (2:1) to afford methyl 5- iodo-2-(3-methoxy-3-oxopropanamido)-3-methylbenzoate (16 g, 40%) as a solid. LCMS (ES, m/z): 392 [M+H] ⁺ . Synthesis of Intermediate C167 A solution of methyl 5-iodo-2-(3-methoxy-3-oxopropanamido)-3-methylbenzoate (15 g, 38.347 mmol, 1.0 equiv) in methanol (150 mL) was treated with MeONa (4.14 g, 76.694 mmol, 2.0 equiv) at room temperature. The resulting mixture was stirred for 5 h at 80 °C under nitrogen atmosphere, then cooled to room temperature. A precipitate formed that was collected by filtration and washed with methanol (1 x 20 mL). The resulting solid was dried under infrared light to afford methyl 6-iodo-8-methyl-2,4-bis(sodiooxy)quinoline-3-carboxylate (13.5 g, 87%) as a solid. LCMS (ES, m/z): 360 [M-2Na+3H] ⁺ . Synthesis of Intermediate C168 A mixture of methyl 6-iodo-8-methyl-2,4-bis(sodiooxy)quinoline-3-carboxylate (13 g, 34.732 mmol, 1.0 equiv) and HCl (6 M) (140 mL) in dioxane (140 mL) was stirred for 3 h at 90 °C, then cooled to room temperature. A precipitate formed that was collected by filtration and washed with water (2 x 50 mL). The resulting solid was dried under infrared light to afford 6-iodo-8- methylquinoline-2,4-diol (8.1 g, 77%) as a solid. LCMS (ES, m/z): 302 [M+H] ⁺ . Synthesis of Intermediate C169 A mixture of 6-iodo-8-methylquinoline-2,4-diol (2 g, 6.643 mmol, 1.0 equiv) and phosphorus oxychloride (10 mL) was stirred for 3 h at 80 °C under nitrogen atmosphere, then cooled to room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (10:1) to afford 2,4-dichloro-6-iodo-8-methylquinoline (1.4 g, 62%) as a solid. LCMS (ES, m/z): 338 [M+H] ⁺ . Synthesis of Intermediate C170 To a stirred mixture of 2,4-dichloro-6-iodo-8-methylquinoline (500 mg, 1.479 mmol, 1.0 equiv) and tert-butyl piperazine-1-carboxylate (330.6 mg, 1.775 mmol, 1.2 equiv) in dioxane (5 mL) was added Cs2CO ₃ (964.0 mg, 2.958 mmol, 2.0 equiv), 1,2,3,4,5-pentaphenyl-1’-(di-tert- butylphosphino)ferrocene (210.3 mg, 0.296 mmol, 0.2 equiv), and Pd2(dba) ₃ (135.5 mg, 0.148 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 6 h at 80 °C under nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to afford tert-butyl 4-(2,4-dichloro-8-methylquinolin-6-yl)piperazine-1-carboxyla te (268 mg, 46%) as a solid. LCMS (ES, m/z): 396 [M+H] ⁺ . Synthesis of Intermediate C171 To a stirred mixture of tert-butyl 4-(2,4-dichloro-8-methylquinolin-6-yl)piperazine-1-carboxyla te (160.0 mg, 0.404 mmol, 1.0 equiv) and 6-(methoxymethoxy)-2,7-dimethyl-5-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)indazole (134.1 mg, 0.404 mmol, 1.0 equiv) in dioxane (2 mL) and water (0.4 mL) was added K ₃ PO ₄ (257.0 mg, 1.212 mmol, 3.0 equiv) and Pd(PPh ₃ ) ₄ (46.6 mg, 0.040 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 80 °C under nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford tert-butyl 4-{4-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol- 5-yl]-8-methylquinolin-6-yl}piperazine-1-carboxylate (210 mg, 92%) as a solid. LCMS (ES, m/z): 566 [M+H] ⁺ . Synthesis of Compound 482 A solution of tert-butyl 4-{4-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]- 8- methylquinolin-6-yl}piperazine-1-carboxylate (100 mg, 0.177 mmol, 1.0 equiv) in DCM (1 mL) was treated with HCl (gas) in 1,4-dioxane (0.25 mL) at room temperature. The resulting mixture was stirred for 2 h at room temperature under nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (SunFire Prep C ₁₈ OBD Column1λ*150 mm, 5μm 10 nm, mobile phase, MeCN in water (0.05% HCl), 35% to 50% gradient in 15 min; detector, UV 254 nm) to afford 5-[4-chloro-8-methyl-6-(piperazin-1- yl)577yrrolidi-2-yl]-2,7-dimethylindazol-6-ol hydrochloride (26.5 mg, 33%) as a solid. LCMS (ES, m/z): 422 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d6) δ 14.60 (s, 1H), λ.46 (s, 2H), 8.58 (d, J = 2.3 Hz, 2H), 8.43 (s, 1H), 7.73 (d, J = 2.6 Hz, 1H), 7.20 (d, J = 2.6 Hz, 1H), 4.17 (s, 3H), 3.63 (t, J = 5.1 Hz, 4H), 3.29 (s, 4H), 2.70 (s, 3H), 2.39 (s, 3H). Example 170: Synthesis of Compound 778 Synthesis of Intermediate C172 To a stirred solution of 2,4,6-trichloroquinazoline (300 mg, 1.285 mmol, 1 equiv) in tetrahydrofuran (3 mL) was added MeONa (231.39 mg, 1.285 mmol, 1.0 equiv, 30%) at room temperature. The resulting mixture was stirred for 2 h at 50 °C, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to afford 2,6-dichloro-4-methoxyquinazoline (240 mg, 82%) as a solid. LCMS (ES, m/z): 229 [M+H] ⁺ . To a stirred mixture of 2,6-dichloro-4-methoxyquinazoline (240 mg, 1.048 mmol, 1 equiv) and 6-(methoxymethoxy)-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2 -dioxaborolan-2-yl)indazole (452.50 mg, 1.362 mmol, 1.3 equiv) in dioxane (3 mL) and water (0.6 mL) was added K ₂ CO ₃ (434.42 mg, 3.144 mmol, 3 equiv) and Pd(dppf)Cl ₂ (76.67 mg, 0.105 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 80°C under nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 6-chloro- 4-methoxy-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]qui nazoline (160 mg, 38%) as an oil. LCMS (ES, m/z): 399 [M+H] ⁺ . Synthesis of Intermediate C174

To a stirred mixture of 6-chloro-4-methoxy-2-[6-(methoxymethoxy)-2,7-dimethylindazol -5- yl]quinazoline (90 mg, 0.226 mmol, 1 equiv) and tert-butyl piperazine-1-carboxylate (50.43 mg, 0.271 mmol, 1.2 equiv) in dioxane (2 mL) was added Cs ₂ CO ₃ (221.24 mg, 0.678 mmol, 3 equiv), Xphos (21.51 mg, 0.045 mmol, 0.2 equiv), and Pd2(dba) ₃ (20.66 mg, 0.023 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 80°C under nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ / MeOH (20:1) to afford tert-butyl 4-{4-methoxy-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl] quinazolin-6- yl}piperazine-1-carboxylate (90 mg, 73%) as a solid. LCMS (ES, m/z): 549 [M+H] ⁺ . To a stirred solution of tert-butyl 4-{4-methoxy-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5- yl]quinazolin-6-yl}piperazine-1-carboxylate (90 mg, 0.164 mmol, 1 equiv) in DCM (1 mL) was added TFA (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 13, Gradient 1) to afford 5-[4-methoxy-6-(piperazin-1- yl)quinazolin-2-yl]-2,7-dimethylindazol-6-ol (21.5 mg, 32%) as a solid. LCMS (ES, m/z): 405 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 13.λ6 (s, 1H), 8.86 (s, 1H), 8.40 (s, 1H), 7.87 (d, J = 9.2 Hz, 1H), 7.80 (dd, J = 9.3, 2.7 Hz, 1H), 7.31 (d, J = 2.6 Hz, 1H), 4.30 (s, 3H), 4.15 (s, 3H), 3.30 (t, J = 5.1 Hz, 4H), 2.97 (t, J = 5.0 Hz, 4H), 2.39 (s, 3H). Example 171: Synthesis of Compound 502 Synthesis of Intermediate C175 To a stirred solution of ethyl 6-[4-(tert-butoxycarbonyl)piperazin-1-yl]-2-[6-(methoxymetho xy)- 2,7-dimethylindazol-5-yl]quinazoline-4-carboxylate (160 mg, 0.271 mmol, 1 equiv) in dimethylamine (2 M in ethanol) (8 mL) at room temperature. The resulting mixture was stirred overnight at 60 °C, then concentrated under reduced pressure to afford tert-butyl 4-[4- (dimethylcarbamoyl)-2-[6-(methoxymethoxy)-2,7-dimethylindazo l-5-yl]quinazolin-6- yl]piperazine-1-carboxylate (75 mg, 47%) as a solid. LCMS (ES, m/z): 590 [M+H] ⁺ . Synthesis of Compound 502 To a stirred solution of tert-butyl 4-[4-(dimethylcarbamoyl)-2-[6-(methoxymethoxy)-2,7- dimethylindazol-5-yl]quinazolin-6-yl]piperazine-1-carboxylat e (75 mg, 0.127 mmol, 1 equiv) in dioxane (1 mL) was added HCl (gas) in 1,4-dioxane (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 13, Gradient 2) to afford 2- (6-hydroxy-2,7-dimethylindazol-5-yl)-N,N-dimethyl-6-(piperaz in-1-yl)quinazoline-4- carboxamide (20.2 mg, 36%) as a solid. LCMS (ES, m/z): 446 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.37 (s, 1H), 8.83 (s, 1H), 8.40 (s, 1H), 8.04 – 7.93 (m, 2H), 6.91 (d, J = 2.5 Hz, 1H), 4.15 (s, 3H), 3.25 (t, J = 5.0 Hz, 4H), 3.20 (s, 3H), 2.90 (d, J = 9.1 Hz, 7H), 2.40 (s, 3H). Example 172: Synthesis of Compound 503 Synthesis of Intermediate C176 To a stirred mixture of ethyl 6-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5- yl]quinazoline-4-carboxylate (200 mg, 0.454 mmol, 1 equiv) and tert-butyl piperazine-1- carboxylate (92.94 mg, 0.499 mmol, 1.1 equiv) in dioxane (4 mL) was added Cs2CO ₃ (221.71 mg, 0.681 mmol, 1.5 equiv), Xphos (43.25 mg, 0.091 mmol, 0.2 equiv), and Pd2(dba) ₃ (41.54 mg, 0.045 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 80 °C under nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ / MeOH (20:1) to afford ethyl 6-[4-(tert-butoxycarbonyl)piperazin-1-yl]-2-[6- (methoxymethoxy)-2,7-dimethylindazol-5-yl]quinazoline-4-carb oxylate (170 mg, 63%) as a solid. LCMS (ES, m/z): 591 [M+H] ⁺ . A mixture of ethyl 6-[4-(tert-butoxycarbonyl)piperazin-1-yl]-2-[6-(methoxymetho xy)-2,7- dimethylindazol-5-yl]quinazoline-4-carboxylate (80 mg, 0.135 mmol, 1 equiv) in ethylamine solution (2.0 M in THF 8 mL) stirred overnight at 80 °C. The resulting mixture was concentrated under reduced pressure to afford tert-butyl 4-[4-(ethylcarbamoyl)-2-[6-(methoxymethoxy)-2,7- dimethylindazol-5-yl]quinazolin-6-yl]piperazine-1-carboxylat e (75 mg, 94%) as a solid. LCMS (ES, m/z): 590 [M+H] ⁺ . Synthesis of Compound 503 To a stirred solution of tert-butyl 4-[4-(ethylcarbamoyl)-2-[6-(methoxymethoxy)-2,7- dimethylindazol-5-yl]quinazolin-6-yl]piperazine-1-carboxylat e (75 mg, 0.127 mmol, 1 equiv) in dioxane (1 mL) was added HCl (gas) in 1,4-dioxane (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 13, Gradient 3) to afford N- ethyl-2-(6-hydroxy-2,7-dimethylindazol-5-yl)-6-(piperazin-1- yl)quinazoline-4-carboxamide (15.5 mg, 27%) as a solid. LCMS (ES, m/z): 446 [M+H] ⁺ . ¹ H NMR (400 MHz, Methanol-d ₄ ) δ 8.95 (d, J = 0.8 Hz, 1H), 8.21 – 8.15 (m, 2H), 7.85 (d, J = 1.5 Hz, 2H), 4.18 (s, 3H), 3.60 (q, J = 7.2 Hz, 2H), 3.38 (t, J = 5.1 Hz, 4H), 3.07 (t, J = 5.1 Hz, 4H), 2.47 (s, 3H), 1.39 (t, J = 7.3 Hz, 3H). Example 173: Synthesis of Compound 484 Synthesis of Intermediate C178 To a stirred solution of methyl 2-amino-4-methylbenzoate (25.0 g, 151.339 mmol, 1.0 equiv) in acetonitrile (500 mL) was added NIS (51.0 g, 227.008 mmol, 1.5 equiv) in portions at room temperature. The resulting mixture was stirred for 3 h at room temperature, then diluted with water (500 mL) and extracted with ethyl acetate (2 x 500 mL). The organic layers were combined, washed with brine (1 x 500 mL), dried over anhydrous Na ₂ SO4, and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to afford methyl 2-amino-5-iodo-4- methylbenzoate (35 g, 72%) as a solid. LCMS (ES, m/z): 292 [M+H] ⁺ . Synthesis of Intermediate C179 To a stirred mixture of methyl 2-amino-5-iodo-4-methylbenzoate (30.0 g, 103.062 mmol, 1.0 equiv) and TEA (20.8 g, 206.124 mmol, 2.0 equiv) in DCM (500 mL) was added methyl 3- chloro-3-oxopropanoate (15.4 g, 113.368 mmol, 1.1 equiv) dropwise at 0 °C. The resulting mixture was stirred for 2 h at 0 °C, then diluted with water (500 mL) and extracted with CH ₂ Cl ₂ (2 x 500 mL). The organic layers were combined, washed with brine (1 x 500 mL), dried over anhydrous Na ₂ SO4, and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to afford methyl 5-iodo-2-(3-methoxy-3-oxopropanamido)-4-methylbenzoate (32 g, 72%) as a solid. LCMS (ES, m/z): 392 [M+H] ⁺ . Synthesis of Intermediate C180 A mixture of methyl 5-iodo-2-(3-methoxy-3-oxopropanamido)- 4-methylbenzoate (31.0 g, 79.251 mmol, 1.0 equiv), methanol (600 mL), and MeONa (8.5 g, 158.502 mmol, 2.0 equiv) was stirred for 5 h at 80 °C. A precipitate formed that was collected by filtration and washed with methanol (1 x 100 mL) to afford methyl 6-iodo-7-methyl-2,4-bis(sodiooxy)quinoline-3- carboxylate (30 g, 85%) as a solid. LCMS (ES, m/z): 392 [M+H] ⁺ . Synthesis of Intermediate C181 To a stirred solution of methyl 6-iodo-7-methyl-2,4-bis(sodiooxy)quinoline-3-carboxylate (28.0 g, 69.465 mmol, 1.0 equiv) in dioxane (200 mL) was added HCl (200 mL) dropwise at room temperature. The resulting mixture was stirred for 3 h at 110°C. A precipitate formed that was collected by filtration and washed with 1,4-dioxane (1x50 mL) to 584yrrol 6-iodo-7- methylquinoline-2,4-diol (18 g, 80%) as a solid. LCMS (ES, m/z): 302 [M+H] ⁺ . Synthesis of Intermediate C182 A mixture of 6-iodo-7-methylquinoline-2,4-diol (10.0 g, 33.213 mmol, 1.0 equiv) and phosphorus oxychloride (30 mL) was stirred for 2 h at 80 °C. The resulting mixture was concentrated under reduced pressure, diluted with water (200 mL), and extracted with ethyl acetate (2 x 200 mL). The organic layers were combined, washed with brine (2 x 200 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 2,4-dichloro-6-iodo-7-methylquinoline (5 g, 41%) as a solid. LCMS (ES, ^{m/z): 337 [M+H] +.} Synthesis of Intermediate C183 To a solution of 2,4-dichloro-6-iodo-7-methylquinoline (600.0 mg, 1.775 mmol, 1.0 equiv) and tert-butyl piperazine-1-carboxylate (495.9 mg, 2.662 mmol, 1.5 equiv) in dioxane (12 mL) was added Cs2CO ₃ (1156.8 mg, 3.550 mmol, 2.0 equiv), Pd2(dba) ₃ (162.5 mg, 0.177 mmol, 0.1 equiv), and 1,2,3,4,5-pentaphenyl-1’-(di-tert-butylphosphino)ferrocene (378.5 mg, 0.532 mmol, 0.3 equiv). The reaction mixture was stirred overnight at 80 °C under a nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford tert-butyl 4-(2,4-dichloro-7- methylquinolin-6-yl) piperazine-1-carboxylate (400 mg, 52%) as a solid. LCMS (ES, m/z): 396 [M+H] ⁺ . Synthesis of Intermediate C184 To a mixture of tert-butyl 4-(2,4-dichloro-7-methylquinolin-6-yl)piperazine-1-carboxyla te (140.0 mg, 0.353 mmol, 1.0 equiv) and 6-(methoxymethoxy)-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2 - dioxaborolan-2-yl)indazole (117.3 mg, 0.353 mmol, 1.0 equiv) in dioxane (4 mL) and water (1 ^{mL) was added K} 3 ^PO 4 ^{(149.9 mg, 0.706 mmol, 2.0 equiv) and Pd(dppf)Cl} 2 ^{(25.8 mg, 0.035} mmol, 0.1 equiv). The reaction mixture was stirred for 3 h at 60 °C under a nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to afford tert-butyl 4-{4-chloro-2-[6- (methoxymethoxy)-2,7-dimethylindazol-5-yl]-7-methylquinolin- 6-yl}piperazine-1-carboxylate (60 mg, 28%) as a solid. LCMS (ES, m/z): 566 [M+H] ⁺ . Synthesis of Compound 484 To a stirred solution of tert-butyl 4-{4-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5- yl]-7 -methylquinolin-6-yl}piperazine-1-carboxylate (60.0 mg, 0.106 mmol, 1.0 equiv) in DCM (1 mL) was added TFA (0.5 mL) dropwise at room temperature. The resulting mixture was stirred for 1 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (SunFire Prep Column19*150 mm,10nm, mobile phase, MeCN in water (0.05% NH4OH), 30% to 50% gradient in 7 min; detector, UV 254 nm) to afford 5-[4-chloro-7-methyl-6-(piperazin-1-yl)586yrrolidi-2-yl]-2,7 -dimethylindazol -6-ol (15.5 mg, 34%) as a solid. LCMS (ES, m/z): 422 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.26 (s, 1H), 8.57 (d, J = 9.8 Hz, 2H), 8.38 (s, 1H), 7.96 (s, 1H), 7.54 (s, 1H), 4.15 (s, 3H), 2.96 (d, J = 4.3 Hz, 8H), 2.50 (s, 3H), 2.39 (s, 3H). Example 174: Synthesis of Compound 486 Synthesis of Intermediate C185 To a mixture of 2,4-dichloro-6-iodo-7-methylquinoline (1.3 g, 3.846 mmol, 1.0 equiv) and tert- butyl N-(586yrrolidine-3-yl)carbamate (0.7 g, 3.846 mmol, 1.0 equiv) in dioxane (20 mL) was added t-BuONa (0.74 g, 7.692 mmol, 2.0 equiv), Xantphos (444.5 mg, 0.769 mmol, 0.2 equiv), and Pd ₂ (dba) ₃ (352.6 mg, 0.385 mmol, 0.1 equiv). The reaction mixture was stirred for 5 h at 80 °C under a nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to afford tert-butyl N-[1-(2,4-dichloro-7-methylquinolin-6-yl)587yrrolidine-3-yl] carbamate (600 mg, 35%) as a solid. LCMS (ES, m/z): 396 [M+H] ⁺ . Synthesis of Intermediate C186 To a stirred mixture of tert-butyl N-[1-(2,4-dichloro-7-methylquinolin-6-yl)587yrrolidine-3- yl]carbamate (580.0 mg, 1.464 mmol, 1 equiv) and NaH (70.2 mg, 2.928 mmol, 2.0 equiv) in DMF (10 mL) was added CH ₃ I (415.4 mg, 2.928 mmol, 2.0 equiv) dropwise at room temperature. The resulting mixture was stirred for 1 h at 0 °C, then quenched with saturated NH ₄ Cl (aq.) (50 mL) at 0 °C and extracted with ethyl acetate (2 x 50 mL). The organic layers were combined, washed with water (1 x 50 mL), brine (1 x 50 mL), dried over anhydrous Na ₂ SO4, and filtered. The filtrate was concentrated under reduced pressure to afford tert-butyl N- [1-(2,4-dichloro-7-methylquinolin-6-yl) 587yrrolidine-3-yl]-N-methylcarbamate (450 mg, 64%) as a solid. LCMS (ES, m/z): 410 [M+H] ⁺ . Synthesis of Intermediate C187 To a mixture of tert-butyl N-[1-(2,4-dichloro-7-methylquinolin-6-yl)587yrrolidine-3-yl] -N- methylcarbamate (200.0 mg, 0.487 mmol, 1.0 equiv) and 6-(methoxymethoxy)-2,7-dimethyl-5- (4,4,5,5-tetramethyl-1,3,2- 587yrrolidine587e-2-yl)indazole (161.9 mg, 0.487 mmol, 1 equiv) in dioxane (4 mL) and water (1 mL) was added K ₃ PO ₄ (206.9 mg, 0.974 mmol, 2 equiv) and Pd(PPh ₃ ) ₄ (56.3 mg, 0.049 mmol, 0.1 equiv). The reaction mixture was stirred for 3 h at 60 °C under a nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford tert-butyl N-(1-{4-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-y l]-7-methylquinolin- 6-yl}588yrrolidine-3-yl)-N-methylcarbamate (150 mg, 48%) as a solid. LCMS (ES, m/z): 580 [M+H] ⁺ . Synthesis of Compound 486 To a stirred solution of tert-butyl N-(1-{4-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol- 5-yl]- 7-methylquinolin-6-yl}588yrrolidine-3-yl)-N-methylcarbamate (200.0 mg, 0.345 mmol, 1.0 equiv) in DCM (2 mL) was added TFA (0.5 mL) dropwise at room temperature. The resulting mixture was stirred for 1 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 14, Gradient 1) to afford 5-{4-chloro-7-methyl-6-[3-(methylamino)pyrrolidin-1-yl]quino lin-2-yl} -2,7- dimethylindazol-6-ol (40 mg, 26%) as a solid. LCMS (ES, m/z): 436 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.34 (s, 1H), 8.50 (s, 1H), 8.46 (s, 1H), 8.35 (s, 1H), 7.85 (d, J = 1.0 Hz, 1H), 7.16 (s, 1H), 4.15 (s, 3H), 3.60 (dd, J = 9.4, 5.9 Hz, 1H), 3.58-3.48 (m, 1H), 3.47-3.37 (m, 1H), 3.23 (dd, J = 9.4, 4.6 Hz, 1H), 2.58 (s, 3H), 2.38 (s, 3H), 2.35 (s, 3H), 2.13 (dq, J = 13.0, 6.6 Hz, 1H), 1.83 (dq, J = 12.6, 6.4 Hz, 1H). Example 175: Synthesis of Compound 530 Synthesis of Intermediate C188 A mixture of ethyl 2,6-dichloroquinazoline-4-carboxylate (500 mg, 1.844 mmol, 1 equiv), 6- (methoxymethoxy)-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)indazole (942.2 mg, 2.961 mmol, 1.61 equiv), Pd(PPh3)4 (214 mg, 0.185 mmol, 0.10 equiv), and K3PO4 (783 mg, 3.689 mmol, 2.00 equiv) in dioxane (20 mL, 236.079 mmol, 128.00 equiv) and water (0.2 mL, 11.102 mmol, 6.02 equiv) was stirred for 2 h at 80 °C under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:1) to afford ethyl 6-chloro-2-[6- (methoxymethoxy)-2-methylindazol-5-yl]quinazoline-4-carboxyl ate (550 mg, 70%) as a solid. LCMS (ES, m/z): 427 [M+H] ⁺ . Synthesis of Intermediate C189 A mixture of ethyl 6-chloro-2-[6-(methoxymethoxy)-2-methylindazol-5-yl]quinazol ine-4- carboxylate (250 mg, 0.586 mmol, 1 equiv), tert-butyl (2S)-2-methylpiperazine-1-carboxylate (176 mg, 0.879 mmol, 1.50 equiv), Pd2(dba) ₃ (53.7 mg, 0.059 mmol, 0.10 equiv), RuPhos (54.8 mg, 0.117 mmol, 0.20 equiv), and Cs ₂ CO ₃ (382.6 mg, 1.174 mmol, 2.00 equiv) in dioxane (5 mL) was stirred for 2 h at 80°C under nitrogen atmosphere, then cooled to room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE/EA (1:1) to afford ethyl 6- [(3S)-4-(tert-butoxycarbonyl)-3-methylpiperazin-1-yl]-2-[6-( methoxymethoxy)-2-methylindazol- 5-yl]quinazoline-4-carboxylate (300 mg, 87%) as a solid. LCMS (ES, m/z): 591 [M+H] ⁺ . Synthesis of Intermediate C190

A mixture of 2M CH ₃ NH ₂ solution in methanol (0.5 mL) and ethyl 6-[(3S)-4-(tert- butoxycarbonyl)-3-methylpiperazin-1-yl]-2-[6-(methoxymethoxy )-2-methylindazol-5- yl]quinazoline-4-carboxylate (50 mg, 0.085 mmol, 1 equiv) was stirred for 1 h at 80°C. The resulting mixture was concentrated under reduced pressure to afford tert-butyl (S)-4-(2-(6- (methoxymethoxy)-2-methyl-2H-indazol-5-yl)-4-(methylcarbamoy l)quinazolin-6-yl)-2- methylpiperazine-1-carboxylate (45 mg) as an oil. LCMS (ES, m/z): 276 [M+H] ⁺ . A solution of TFA (0.15 mL) in DCM (0.5 mL) was treated with tert-butyl (2S)-4-{2-[6- (methoxymethoxy)-2-methylindazol-5-yl]-4-(methylcarbamoyl)qu inazolin-6-yl}-2- methylpiperazine-1-carboxylate (50 mg, 0.087 mmol, 1.00 equiv). The reaction mixture was stirred for 15 min at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by reverse phase flash chromatography (Condition 10, Gradient 8) to afford 2-(6-hydroxy-2-methylindazol-5-yl)-N-methyl-6-[(3S)-3-methyl piperazin- 1-yl]quinazoline-4-carboxamide (18.1 mg, 48%) as a solid. LCMS (ES, m/z): 432 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.21 (s, 1H), λ.23 (s, 2H), 8.45 (s, 1H), 8.16 (s, 1H), 7.λλ (s, 2H), 6.91 (s, 1H), 4.14 (s, 3H), 3.78 (t, J = 12.3 Hz, 2H), 3.10 (d, J = 11.5 Hz, 1H), 3.07-2.75 (m, 6H), 1.12 (d, J = 6.3 Hz, 3H). Example 176: Synthesis of Compound 532 Synthesis of Intermediate C191 To a mixture of ethyl 6-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]quin azoline-4- carboxylate (200 mg, 0.454 mmol, 1 equiv) and tert-butyl 4,7-diazaspiro[2.5]octane-4- carboxylate (144 mg, 0.681 mmol, 1.5 equiv) in dioxane (4 mL) was added Cs ₂ CO ₃ (443 mg, 1.362 mmol, 3.0 equiv), RuPhos (42.3 mg, 0.091 mmol, 0.2 equiv), and Pd2(dba) ₃ (41 mg, 0.045 mmol, 0.1 equiv). The reaction mixture was stirred for 1 h at 90 °C under a nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by reverse- phase flash chromatography (Condition 10, Gradient 8) to afford ethyl 6-[4-(tert- butoxycarbonyl)-4,7-diazaspiro[2.5]octan-7-yl]-2-[6-(methoxy methoxy)-2,7-dimethylindazol-5- yl]quinazoline-4-carboxylate (250 mg, 89%) as a solid. LCMS (ES, m/z): 617 [M+H] ⁺ . Synthesis of Intermediate C192 A mixture of ethyl 6-[4-(tert-butoxycarbonyl)-4,7-diazaspiro[2.5]octan-7-yl]-2- [6- (methoxymethoxy)-2,7-dimethylindazol-5-yl]quinazoline-4-carb oxylate (250 mg, 0.405 mmol, 1 equiv) and 2M CH ₃ NH ₂ in methanol (4 mL) was stirred for 1 h at 80 °C. The resulting mixture was concentrated under reduced pressure to afford (230 mg) as a solid. LCMS (ES, m/z): 602 [M+H] ⁺ . Synthesis of Compound 532

A solution of tert-butyl 7-{2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]-4- (methylcarbamoyl)quinazolin-6-yl}-4,7-diazaspiro[2.5]octane- 4-carboxylate (200 mg, 0.332 mmol, 1 equiv) in DCM (4 mL) was treated with 4 M HCl (gas) in 1,4-dioxane (4 mL) for 1 h at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by reverse flash chromatography (Condition 10, Gradient 9) to afford 6-{4,7-diazaspiro[2.5]octan-7-yl}-2-(6-hydroxy-2,7-dimethyli ndazol-5-yl)-N- methylquinazoline-4-carboxamide (70 mg, 46%) as a solid. LCMS (ES, m/z): 458 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d6) δ 13.40 (s, 1H), λ.21 (d, J = 5.0 Hz, 1H), 9.10 (d, J = 0.8 Hz, 1H), 8.42 (s, 1H), 8.12 (d, J = 2.3 Hz, 1H), 8.06-7.92 (m, 2H), 4.17 (s, 3H), 3.39 (s, 2H), 3.28 (s, 2H), 3.10 (d, J = 5.5 Hz, 2H), 2.97 (d, J = 4.8 Hz, 3H), 2.41 (s, 3H), 0.71 (s, 4H). Example 177: Synthesis of Compound 536 Synthesis of Intermediate C193 To a stirred mixture of ethyl 6-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5- yl]quinazoline-4-carboxylate (200 mg, 0.454 mmol, 1 equiv) and tert-butyl N-methyl-N-[(3R)- pyrrolidin-3-yl]carbamate (136 mg, 0.681 mmol, 1.5 equiv) in 1,4-dioxane (4 mL) was added Cs ₂ CO ₃ (443 mg, 1.362 mmol, 3 equiv), RuPhos (42 mg, 0.091 mmol, 0.2 equiv), and Pd ₂ (dba) ₃ (41 mg, 0.045 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 h at 100°C, then cooled to room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford ethyl 6-[(3R)-3-[(tert- butoxycarbonyl)(methyl)amino]pyrrolidin-1-yl]-2-[6-(methoxym ethoxy)-2,7-dimethylindazol-5- yl]quinazoline-4-carboxylate (200 mg, 73%) as a solid. LCMS (ES, m/z): 605 [M+H] ⁺ . Synthesis of Intermediate C194 A mixture of ethyl 6-[(3R)-3-[(tert-butoxycarbonyl)(methyl)amino]pyrrolidin-1-y l]-2-[6- (methoxymethoxy)-2,7-dimethylindazol-5-yl]quinazoline-4-carb oxylate (160 mg, 0.265 mmol, 1 equiv) and 2 M MeNH ₂ solution in methanol (2 mL) was stirred for 3 h at 90 °C, then cooled to room temperature. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford tert-butyl N-[(3R)-1-{2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]-4 - (methylcarbamoyl)quinazolin-6-yl}pyrrolidin-3-yl]-N-methylca rbamate (150 mg, 96%) as a solid. LCMS (ES, m/z): 590 [M+H] ⁺ . To a stirred solution of tert-butyl N-[(3R)-1-{2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]- 4-(methylcarbamoyl)quinazolin-6-yl}pyrrolidin-3-yl]-N-methyl carbamate (150 mg, 0.254 mmol, 1 equiv) in DCM (1.5 mL) was added TFA (0.5 mL) at room temperature. The resulting mixture was stirred for 2 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by reversed-phase flash chromatography (Condition 10, Gradient 10) to afford 2-(6-hydroxy-2,7-dimethylindazol-5-yl)-N-methyl-6-[(3R)-3- (methylamino)pyrrolidin-1-yl]quinazoline-4-carboxamide (50 mg, 44%) as a solid. LCMS (ES, m/z): 446 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d6) δ 13.45 (s, 1H), λ.16 (d, J = 5.1 Hz, 1H), 9.05 (s, 1H), 8.40 (s, 1H), 8.00 (d, J = 9.3 Hz, 1H), 7.77 (d, J = 2.7 Hz, 1H), 7.65-7.56 (m, 1H), 4.16 (s, 3H), 3.63 (s, 3H), 3.57 (d, J = 8.1 Hz, 3H), 3.45 (d, J = 7.7 Hz, 1H), 2.97 (d, J = 4.7 Hz, 3H), 2.48 (s, 2H), 2.41 (s, 3H), 2.28 (s, 1H), 2.08 (s, 1H). Example 178: Synthesis of Compound 723 Synthesis of Intermediate C195 To a stirred mixture of 2,4-dichloro-6-iodo-8-methylquinoline (300 mg, 0.888 mmol, 1.0 equiv) and tert-butyl (2R,6S)-2,6-dimethylpiperazine-1-carboxylate (190.2 mg, 0.888 mmol, 1.0 equiv) in dioxane (3 mL) was added Cs2CO ₃ (578.4 mg, 1.776 mmol, 2.0 equiv), Q-phos (62.9 mg, 0.089 mmol, 0.1 equiv), and Pd2(dba) ₃ (81.2 mg, 0.089 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 6 h at 80 °C under nitrogen atmosphere, then cooled to room temperature, diluted with water (10 mL), and extracted with ethyl acetate (3 x10 mL). The organic layers were combined, washed with brine (1 x 10 mL), dried over anhydrous Na ₂ SO4, and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with EA to afford tert-butyl (2R,6S)-4-(2,4-dichloro-8-methylquinolin-6-yl)-2,6-dimethylp iperazine-1- carboxylate (180 mg, 48%) as a solid. LCMS (ES, m/z): 424 [M+H] ⁺ . Synthesis of Intermediate C196

To a stirred mixture of tert-butyl (2R,6S)-4-(2,4-dichloro-8-methylquinolin-6-yl)-2,6- dimethylpiperazine-1-carboxylate (180 mg, 0.424 mmol, 1.0 equiv) and 7-fluoro-6- (methoxymethoxy)-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)indazole (142.5 mg, 0.424 mmol, 1.0 equiv) in dioxane (1.5 mL) and water (0.3 mL) was added K ₃ PO ₄ (180.0 mg, 0.848 mmol, 2.0 equiv) and Pd(PPh ₃ ) ₄ (49.0 mg, 0.042 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 80 °C under nitrogen atmosphere, then cooled to room temperature, diluted with water (10 mL), and extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, washed with brine (1 x 10 mL), dried over anhydrous Na ₂ SO4, and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with EA to afford tert-butyl (2R,6S)-4-{4-chloro-2-[7-fluoro-6-(methoxymethoxy)-2-methyli ndazol-5-yl]- 8-methylquinolin-6-yl}-2,6-dimethylpiperazine-1-carboxylate (124 mg, 49%) as a solid. LCMS (ES, m/z): 598 [M+H] ⁺ . Synthesis of Compound 723 A solution of tert-butyl (2R,6S)-4-{4-chloro-2-[7-fluoro-6-(methoxymethoxy)-2-methyli ndazol- 5-yl]-8-methylquinolin-6-yl}-2,6-dimethylpiperazine-1-carbox ylate (120 mg, 0.201 mmol, 1 equiv) in DCM (1 mL) was treated with TFA (0.25 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature under nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 6, Gradient 6) to afford 5-{4-chloro-6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-8-methylq uinolin-2- yl}-7-fluoro-2-methylindazol-6-ol (62 mg, 55%) as a solid. LCMS (ES, m/z): 454 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 14.72 (s, 1H), 8.54 (d, J = 8.5 Hz, 2H), 8.50 (d, J = 2.6 Hz, 1H), 7.87-7.55 (m, 1H), 7.10 (d, J = 2.6 Hz, 1H), 4.17 (s, 3H), 3.80 (dd, J = 11.7, 2.8 Hz, 2H), 2.88- 2.87 (m, 2H), 2.68 (s, 3H), 2.37-2.19 (m, 3H), 1.08 (d, J = 6.2 Hz, 6H). Example 179: Synthesis of Compound 538 Synthesis of Intermediate C197 To a stirred mixture of 2,4,6-trichloroquinazoline (2.5 g, 10.708 mmol, 1.0 equiv) and trimethylsilylacetylene (1.05 g, 10.708 mmol, 1.0 equiv) in THF (50 mL) was added Et ₃ N (3.25 g, 32.124 mmol, 3.0 equiv) and bis(triphenylphosphane)dichloropalladium (0.75 g, 1.071 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 h at room temperature under nitrogen atmosphere, then extracted with ethyl acetate (3 x 50 mL). The organic layers were combined, washed with brine (1 x 20 mL), dried over anhydrous Na ₂ SO4, and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (15:1) to afford 2,6-dichloro-4-[2-(trimethylsilyl)ethynyl]quinazoline (510 mg, 16%) as a solid. LCMS (ES, m/z): 395 [M+H] ⁺ . Synthesis of Intermediate C198

A solution of 2,6-dichloro-4-[2-(trimethylsilyl)ethynyl]quinazoline (470 mg, 1.592 mmol, 1.0 equiv) in THF (5 mL) was treated with K ₂ CO ₃ (220.0 mg, 1.592 mmol, 1.0 equiv) at 0°C. The resulting mixture was stirred for 2 h at 0°C under nitrogen atmosphere, then diluted with water (10 mL) and extracted with EtOAc (3 x 15 mL). The organic layers were combined, washed with water (1 x20 mL) and brine (1 x 20 mL), dried over anhydrous Na ₂ SO4, and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (4:1) to afford 2,6-dichloro-4-ethynylquinazoline (168 mg, 47%) as a solid. LCMS (ES, m/z): 223 [M+H] ⁺ . Synthesis of Intermediate C199 To a stirred mixture of 2,6-dichloro-4-ethynylquinazoline (162 mg, 0.628 mmol, 1.0 equiv) and 1-(azidomethyl)-4-methoxybenzene (204.8 mg, 1.256 mmol, 2.0 equiv) in tert-butanol (1.4 mL) and water (0.7 mL) was added CuSO ₄ (10.02 mg, 0.063 mmol, 0.1 equiv) and sodium ascorbate (24.99 mg, 0.126 mmol, 0.2 equiv) at room temperature. The resulting mixture was stirred for 2 h at 60°C under nitrogen atmosphere, then cooled to room temperature, diluted with water (40 mL), and extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, washed with water (1 x 20 mL) and brine (1 x 20 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 2,6-dichloro-4-{1-[(4- methoxyphenyl)methyl]-1,2,3-triazol-4-yl}quinazoline (140 mg, 58%) as a solid. LCMS (ES, m/z): 386 [M+H] ⁺ . Synthesis of Intermediate C200 To a stirred mixture of 2,6-dichloro-4-{1-[(4-methoxyphenyl)methyl]-1,2,3-triazol-4- yl}quinazoline (123 mg, 0.318 mmol, 1.0 equiv) and 6-(methoxymethoxy)-2,7-dimethyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazole (126.9 mg, 0.382 mmol, 1.2 equiv) in dioxane (1 mL) and water (0.2 mL) was added K ₂ CO ₃ (88.0 mg, 0.636 mmol, 2 equiv) and Pd(dppf)Cl ₂ (23.3 mg, 0.032 mmol, 0.1 equiv) at room temperature. The resulting mixture was stirred for 3 h at 80°C under nitrogen atmosphere, then cooled to room temperature and concentrated under vacuum to give a reside. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:2) to afford 6-chloro-2-[6-(methoxymethoxy)-2,7- dimethylindazol-5-yl]-4-{1-[(4-methoxyphenyl)methyl]-1,2,3-t riazol-4-yl}quinazoline (136 mg, 77%) as a solid. LCMS (ES, m/z): 556 [M-H] ⁺ . Synthesis of Intermediate C201 To a stirred mixture of 6-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]-4-{ 1-[(4- methoxyphenyl)methyl]-1,2,3-triazol-4-yl}quinazoline (120 mg, 0.216 mmol, 1.0 equiv) and tert-butyl piperazine-1-carboxylate (48.2 mg, 0.259 mmol, 1.2 equiv) in dioxane (2.4 mL) was added Ruphos (20.1 mg, 0.043 mmol, 0.2 equiv), Cs2CO ₃ (140.6 mg, 0.432 mmol, 2 equiv), and RuPhos Palladacycle Gen.3 (18.0 mg, 0.022 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 110 C under nitrogen atmosphere, then cooled to room temperature, diluted with water (40 mL), and extracted with ethyl acetate (3 x 50 mL). The organic layers were combined, washed with brine (1 x 30 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to afford tert-butyl 4-{2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]-4-{1-[(4- methoxyphenyl)methyl]-1,2,3-triazol-4-yl}quinazolin-6-yl}pip erazine-1-carboxylate(152 mg, 88%) as a solid. LCMS (ES, m/z): 706 [M+H] ⁺ . Synthesis of Compound 538 A mixture of tert-butyl 4-{2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]-4-{1-[(4- methoxyphenyl)methyl]-1,2,3-triazol-4-yl}quinazolin-6-yl}pip erazine-1-carboxylate (150 mg, 0.213 mmol, 1 equiv) and TFA (2 mL) was stirred for 4 h at 70 °C under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 8, Gradient 2) to afford 2,7-dimethyl-5-[6-(piperazin-1- yl)-4-(1H-1,2,3-triazol-4-yl)quinazolin-2-yl]indazol-6-ol hydrochloride (32 mg, 23%) as a solid. LCMS (ES, m/z): 442 [M+H] ⁺ . ¹ H NMR (300 MHz, D2O+CD3CN) δ 8.λ6 (s, 1H), 8.λ0 (s, 1H), 8.69 (s, 1H), 8.44 (s, 1H), 8.05 (s, 2H), 4.45 (s, 3H), 3.90 (d, J = 5.9 Hz, 4H), 3.77 (d, J = 5.7 Hz, 4H), 2.48 (s, 3H). Example 180: Synthesis of Compound 533 Synthesis of Intermediate C202 A solution of 3-amino-6-chloropyridine-2-carboxylic acid (10 g, 57.947 mmol, 1.0 equiv) in methanol (100 mL) was treated with SOCl ₂ (6.89 g, 57.947 mmol, 1.0 equiv) at room temperature. The resulting mixture was stirred overnight at 80 °C, then cooled to room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was neutralized to pH 7 with saturated Na ₂ CO ₃ (aq.) and extracted with CH ₂ Cl ₂ (2 x 150 mL). The organic layers were combined, washed with water (1 x 100 mL) and brine (1 x 100 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. The filtrate was concentrated under reduced pressure to afford methyl 3-amino-6-chloropyridine-2-carboxylate (9.7 g, 90%) as a solid. LCMS (ES, m/z): 187 [M+H] ⁺ . Synthesis of Intermediate C203 To a stirred solution of methyl 3-amino-6-chloropyridine-2-carboxylate (9.7 g, 51.983 mmol, 1.0 equiv) in THF (100 mL) was added trichloroethanecarbonyl isocyanate (9.79 g, 51.983 mmol, 1.0 equiv) dropwise at 0 °C under nitrogen atmosphere. The resulting mixture was stirred for 2 h at room temperature under nitrogen atmosphere, then diluted with diethyl ether (150 mL). A precipitate formed that was collected by filtration and washed with diethyl ether (1 x 20 mL). The resulting solid was dried to afford methyl 6-chloro-3-{[(2,2,2- trichloroacetyl)carbamoyl]amino}pyridine-2-carboxylate (19.2 g, 99%) as a solid. LCMS (ES, m/z): 374 [M+H] ⁺ . Synthesis of Intermediate C204 A mixture of methyl 6-chloro-3-{[(2,2,2-trichloroacetyl)carbamoyl]amino}pyridine -2- carboxylate (19.2 g, 51.203 mmol, 1.0 equiv) and NH ₃ (g) in methanol (1.45 mL, 51.203 mmol, 1 equiv) (7M) in methanol (250 mL) was stirred for 2 h at room temperature. The resulting mixture was heated to 70°C and stirred for an additional 3 h. A precipitate formed that was collected by filtration and washed with methanol (1x50 mL). The resulting solid was dried to afford 6- chloropyrido[3,2-d]pyrimidine-2,4-diol (9.2 g, 91%) as a solid. LCMS (ES, m/z): 198 [M+H] ⁺ . Synthesis of Intermediate C205 A solution of 6-chloropyrido[3,2-d]pyrimidine-2,4-diol (9 g, 45.551 mmol, 1.0 equiv) in POCl ₃ (69.84 g, 455.510 mmol, 10.0 equiv) was treated with DIEA (23.55 g, 182.204 mmol, 4.0 equiv) at room temperature. The resulting mixture was stirred for 16 h at 100 °C, then cooled to room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to afford 2,4,6-trichloropyrido[3,2-d]pyrimidine (3.8 g, 36%) as a solid. LCMS (ES, m/z): 234 [M+H] ⁺ . Synthesis of Intermediate C206 To a stirred mixture of 2,4,6-trichloropyrido[3,2-d]pyrimidine (3.6 g, 15.354 mmol, 1.0 equiv) and tributyl(1-ethoxyethenyl)stannane (5.55 g, 15.354 mmol, 1.0 equiv) in DMF (24 mL) was added palladium chloride; bis(triphenylphosphine) (1.08 g, 1.535 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 h at 60°C under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. The resulting mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with water (1 x 20 mL) and brine (1 x 20 mL), dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to afford 2,6-dichloro-4-(1-ethoxyethenyl)pyrido[3,2- d]pyrimidine (2.4 g, 60 %) as a light yellow solid. LCMS (ES, m/z): 270 [M+H] ⁺ . Synthesis of Intermediate C207 A solution of 2,6-dichloro-4-(1-ethoxyethenyl)pyrido[3,2-d]pyrimidine (2.2 g, 8.145 mmol, 1.0 equiv) in dioxane (22 mL) was treated with NaIO ₄ (3.48 g, 16.290 mmol, 2.0 equiv) in water (10 mL) at room temperature under nitrogen atmosphere followed by the addition of KMnO ₄ (643.5 mg, 4.072 mmol, 0.5 equiv) in portions at room temperature. The resulting mixture was stirred for 2 h at room temperature under nitrogen atmosphere, then extracted with ethyl acetate (3 x 50 mL). The organic layers were combined, washed with brine (1 x 20 mL), dried over anhydrous Na ₂ SO4, and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (4:1) to afford ethyl 2,6-dichloropyrido[3,2-d]pyrimidine-4-carboxylate (750 mg, 34%) as a solid. LCMS (ES, m/z): 272 [M+H] ⁺ . Synthesis of Intermediate C208 To a stirred mixture of ethyl 2,6-dichloropyrido[3,2-d]pyrimidine-4-carboxylate (750 mg, 2.756 mmol, 1.0 equiv) and 6-(methoxymethoxy)-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2 - dioxaborolan-2-yl)indazole (1.0 g, 3.032 mmol, 1.1 equiv) in dioxane (8 mL) and water (2 mL) was added K ₃ PO ₄ (1.17 g, 5.512 mmol, 2.0 equiv) and Pd(PPh ₃ ) ₄ (318.53 mg, 0.276 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 90 °C under nitrogen atmosphere, then cooled to room temperature and concentrated under vacuum to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to afford ethyl 6-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5- yl]pyrido[3,2-d]pyrimidine-4-carboxylate (260 mg, 21%) as a solid. LCMS (ES, m/z): 442 [M+H] ⁺ . Synthesis of Intermediate C209 To a stirred mixture of ethyl 6-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5- yl]pyrido[3,2-d]pyrimidine-4-carboxylate (130 mg, 0.294 mmol, 1.0 equiv) and tert-butyl piperazine-1-carboxylate (54.8 mg, 0.294 mmol, 1.0 equiv) in DMAc (2 mL) was added TEA (89.3 mg, 0.882 mmol, 3.0 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 60°C under nitrogen atmosphere, then cooled to room temperature and concentrated under reduced pressure to give a residue. LCMS (ES, m/z): 592 [M+H] ⁺ . Synthesis of Intermediate C210 To C ₂ 09 was added CH ₃ NH ₂ (1.5 mL, 2M in MeOH) in methanol (10 mL) at room temperature. The resulting mixture was stirred for 2 h at 80°C, then cooled to room temperature and extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, washed with brine (1 x 10 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by Prep-TLC (EA) to afford tert-butyl 4-{2- [6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]-4-(methylcarba moyl)pyrido[3,2-d]pyrimidin-6- yl}piperazine-1-carboxylate (120 mg, 71%) as a solid. LCMS (ES, m/z): 577 [M+H] ⁺ . Synthesis of Compound 533 A solution of tert-butyl 4-{2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]-4- (methylcarbamoyl)pyrido[3,2-d]pyrimidin-6-yl}piperazine-1-ca rboxylate (114 mg, 0.198 mmol, 1.0 equiv) in DCM (1 mL) was treated with TFA (0.25 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 6, Gradient 7) to afford 2-(6-hydroxy-2,7-dimethylindazol-5-yl)-N- methyl-6-(piperazin-1-yl)pyrido[3,2-d]pyrimidine-4-carboxami de (56.8 mg, 66%) as a solid. LCMS (ES, m/z): 433 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d6) δ 13.26 (s, 1H), 8.87 (d, J = 5.0 Hz, 1H), 8.60 (d, J = 9.5 Hz, 1H), 8.45 (s, 1H), 8.36 (s, 1H), 8.05 (d, J = 9.2 Hz, 1H), 4.14 (s, 3H), 3.86 (d, J = 5.7 Hz, 4H), 2.91 (d, J = 4.7 Hz, 3H), 2.81 (t, J = 5.2 Hz, 4H), 2.38 (s, 3H). Example 181: Synthesis of Compound 679 Synthesis of Intermediate C211

To a stirred mixture of ethyl 6-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5- yl]pyrido[3,2-d]pyrimidine-4-carboxylate (120 mg, 0.272 mmol, 1.0 equiv) and tert-butyl (2R,6S)-2,6-dimethylpiperazine-1-carboxylate (67.6 mg, 0.316 mmol, 1.0 equiv) in DMAc (2 mL) was added TEA (95.8 mg, 0.948 mmol, 3.0 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 h at 60°C under nitrogen atmosphere, then cooled to room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. LCMS (ES, m/z): 620 [M+H] ⁺ . To C ₂ 11 was added CH ₃ NH ₂ (1.5 mL, 2M in MeOH) in methanol (10 mL) at room temperature. The resulting mixture was stirred for an additional 3 h at 80 °C, then cooled to room temperature and extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, washed with water (1 x 10mL) and brine (1 x 10 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by Prep- TLC (EA) to afford tert-butyl (2R,6S)-4-{2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]-4 - (methylcarbamoyl)pyrido[3,2-d]pyrimidin-6-yl}-2,6-dimethylpi perazine-1-carboxylate (121 mg) as a solid. LCMS (ES, m/z): 577 [M+H] ⁺ . Synthesis of Compound 679

A solution of tert-butyl (2R,6S)-4-{2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]-4 - (methylcarbamoyl)pyrido[3,2-d]pyrimidin-6-yl}-2,6-dimethylpi perazine-1-carboxylate (121 mg, 0.200 mmol, 1.0 equiv) in DCM (1 mL) was treated with TFA (0.25 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature under nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 6, Gradient 7) to afford 6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-2-(6-hydroxy-2,7- dimethylindazol-5-yl)-N-methylpyrido[3,2-d]pyrimidine-4-carb oxamide (60.2 mg, 65%) as a solid. LCMS (ES, m/z): 461 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 13.25 (s, 1H), 8.87 (d, J = 4.9 Hz, 1H), 8.60 (d, J = 9.5 Hz, 1H), 8.45 (s, 1H), 8.36 (s, 1H), 8.06 (d, J = 9.3 Hz, 1H), 4.72 (d, J = 12.3 Hz, 2H), 4.14 (s, 3H), 2.92 (d, J = 4.7 Hz, 3H), 2.74 (d, J = 8.3 Hz, 2H), 2.48 (d, J = 2.8 Hz, 2H), 2.37 (s, 3H), 1.08 (d, J = 6.2 Hz, 6H). Example 182: Synthesis of Compound 515 Synthesis of Intermediate C213 To a stirred mixture of 6-bromo-8-fluoroquinolin-2-ol (600 mg, 2.479 mmol, 1 equiv) and tert- butyl piperazine-1-carboxylate (692 mg, 3.719 mmol, 1.5 equiv) in 1,4-dioxane (5 mL) was added sodium t-butoxide (476 mg, 4.958 mmol, 2 equiv), Pd ₂ (dba) ₃ (227 mg, 0.248 mmol, 0.1 equiv), and 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphino)ferrocene (352 mg, 0.496 mmol, 0.2 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 100 °C, then cooled to room temperature. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford tert-butyl 4-(8-fluoro-2-hydroxyquinolin-6- yl)piperazine-1-carboxylate (600 mg, 70%) as a solid. LCMS (ES, m/z): 348 [M+H] ⁺ . Synthesis of Intermediate C214 To a stirred mixture of tert-butyl 4-(8-fluoro-2-hydroxyquinolin-6-yl)piperazine-1-carboxylate (200 mg, 0.576 mmol, 1 equiv) and hexafluoro-l[5]-phosphanuide tris(pyrrolidin-1- yl)phosphanium bromide (402 mg, 0.864 mmol, 1.5 equiv) in 1,4-dioxane (5.0 mL) was added K ₂ CO ₃ (238 mg, 1.728 mmol, 3 equiv) and TEA (174 mg, 1.728 mmol, 3 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 100 °C, then cooled to room temperature. To the reaction mixture was added 6-(methoxymethoxy)-2,7- dimethyl-5-(4,4,5-trimethyl-1,3,2-dioxaborolan-2-yl)indazole (219 mg, 0.691 mmol, 1.2 equiv), water (0.5 mL), and Pd(dppf)Cl ₂ (46 mg, 0.058 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for an additional 2 h at 100 °C, then cooled to room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford tert-butyl 4-{8-fluoro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5- yl]quinolin-6-yl}piperazine-1-carboxylate (300 mg, 97%) as a solid. LCMS (ES, m/z): 536 [M+H] ⁺ . To a stirred solution of tert-butyl 4-{8-fluoro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5- yl]quinolin-6-yl}piperazine-1-carboxylate (200 mg, 0.373 mmol, 1 equiv) in DCM (1.5 mL) was added TFA (0.5 mL) at room temperature. The resulting mixture was stirred for 2 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by reverse flash chromatography (Condition 10, Gradient 10) to afford 5-[8-fluoro-6- (piperazin-1-yl)quinolin-2-yl]-2,7-dimethylindazol-6-ol (50 mg, 34%) as a solid. LCMS (ES, m/z): 392 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.4λ (s, 1H), 8.50 (s, 1H), 8.42-8.35 (m, 3H), 8.34 (d, J = 8.6 Hz, 1H), 7.60 (dd, J = 14.3, 2.4 Hz, 1H), 7.10 (d, J = 2.5 Hz, 1H), 4.15 (s, 3H), 3.28 (d, J = 10.0 Hz, 4H), 2.90 (t, J = 5.1 Hz, 4H), 2.39 (s, 3H). Example 183: Synthesis of Compound 516 Synthesis of Intermediate C215 To a stirred mixture of tert-butyl 4-(8-fluoro-2-hydroxyquinolin-6-yl)piperazine-1-carboxylate (200 mg, 0.576 mmol, 1 equiv) and hexafluoro-l^[5]-phosphanuide tris(pyrrolidin-1- yl)phosphanium bromide (402 mg, 0.864 mmol, 1.5 equiv) in 1,4-dioxane (2 mL, 0.023 mmol) was added K ₂ CO ₃ (238 mg, 1.728 mmol, 3 equiv) and TEA (175 mg, 1.728 mmol, 3.0 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 100 °C, then cooled to room temperature. To the reactioin mixture was added 7-fluoro-2-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazole (190mg, 0.691 mmol, 1.2 equiv), water (0.4 mL), and Pd(dppf)Cl ₂ (46 mg, 0.058 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for additional 2 h at 100 °C, then cooled to room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford tert-butyl 4-[8-fluoro-2-(7-fluoro-2-methylindazol-5-yl)quinolin-6-yl]p iperazine-1- carboxylate (200 mg, 72%) as a solid. LCMS (ES, m/z): 480 [M+H] ⁺ . Synthesis of Compound 516 To a stirred solution of tert-butyl 4-[8-fluoro-2-(7-fluoro-2-methylindazol-5-yl)quinolin-6- yl]piperazine-1-carboxylate (150 mg, 0.313 mmol, 1 equiv) in DCM (1.5 mL) was added TFA (0.5 mL) at room temperature. The resulting mixture was stirred for 2 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by reverse flash chromatography (Condition 10, Gradient 10) to afford 8-fluoro-2-(7-fluoro-2- methylindazol-5-yl)-6-(piperazin-1-yl)quinoline (25 mg, 21%) as a solid. LCMS (ES, m/z): 380 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d6) δ 8.63 (d, J = 2.8 Hz, 1H), 8.44 (s, 1H), 8.25 (d, J = 8.2 Hz, 1H), 8.18 (d, J = 8.8 Hz, 1H), 7.99 (dd, J = 13.7, 1.3 Hz, 1H), 7.52 (dd, J = 14.3, 2.5 Hz, 1H), 7.05 (d, J = 2.5 Hz, 1H), 4.24 (s, 3H), 3.27 (t, J = 5.0 Hz, 4H), 2.92 (t, J = 5.0 Hz, 4H). Example 184: Synthesis of Compound 517 Synthesis of Intermediate C216 A mixture of tert-butyl 4-(8-fluoro-2-hydroxyquinolin-6-yl) piperazine-1-carboxylate (200 mg, 0.576 mmol, 1.00 equiv) and Tf2O (32 mg, 1.152 mmol, 2.00 equiv) in pyridine (3 mL) was stirred for 6 h at room temperature. The reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, washed with brine (3 x 10 mL), dried over anhydrous Na ₂ SO4, and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE /EA (10:1) to afford tert-butyl 4-[8-fluoro-2- (trifluoromethanesulfonyloxy)quinolin-6-yl]piperazine-1-carb oxylate (130 mg, 47%) as a solid. LCMS (ES, m/z): 479 [M+H] ⁺ . Synthesis of Intermediate C217 To a stirred mixture of tert-butyl 4-[8-fluoro-2-(trifluoromethanesulfonyloxy)quinolin-6- yl]piperazine-1-carboxylate (130 mg, 0.271 mmol, 1 equiv) and 8-fluoro-2-methyl-6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine (112 mg, 0.407 mmol, 1.5 equiv) in dioxane (2 mL) and water (0.4 mL) was added K ₃ PO ₄ (115 mg, 0.542 mmol, 2.0 equiv) and Pd(PPh ₃ ) ₄ (31 mg, 0.027 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 6 h at 100 °C under nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with EA to afford tert-butyl 4-(8-fluoro-2-{8-fluoro-2- methylimidazo[1,2-a] pyridin-6-yl}quinolin-6-yl)piperazine-1-carboxylate (110 mg, 85%) as a solid. LCMS (ES, m/z): 480 [M+H] ⁺ . Synthesis of Compound 517 A mixture of tert-butyl 4-(8-fluoro-2-{8-fluoro-2-methylimidazo[1,2-a] pyridin-6-yl}quinolin-6- yl)piperazine-1-carboxylate (100 mg, 0.209 mmol, 1 equiv) and trifluoroacetic acid (0.5 mL ) in DCM (2 mL) was stirred for 2 h at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by reverse flash chromatography (Condition 9, Gradient 4) to afford 8-fluoro-2-{8-fluoro-2-methylimidazo[1,2- a]pyridin-6-yl}-6-(piperazin-1-yl)quinoline (40 mg, 51%) as a solid. LCMS (ES, m/z): 380 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d ₆ ) δ λ.25 (s, 1H), 8.28 (d, J = 8.λ Hz, 1H), 8.08 (d, J = 8.8 Hz, 1H), 7.92 (d, J = 12.9 Hz, 2H), 7.54 (d, J = 13.9 Hz, 1H), 7.04 (s, 1H), 3.24 (d, J = 6.0 Hz, 4H), 2.88 (s, 4H), 2.39 (s, 3H). Example 185: Synthesis of Compound 513 Synthesis of Intermediate C218 A mixture of 2,6-dichloro-4-(1-ethoxyethenyl)quinazoline (400 mg, 1.486 mmol, 1.0 equiv), 7- fluoro-6-(methoxymethoxy)-2-methyl-5-(4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl)indazole (499.64 mg, 1.486 mmol, 1.0 equiv), K3PO4 (473.22 mg, 2.229 mmol, 1.50 equiv), dioxane (1 mL), water (0.2 mL) and Pd(dppf)Cl ₂ (121.07 mg, 0.149 mmol, 0.1 equiv) was stirred overnight at 80 °C under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:3) to afford 6-chloro-4-(1-ethoxyethenyl)-2-[7-fluoro-6-(methoxymethoxy)- 2- methylindazol-5-yl]quinazoline (400 mg, 61%) as a solid. LCMS (ES, m/z): 443 [M+H] ⁺ . Synthesis of Intermediate C219 A mixture of 6-chloro-4-(1-ethoxyethenyl)-2-[7-fluoro-6-(methoxymethoxy)- 2-methylindazol-5- yl]quinazoline (200 mg, 0.452 mmol, 1.0 equiv), tert-butyl piperazine-1-carboxylate (126.17 mg, 0.678 mmol, 1.5 equiv), X-Phos (43.06 mg, 0.090 mmol, 0.2 equiv), dioxane (4 mL), Pd2(dba) ₃ (41.35 mg, 0.045 mmol, 0.1 equiv) and Cs ₂ CO ₃ (220.70 mg, 0.678 mmol, 1.5 equiv) was stirred overnight at 80 °C under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ / MeOH (20:1) to afford tert-butyl 4-[4-(1-ethoxyethenyl)- 2-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5-yl]quinazol in-6-yl]piperazine-1-carboxylate (210 mg, 78%) as a solid. LCMS (ES, m/z): 593 [M+H] ⁺ . Synthesis of Compound 513 A mixture of tert-butyl 4-[4-(1-ethoxyethenyl)-2-[7-fluoro-6-(methoxymethoxy)-2- methylindazol-5-yl]quinazolin-6-yl]piperazine-1-carboxylate (200 mg, 0.337 mmol, 1 equiv) and HCl (gas) in 1,4-dioxane (5 mL) was stirred for 4 h at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by reverse flash chromatography (Condition 4, Gradient 1) to afford 1-(2-(7-fluoro-6-hydroxy-2-methyl- 2H-indazol-5-yl)-6-(piperazin-1-yl)quinazolin-4-yl)ethan-1-o ne 2,2,2-trifluoroacetate (35 mg, 25%) as a solid. LCMS (ES, m/z): 421 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 13.21 (s, 1H), 8.91 (s, 1H), 8.83 (s, 2H), 8.59 (d, J = 2.6 Hz, 1H), 8.15 (d, J = 9.4 Hz, 1H), 8.06 (dd, J = 9.5, 2.8 Hz, 1H), 7.98 (d, J = 2.7 Hz, 1H), 4.19 (s, 3H), 3.59 (d, J = 5.5 Hz, 4H), 3.34 (d, J = 5.5 Hz, 4H), 2.93 (s, 3H). Example 186: Synthesis of Compound 663 Synthesis of Intermediate C220

To a stirred mixture of 2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]pyrido[3,2- d]pyrimidin-6-ol (350 mg, 0.996 mmol, 1 equiv) and tert-butyl (2R,6S)-2,6-dimethylpiperazine- 1-carboxylate (320 mg, 1.494 mmol, 1.5 equiv) in acetonitrile (10 mL) was added BOP (881 mg, 1.992 mmol, 2 equiv) and DBU (455 mg, 2.988 mmol, 3 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 24 h at 55 °C under nitrogen atmosphere, then cooled to room temperature, quenched with water (50 mL), and extracted with ethyl acetate (3 x 20 mL). The organic layers were combined, washed with brine (1 x 20 mL), dried over anhydrous Na ₂ SO4, and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with EA to afford tert-butyl (2R,6S)-4-[2-(6-hydroxy-2,7-dimethylindazol-5-yl)pyrido[3,2- d]pyrimidin-6- yl]-2,6-dimethylpiperazine-1-carboxylate (400 mg, 80%) as a solid. LCMS (ES, m/z): 548 [M+H] ⁺ . Synthesis of Compound 663 A mixture of tert-butyl (2R,6S)-4-{2-[6-(methoxymethoxy)-2,7-dimethylindazol-5- yl]pyrido[3,2-d]pyrimidin-6-yl}-2,6-dimethylpiperazine-1-car boxylate (168 mg, 0.307 mmol, 1 equiv) and 4 M HCl (gas) in 1,4-dioxane (1 mL) in DCM (3 mL) was stirred for 1 h at room temperature. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by reverse flash chromatography (Condition 10, Gradient 1) to afford 5-{6- [(3R,5S)-3,5-dimethylpiperazin-1-yl]pyrido[3,2-d]pyrimidin-2 -yl}-2,7-dimethylindazol-6-ol (75 mg, 61%) as a solid. LCMS (ES, m/z): 404 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d6) δ 13.2λ (s, 1H), 9.25 (s, 1H), 8.85 (s, 1H), 8.40 (s, 1H), 8.18 (d, J = 9.5 Hz, 1H), 7.81 (d, J = 9.6 Hz, 1H), 4.50 (d, J = 12.4 Hz, 2H), 4.14 (s, 3H), 2.77 (s, 2H), 2.43 (d, J = 23.9 Hz, 5H), 1.08 (d, J = 6.1 Hz, 6H). Example 187: Synthesis of Compound 544 Synthesis of Intermediate C221 To a stirred mixture of 6-bromo-8-fluoroquinolin-2-ol (500 mg, 2.066 mmol, 1 equiv), t-BuONa (595 mg, 6.198 mmol, 3 equiv), and tert-butyl (2R,6S)-2,6-dimethylpiperazine-1-carboxylate (664 mg, 3.099 mmol, 1.5 equiv) in dioxane (10 mL) was added 1,2,3,4,5-pentaphenyl-1'-(di- tert-butylphosphino)ferrocene (293 mg, 0.413 mmol, 0.2 equiv) and Pd ₂ (dba) ₃ (189 mg, 0.207 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 h at 100 °C under nitrogen atmosphere. The resulting mixture was concentrated under vacuum to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:8) to afford tert-butyl (2R,6S)-4-(8-fluoro-2-hydroxyquinolin-6-yl)-2,6- dimethylpiperazine-1-carboxylate (450 mg, 58%) as a solid. LCMS (ES, m/z): 376 [M+H] ⁺ . Synthesis of Intermediate C222 To a stirred mixture of tert-butyl (2R,6S)-4-(8-fluoro-2-hydroxyquinolin-6-yl)-2,6- dimethylpiperazine-1-carboxylate (460 mg, 1.225 mmol, 1 equiv) and PyBrOP (856 mg, 1.838 mmol, 1.5 equiv) in dioxane (5 mL) was added TEA (371mg, 3.675 mmol, 3 equiv) and K ₂ CO ₃ (508 mg, 3.675 mmol, 3 equiv) at room temperature. The resulting mixture was stirred for 3 h at 100 °C, then cooled to room temperature. To the reaction mixture were added water (0.3 mL), (8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)boronic acid (360 mg, 1.838 mmol, 1.5 equiv), and Pd(dppf)Cl ₂ (89 mg, 0.123 mmol, 0.1 equiv) at room temperature. The resulting mixture was stirred for 16 h at 100 °C under nitrogen atmosphere, then cooled to room temperature. The resulting mixture was filtered and the filter cake washed with ethyl acetate (3 x 40 mL). The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with EA/MeOH (10:1) to afford tert-butyl (2R,6S)-4- (8-fluoro-2-{8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl}qui nolin-6-yl)-2,6- dimethylpiperazine-1-carboxylate (300 mg, 48%) as a solid. LCMS (ES, m/z): 508 [M+H] ⁺ . Synthesis of Compound 544 A mixture of tert-butyl (2R,6S)-4-(8-fluoro-2-{8-fluoro-2-methylimidazo[1,2-a] pyridin-6- yl}quinolin-6-yl)-2,6-dimethylpiperazine-1-carboxylate (250 mg, 0.493 mmol, 1 equiv) and trifluoroacetic acid (1 mL) in DCM (5 mL) was stirred for 2 h at room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by reversed-phase flash chromatography (Condition 10, Gradient 10) to afford 6-[(3R,5S)-3,5- dimethylpiperazin-1-yl]-8-fluoro-2-{8-fluoro-2-methylimidazo [1,2-a]pyridin-6-yl}quinoline (105 mg, 52%) as a solid. LCMS (ES, m/z): 408 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 9.25 (d, J = 1.4 Hz, 1H), 8.28 (dd, J = 8.9, 1.7 Hz, 1H), 8.07 (d, J = 8.8 Hz, 1H), 7.97 -7.86 (m, 2H), 7.56 (dd, J = 14.6, 2.5 Hz, 1H), 7.07-7.00 (m, 1H), 3.77 (d, J = 11.4 Hz, 2H), 2.87 (s, 2H), 2.43-2.36 (m, 3H), 2.27 (t, J = 11.1 Hz, 3H), 1.07 (d, J = 6.2 Hz, 6H). Example 188: Synthesis of Compound 331 Synthesis of Intermediate C223 To a stirred mixture of 2-{8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl}pyrido[3,2-d] pyrimidin- 6-ol (240 mg, 0.813 mmol, 1 equiv) and tert-butyl N-methyl-N-[(3R)-pyrrolidin-3-yl]carbamate (244 mg, 1.220 mmol, 1.5 equiv) in acetonitrile (10 mL) was added BOP (719 mg, 1.626 mmol, 2 equiv) and DBU (248 mg, 1.626 mmol, 2 equiv) at room temperature. The resulting mixture was stirred for overnight at room temperature, then quenched with water (50 mL) and extracted with ethyl acetate (3 x 20 mL). The organic layers were combined, washed with brine (1 x 20 mL), dried over anhydrous Na ₂ SO ₄ , and filtered. The filtrate was concentrated under reduced pressure to give a residue. The residue was purified by reverse flash chromatography (Condition 7, Gradient 1) to afford tert-butyl N-[(3R)-1-(2-{8-fluoro-2-methylimidazo[1,2-a]pyridin-6- yl}pyrido[3,2-d]pyrimidin-6-yl)pyrrolidin-3-yl]-N-methylcarb amate (220 mg, 57%) as a solid. LCMS (ES, m/z): 478 [M+H] ⁺ . A mixture of tert-butyl N-[(3R)-1-(2-{8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl}py rido[3,2- d]pyrimidin-6-yl)pyrrolidin-3-yl]-N-methylcarbamate (220 mg, 0.461 mmol, 1 equiv) and 4 M HCl (gas) in 1,4-dioxane (1 mL) in DCM (3 mL) was stirred for 1 h at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by reverse flash chromatography (Condition 10, Gradient 11) to afford (3R)-1-(2-{8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl}pyrid o[3,2-d]pyrimidin-6- yl)-N-methylpyrrolidin-3-amine (120 mg, 69%) as a solid. LCMS (ES, m/z): 378 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d6) δ λ.3λ (d, J = 1.3 Hz, 1H), 9.19 (s, 1H), 8.09 (d, J = 9.3 Hz, 1H), 8.02 (d, J = 3.1 Hz, 1H), 7.92 (dd, J = 12.5, 1.4 Hz, 1H), 7.40 (d, J = 9.4 Hz, 1H), 3.74 (dd, J = 11.1, 5.9 Hz, 1H), 3.66 (d, J = 9.8 Hz, 2H), 3.47 (s, 2H), 2.38 (d, J = 8.2 Hz, 6H), 2.15 (dd, J = 12.7, 5.8 Hz, 1H), 1.92 (s, 1H). Example 189: Synthesis of Compound 506 Synthesis of Intermediate C224 To a mixture of ethyl 2,6-dichloroquinazoline-4-carboxylate (1.5 g, 5.533 mmol, 1.0 equiv) and 7-fluoro-6-(methoxymethoxy)-2-methyl-5-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)indazole (1.8 g, 5.533 mmol, 1.0 equiv) in dioxane (20 mL) and water (2 mL) was added K ₃ PO ₄ (2.3 g, 11.066 mmol, 2.0 equiv) and Pd(dppf)Cl ₂ (0.4 g, 0.553 mmol, 0.1 equiv). The reaction mixture was stirred for 3 h at 80 °C under a nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to afford ethyl 6-chloro-2-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5- yl]quinazoline-4-carboxylate (1.4 g, 52%) as a solid. LCMS (ES, m/z): 445 [M+H] ⁺ . Synthesis of Intermediate C225 To a mixture of ethyl 6-chloro-2-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5- yl]quinazoline-4- carboxylate (330.0 mg, 0.742 mmol, 1.0 equiv) and tert-butyl piperazine-1- carboxylate (179.6 mg, 0.965 mmol, 1.3 equiv) in dioxane (8 mL) was added Cs2CO ₃ (483.4 mg, 1.484 mmol, 2.0 equiv), Pd ₂ (dba) ₃ (67.9 mg, 0.074 mmol, 0.1 equiv), and XPhos (70.73 mg, 0.148 mmol, 0.2 equiv). The reaction mixture was stirred for 3 h at 80 °C under a nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to afford ethyl 6-[4-(tert- butoxycarbonyl)piperazin-1-yl]-2-[7-fluoro-6-(methoxymethoxy )-2-methylindazol-5- yl]quinazoline-4-carboxylate (320 mg, 65%) as a solid. LCMS (ES, m/z): 595 [M+H] ⁺ . A mixture of ethyl 6-[4-(tert-butoxycarbonyl)piperazin-1-yl]-2-[7-fluoro-6-(met hoxymethoxy) - 2-methylindazol-5-yl]quinazoline-4-carboxylate (300.0 mg, 0.505 mmol, 1.0 equiv) and CH ₃ NH ₂ in methanol (5 mL, 2M) was stirred for 5 h at 80 °C. The resulting mixture was concentrated under reduced pressure to afford tert-butyl 4-{2-[7-fluoro-6-(methoxymethoxy)-2- methylindazol-5-yl]-4-(methylcarbamoyl)quinazolin-6-yl} piperazine-1-carboxylate (300 mg, 87%) as a solid. LCMS (ES, m/z): 580 [M+H] ⁺ . Synthesis of Compound 506 To a stirred solution of tert-butyl 4-{2-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5-yl]-4 - (methylcarbamoyl)quinazolin-6-yl}piperazine-1-carboxylate (150.0 mg, 0.259 mmol, 1.0 equiv) in DCM (2 mL) was added TFA (0.3 mL) dropwise at room temperature. The resulting mixture was stirred for 1 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 8, Gradient 1) to afford 2-(7-fluoro- 6-hydroxy-2-methylindazol-5-yl) -N-methyl-6-(piperazin-1-yl)quinazoline-4-carboxamide (40 mg, 35%) as a solid. LCMS (ES, m/z): 436 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.36 (s, 1H), 9.28 (d, J = 5.1 Hz, 1H), 9.14 (s, 2H), 9.08 (s, 1H), 8.59 (d, J = 2.6 Hz, 1H), 8.26 (d, J = 2.7 Hz, 1H), 8.12 (d, J = 9.3 Hz, 1H), 8.04 (dd, J = 9.4, 2.8 Hz, 1H), 4.20 (s, 3H), 3.63-3.56 (m, 4H), 3.32-3.31 (m, 4H), 2.97 (d, J = 4.4 Hz, 3H). Example 190: Synthesis of Compound 667 Synthesis of Intermediate C227 To a mixture of ethyl 6-chloro-2-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5- yl]quinazoline-4 –carboxylate (330.0 mg, 0.742 mmol, 1.0 equiv) and tert-butyl (2R,6S)-2,6- dimethylpiperazine-1-carboxylate (206.6 mg, 0.965 mmol, 1.3 equiv) in dioxane (8 mL) was added Cs ₂ CO ₃ (483.4 mg, 1.484 mmol, 2.0 equiv), Pd ₂ (dba) ₃ (67.9 mg, 0.074 mmol, 0.1 equiv), and XPhos (70.7 mg, 0.148 mmol, 0.2 equiv). The reaction mixture was stirred for 3 h at 80 °C under a nitrogen atmosphere, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to afford ethyl 6-[(3R,5S)-4-(tert-butoxycarbonyl)-3,5-dimethylpiperazin-1-y l]-2-[7-fluoro-6- (methoxymethoxy)-2-methylindazol-5-yl]quinazoline-4-carboxyl ate (350 mg, 69%) as a solid. LCMS (ES, m/z): 623 [M+H] ⁺ . Synthesis of Intermediate C228

A mixture of ethyl 6-[(3R,5S)-4-(tert-butoxycarbonyl)-3,5-dimethylpiperazin-1-y l]-2-[7- fluoro- 6-(methoxymethoxy)-2-methylindazol-5-yl]quinazoline-4-carbox ylate (330.0 mg, 0.530 mmol, 1.0 equiv) and methylamine (2M in methanol) (5 mL) was stirred for 5 h at 80°C. The resulting mixture was concentrated under reduced pressure to afford tert-butyl (2R,6S)-4-{2-[7-fluoro-6- (methoxymethoxy)-2-methylindazol-5-yl]-4-(methylcarbamoyl)qu inazolin-6-yl}-2,6- dimethylpiperazine-1-carboxylate (320 mg, 84%) as a solid. LCMS (ES, m/z): 608 [M+H] ⁺ . To a stirred solution of tert-butyl (2R,6S)-4-{2-[7-fluoro-6-(methoxymethoxy)-2-methylindazol- 5-yl]-4- (methylcarbamoyl)quinazolin-6-yl}-2,6-dimethylpiperazine-1-c arboxylate (150.0 mg, 0.247 mmol, 1.0 equiv) in DCM (2 mL) was added TFA (0.5 mL) dropwise at room temperature. The resulting mixture was stirred for 1 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by Prep-HPLC (Condition 15, Gradient 1) to afford 6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-2-(7-fluoro-6-hydroxy -2-methylindazol-5-yl)-N- methylquinazoline-4-carboxamide (53 mg, 46%) as a solid. LCMS (ES, m/z): 464 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6) δ 13.42 (s, 1H), λ.23 (d, J = 5.1 Hz, 1H), 9.04 (d, J = 0.9 Hz, 1H), 8.57 (d, J = 2.5 Hz, 1H), 8.17 (t, J = 1.7 Hz, 1H), 8.01 (d, J = 1.6 Hz, 2H), 4.19 (s, 3H), 3.77 (dd, J = 11.9, 2.8 Hz, 2H), 2.97 (d, J = 4.6 Hz, 3H), 2.90 (ddd, J = 9.8, 6.1, 2.9 Hz, 2H), 2.34 (t, J = 11.1 Hz, 2H), 1.09 (d, J = 6.3 Hz, 6H). Example 191: Synthesis of Compound 528 Synthesis of Intermediate C229 To a stirred mixture of ethyl 6-chloro-2-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5- yl]quinazoline-4-carboxylate (300 mg, 0.674 mmol, 1 equiv) and N,N-dimethylpiperidin-4- amine (103 mg, 0.809 mmol, 1.2 equiv) in 1,4-dioxane (3 mL) was added Cs ₂ CO ₃ (659 mg, 2.022 mmol, 3 equiv), RuPhos (62 mg, 0.135 mmol, 0.2 equiv), and Pd2(dba) ₃ (61 mg, 0.067 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 h at 100 °C, then cooled to room temperature. The resulting mixture was concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford ethyl 6-[4- (dimethylamino)piperidin-1-yl]-2-[7-fluoro-6-(methoxymethoxy )-2-methylindazol-5- yl]quinazoline-4-carboxylate (300 mg, 83%) as a solid. LCMS (ES, m/z): 537 [M+H] ⁺ . A mixture of ethyl 6-[4-(dimethylamino)piperidin-1-yl]-2-[7-fluoro-6-(methoxyme thoxy)-2- methylindazol-5-yl]quinazoline-4-carboxylate (300 mg, 0.559 mmol, 1 equiv) and MeNH ₂ solution in methanol (5 mL) was stirred for 16 h at 80 °C. The mixture was cooled to room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 6-[4- (dimethylamino)piperidin-1-yl]-2-[7-fluoro-6-(methoxymethoxy )-2-methylindazol-5-yl]-N- methylquinazoline-4-carboxamide (250 mg, 86%) as a solid. LCMS (ES, m/z): 522 [M+H] ⁺ . To a stirred solution of 6-[4-(dimethylamino)piperidin-1-yl]-2-[7-fluoro-6-(methoxyme thoxy)-2- methylindazol-5-yl]-N-methylquinazoline-4-carboxamide (250 mg, 0.479 mmol, 1 equiv) in DCM (3 mL) was added TFA (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by reverse flash chromatography (Condition 10, Gradient 10) to afford 6-[4- (dimethylamino)piperidin-1-yl]-2-(7-fluoro-6-hydroxy-2-methy lindazol-5-yl)-N- methylquinazoline-4-carboxamide (50 mg, 22%) as a solid. LCMS (ES, m/z): 478 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d6) δ 13.43 (s, 1H), λ.22 (d, J = 5.0 Hz, 1H), 9.04 (d, J = 1.0 Hz, 1H), 8.57 (d, J = 2.6 Hz, 1H), 8.17 (d, J = 1.7 Hz, 1H), 8.00 (d, J = 1.5 Hz, 2H), 4.19 (s, 3H), 3.94 (d, J = 12.6 Hz, 2H), 3.00-2.85 (m, 5H), 2.33 (s, 1H), 2.22 (s, 6H), 1.96-1.86 (m, 2H), 1.51 (q, J = 10.8 Hz, 2H). Example 192: Synthesis of Compound 529 Synthesis of Intermediate C231 To a stirred mixture of ethyl 6-chloro-2-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5- yl]quinazoline-4-carboxylate (320 mg, 0.719 mmol, 1 equiv) and tert-butyl (2S)-2- methylpiperazine-1-carboxylate (172 mg, 0.863 mmol, 1.2 equiv) in 1,4-dioxane (3 mL) was added Cs ₂ CO ₃ (703 mg, 2.157 mmol, 3 equiv), RuPhos (67 mg, 0.144 mmol, 0.2 equiv), and Pd2(dba) ₃ (65 mg, 0.072 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 h at 100°C, then cooled to room temperature and concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford ethyl 6-[(3S)-4-(tert-butoxycarbonyl)-3- methylpiperazin-1-yl]-2-[7-fluoro-6-(methoxymethoxy)-2-methy lindazol-5-yl]quinazoline-4- carboxylate (340 mg, 78%) as a solid. LCMS (ES, m/z): 609 [M+H] ⁺ . A mixture of ethyl 6-[(3S)-4-(tert-butoxycarbonyl)-3-methylpiperazin-1-yl]-2-[7 -fluoro-6- (methoxymethoxy)-2-methylindazol-5-yl]quinazoline-4-carboxyl ate (300 mg, 0.493 mmol, 1 equiv) and MeNH ₂ in methanol (3 mL) was stirred for overnight at 80 °C. The reaction mixture was cooled to room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford tert-butyl (2S)-4-{2-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5-yl] -4- (methylcarbamoyl)quinazolin-6-yl}-2-methylpiperazine-1-carbo xylate (260 mg, 89%) as a solid. LCMS (ES, m/z): 594 [M+H] ⁺ . Synthesis of Compound 529

To a stirred solution of tert-butyl (2S)-4-{2-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5- yl]-4-(methylcarbamoyl)quinazolin-6-yl}-2-methylpiperazine-1 -carboxylate (260 mg, 0.438 mmol, 1 equiv) in DCM (3 mL) was added TFA (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature, then concentrated under reduced pressure to give a residue. The residue was purified by reverse flash chromatography (Condition 10, Gradient 10) to afford 2-(7-fluoro-6-hydroxy-2-methylindazol-5-yl)-N-methyl-6-[(3S) -3- methylpiperazin-1-yl]quinazoline-4-carboxamide (60 mg, 30%) as a solid. LCMS (ES, m/z): 450 [M+H] ⁺ . ¹ H NMR (300 MHz, DMSO-d6) δ 13.44 (s, 1H), λ.23 (d, J = 5.2 Hz, 1H), 9.05 (d, J = 1.1 Hz, 1H), 8.58 (d, J = 2.7 Hz, 1H), 8.16 (s, 1H), 8.02 (s, 2H), 4.19 (s, 3H), 3.78 (d, J = 10.1 Hz, 2H), 3.05 (d, J = 10.6 Hz, 1H), 2.97 (d, J = 4.7 Hz, 3H), 2.80 (t, J = 12.1 Hz, 3H), 2.42 (t, J = 10.7 Hz, 1H), 1.09 (d, J = 6.2 Hz, 3H) ^. Example 193: Synthesis of Compound 385 Into a 20mL vial were added 2-chloro-6-[6-(methoxymethoxy)-2-methylindazol-5-yl]-1,5- naphthyridine (150 mg, 0.423 mmol, 1 equiv), tert-butyl N-cyclopropyl-N-(pyrrolidin-3- yl)carbamate (114.82 mg, 0.508 mmol, 1.2 equiv), DMSO (4 mL, 56.314 mmol, 133.20 equiv) and DIEA (163.93 mg, 1.269 mmol, 3 equiv) at room temperature. The resulting mixture was stirred for overnight at 100°C. The mixture was allowed to cool down to room temperature. The reaction was quenched by the addition of Water (10 mL) at room temperature. The resulting mixture was extracted with EtOAc (3 x 5 mL). The combined organic layers were washed with subsaturation brine (3x5 mL), dried over anhydrous Na ₂ SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with CH ₂ Cl ₂ /EA (1:4) to afford tert-butyl N-cyclopropyl-N-(1-{6-[6- (methoxymethoxy)-2-methylindazol -5-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl)carbamate (130 mg, 56.45%) as a Brown yellow oil. LCMS (ES, m/z): 545 [M+H] + Example 194: Synthesis of Compound 386 Synthesis of Intermediate D2 To a stirred mixture of 2,6-dichloro-1,5-naphthyridine (D1, 1 g, 5.024 mmol, 1 equiv) and tert- butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro- 2H-pyridine-1-carboxylate (1.55 g, 5.024 mmol, 1 equiv) and Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (0.28 g, 0.502 mmol, 0.1 equiv) in 1,4- dioxane (20 mL) was added K3PO4 (3.20 g, 15.072 mmol, 3 equiv) in water (4 mL) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 80 °C under nitrogen atmosphere. The mixture was allowed to cool to room temperature, then diluted with water (60 mL) and extracted with EtOAc (3 x 60 mL). The combined organic layers were washed with brine (1x50 mL) and subsequently dried over anhydrous Na ₂ SO4. After filtration, the filtrate was concentrated under reduced pressure and purified by silica gel column chromatography and eluted with CH ₂ Cl ₂ / EtOAc (1:1) to afford tert-butyl 4-(6-chloro-1,5- naphthyridin-2-yl)-3,6-dihydro-2H-pyridine -1-carboxylate (D2, 800 mg). LCMS: (ESI, m/z): 346[M+H]. Synthesis of Intermediate D3 A mixture of CuCl (34.35 mg, 0.347 mmol, 0.3 equiv) and (2S,4S)-(-)-2,4- Bis(diphenylphosphino)pentane (101.90 mg, 0.231 mmol, 0.2 equiv) and sodium 2- methylpropan-2-olate (222.31 mg, 2.314 mmol, 2 equiv) and sodium tetrakis[3,5- bis(trifluoromethyl)phenyl]borate (205 mg, 0.231 mmol, 0.2 equiv) in THF (15 mL) was stirred for 10 min at room temperature under nitrogen atmosphere. To the above mixture was added 4,4,5,5-tetramethyl-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)- 1,3,2-dioxaborolane (881.15 mg, 3.471 mmol, 3 equiv) (in 7.5 mL THF) dropwise over 10 min at 0 °C. The resulting mixture was stirred for additional 10 min at room temperature. To the above mixture was added Intermediate D2 (400 mg, 1.157 mmol, 1 equiv) in THF(7.5 mL)/MeOH(10 mL)) dropwise over 15 min at 0 °C. The resulting mixture was stirred for an additional 3 days at room temperature, quenched by the addition of water/ice (50 mL) at 0 °C and extracted with CH ₂ Cl ₂ (3 x 50 mL). The combined organic layers were washed with brine (1x50 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was subsequently purified by reverse flash chromatography, Condition 3, Gradient 6 as previously described to afford (3S)-4-(6-chloro-1,5- naphthyridin-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan -2-yl) piperidine-1- carboxylate (D3, 200 mg). LCMS: (ESI, m/z): 474[M+H]. Synthesis of Intermediate D4 To a stirred mixture of Intermediate D3 (200 mg, 0.422 mmol, 1 equiv) in THF (4 mL) was added NaOH (3M, aq) (4 mL) was added dropwise to a stirred mixture of Intermediate D3 (200 mg, 0.422 mmol, 1 equiv) in THF (4 mL) at 0 °C. To the above mixture was added H ₂ O ₂ (30%) (2 mL) dropwise at 0 °C, and the resulting mixture was stirred for an additional 1.5 h at room temperature. The reaction was quenched by the addition of sat. Na ₂ S ₂ O ₃ (aq.) (20 mL) at 0 °C and subsequently extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine (1x30 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by reverse flash chromatography following Condition 3, Gradient 7 as previously described. Further, the residue was purified by silica gel column chromatography and eluted with DCE / EA (2:1) to afford tert-butyl (3S)-4-(6-chloro-1,5- naphthyridin-2-yl)-3-hydroxypiperidine-1-carboxylate (D4, 75 mg). LCMS: (ESI, m/z): 364[M+H]. Synthesis of Intermediate D5 A mixture of Intermediate D4 (65.59 mg, 0.206 mmol, 1 equiv), Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (11.39 mg, 0.021 mmol, 0.1 equiv) and K ₃ PO ₄ (131.27 mg, 0.618 mmol, 3 equiv) in 1,4-dioxane (1.5 mL) /water (0.5 mL) was stirred for 2 h at 80 °C under nitrogen atmosphere and later allowed to cool to room temperature. The resulting mixture was diluted with water (10 mL) and extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (1x10 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with DCM / EA (1:1) to afford tert- butyl (3S)-3-hydroxy-4-{6-[6-(methoxymethoxy)-2-methylindazol-5-yl ]-1,5-naphthyridin-2- yl}piperidine-1-carboxylate (D5, 50 mg). LCMS: (ESI, m/z): 520[M+H]. Synthesis of Compound 386 To a stirred mixture of Intermediate D5 (50 mg, 0.096 mmol, 1 equiv) in MeOH (2.5 mL) was added HCl(gas)in 1,4-dioxane (2.5 mL) dropwise at room temperature under air atmosphere. The resulting mixture was stirred for 4 h at room temperature under air atmosphere and later concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 2, Gradient 1 as previously described to afford 5-{6-[(3S)-3-hydroxypiperidin-4-yl]- 1,5-naphthyridin-2-yl}-2-methylindazol-6-ol (Compound 386, 10.7 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ESI, m/z): 376[M+H]. ¹ H NMR: (400 MHz, DMSO-d ₆ )μ δ 13.65 (s, 1H), 8.70 (s, 1H), 8.61 (d, J = 9.3 Hz, 1H), 8.49 (d, J = 9.1 Hz, 1H), 8.41 (d, J = 7.4 Hz, 2H), 7.81 (d, J = 8.8 Hz, 1H), 6.92 (s, 1H), 4.72 (d, J = 5.2 Hz, 1H), 4.13 (s, 4H), 3.18 (dt, J = 12.6, 3.1 Hz, 1H), 3.10 (d, J = 13.3 Hz, 1H), 2.97 (dd, J = 13.4, 2.8 Hz, 1H), 2.82 (dd, J = 13.2, 1.7 Hz, 1H), 2.63 (dd, J = 12.7, 2.8 Hz, 1H), 2.20 (qd, J = 12.6, 4.2 Hz, 1H), 1.70 (d, J = 12.6 Hz, 1H). Example 195: Synthesis of Compound 387 Synthesis of Intermediate D7 A solution of tert-butyl N-[1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3-yl]-N- (cyclopropylmethyl)carbamate (D6, 500 mg, 1.241 mmol, 1 equiv), 7-fluoro-6-methoxy-2- methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazo le (380 mg, 1.241 mmol, 1 equiv), Pd(DtBPF)Cl ₂ (81 mg, 0.124 mmol, 0.1 equiv) and K ₃ PO ₄ (790 mg, 3.723 mmol, 3 equiv) in dioxane (10 mL) and H ₂ O (2 mL) was stirred for 16 h at 80 °C under nitrogen atmosphere and was subsequently allowed to cool to room temperature. The resulting mixture was poured into water (20 mL), extracted with EA (3 x 20 mL) and dried over anhydrous Na ₂ SO ₄ . After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford tert-butyl N- (cyclopropylmethyl)-N-{1-[6-(7-fluoro-6-methoxy-2-methylinda zol-5-yl)-1,5-naphthyridin-2- yl]pyrrolidin-3-yl}carbamate (D7, 300 mg). LCMS: (ES, m/z):547 [M+H] ⁺ Synthesis of Intermediate D8 To a stirred solution of Intermediate D7 (300 mg, 0.549 mmol, 1 equiv) in DCM (6 mL) was added BBr3 (687 mg, 2.745 mmol, 5 equiv) dropwise at 0 °C, and the resulting mixture was stirred for 16 h at room temperature. The reaction was quenched by the addition of MeOH (30 mL) at 0 °C and concentrated under reduced pressure. The mixture was then basified to pH 8 with saturated NaHCO ₃ (aq.), extracted with CH ₂ Cl ₂ (3 x 50 mL) and dried over anhydrous Na ₂ SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by Chiral-Prep-HPLC following Condition 9, Gradient 1 as previously described to afford 5-(6-{3-[(cyclopropylmethyl)amino]pyrrolidin-1-yl}-1,5-napht hyridin-2-yl)-7-fluoro-2- methylindazol-6-ol (75 mg) as a yellow solid.5-(6-{3-[(cyclopropylmethyl)amino]pyrrolidin-1- yl}-1,5-naphthyridin-2-yl)-7-fluoro-2-methylindazol-6-ol (D8, 13.2 mg) to QC. LCMS: (ES, m/z):433 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 14.44 (s, 1H), 8.48 (d, J = 2.7 Hz, 1H), 8.44 – 8.37 (m, 2H), 8.14 (dd, J = 9.3, 0.8 Hz, 1H), 8.11 – 8.05 (m, 1H), 7.17 (d, J = 9.3 Hz, 1H), 4.16 (s, 3H), 3.82 – 3.68 (m, 3H), 3.57 (d, J = 8.8 Hz, 1H), 3.45 (t, J = 5.4 Hz, 1H), 2.46 (d, J = 6.6 Hz, 2H), 2.13 (dq, J = 12.9, 6.6 Hz, 1H), 1.88 (dd, J = 12.3, 6.2 Hz, 2H), 0.96 – 0.82 (m, 1H), 0.46 – 0.35 (m, 2H), 0.17 – 0.05 (m, 2H). Example 196: Synthesis of Compound 390 Synthesis of Intermediate D8 A solution of Intermediate D6 (500 mg, 1.241 mmol, 1 equiv), 5-methoxy-2,4-dimethyl-6- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol e (376 mg, 1.241 mmol, 1 equiv), Pd(DtBPF)Cl ₂ (81 mg, 0.124 mmol, 0.1 equiv) and K3PO4 (790 mg, 3.723 mmol, 3 equiv) in dioxane (10 mL) and H ₂ O (2 mL) was stirred for 16 h at 80 °C under nitrogen atmosphere and later allowed to cool to room temperature. The resulting mixture was poured into water (20 mL), extracted with EA (3 x 20 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford tert-butyl N-(cyclopropylmethyl)-N-{1-[6-(5-methoxy-2,4- dimethyl-1,3-benzoxazol-6-yl)-1,5-naphthyridin-2-yl]pyrrolid in-3-yl}carbamate (Intermediate D8, 360 mg). LCMS: (ES, m/z):544 [M+H] ⁺ . To a stirred solution of Intermediate D8 (360 mg, 0.662 mmol, 1 equiv) in DCM (7.2 mL) was added BBr ₃ (829 mg, 3.310 mmol, 5.00 equiv) dropwise at 0 °C, and the resulting mixture was stirred for 16 h at room temperature. The reaction was quenched by the addition of MeOH (30 mL) at 0 °C and concentrated under reduced pressure. The mixture was then basified to pH 8 with saturated NaHCO ₃ (aq.), extracted with CH ₂ Cl ₂ (3 x 50 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The crude product was purified by Chiral-Prep-HPLC following Condition 9, Gradient 1 as previously described to afford 6-(6-{3- [(cyclopropylmethyl)amino]pyrrolidin-1-yl}-1,5-naphthyridin- 2-yl)-2,4-dimethyl-1,3- benzoxazol-5-ol (140 mg).6-(6-{3-[(cyclopropylmethyl)amino]pyrrolidin-1-yl}-1,5- naphthyridin-2-yl)-2,4-dimethyl-1,3-benzoxazol-5-ol (Compound 390, 14.7 mg) to QC. LCMS: (ES, m/z):430 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 14.λλ (s, 1H), 8.41 (d, J = 9.3 Hz, 1H), 8.25 (s, 1H), 8.14 (dd, J = 9.2, 0.8 Hz, 1H), 8.07 (dd, J = 9.1, 0.8 Hz, 1H), 7.16 (d, J = 9.3 Hz, 1H), 3.74 (dd, J = 10.5, 5.8 Hz, 1H), 3.68 (s, 1H), 3.60 – 3.51 (m, 1H), 3.45 (t, J = 5.4 Hz, 1H), 3.41 – 3.30 (s, 1H), 2.61 (s, 3H), 2.46 (d, J = 6.8 Hz, 2H), 2.40 (s, 3H), 2.13 (dq, J = 12.9, 6.5 Hz, 1H), 1.87 (dd, J = 12.4, 6.4 Hz, 1H), 0.95 – 0.84 (m, 1H), 0.46 – 0.33 (m, 2H), 0.17 – 0.09 (m, 2H). Example 197: Synthesis of Compound 287 Synthesis of Intermediate D10 A mixture of 5-bromo-7-fluoro-6-(methoxymethoxy)-2-methylindazole (296.45 mg, 1.026 mmol, 1.2 equiv) and Pd(DtBPF)Cl ₂ (55.69 mg, 0.086 mmol, 0.1 equiv) in 1,4-dioxane (8 mL) was stirred for 45 min at 100 °C under nitrogen atmosphere. To the above mixture was added tert-butyl N-cyclopropyl-N-{1-[6- (trimethylstannyl)-1,5-naphthyridin -2-yl]pyrrolidin-3- yl}carbamate (D9, 680 mg, 0.855 mmol, 1 equiv, 65%) (in 1,4-dioxane (5.6 mL)) dropwise over 10 min at 100 °C, and the resulting mixture was stirred for additional 2 h at 100 °C and then allowed to cool down to room temperature. The resulting mixture was concentrated under reduced pressure, purified by silica gel column chromatography, and eluted with CH ₂ Cl ₂ / MeOH (10:1) to afford tert-butyl N-cyclopropyl-N-(1-{6-[7-fluoro- 6-(methoxymethoxy)-2- methylindazol -5-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl)carbamate (525mg). The crude product (525 mg) was purified by reverse flash chromatography following Condition 3, Gradient 3 as previously described, resulting in tert-butyl N-cyclopropyl-N-(1-{6-[7-fluoro-6- (methoxymethoxy)-2-methylindazol -5-yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl)carbamate (170 mg) and tert-butyl N-cyclopropyl-N- (1-{6-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5- yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-yl)carbamate (125 mg). The crude product (125 mg) was purified by Prep-HPLC following Condition 1, Gradient 32 as previously described to afford tert-butyl N-cyclopropyl-N-(1-{6-[7-fluoro-6-(methoxymethoxy)-2-methyli ndazol-5-yl]-1,5- naphthyridin-2- yl}pyrrolidin-3-yl)carbamate (D10, 75 mg). LCMS: (ESI, m/z): 563[M+H]. Synthesis of Compound 287 To a stirred solution of Intermediate D10 (245 mg, 0.435 mmol, 1 equiv) in DCM (12 mL) was added TFA (1.2 mL) dropwise at 0 °C, and the resulting mixture was subsequently stirred for 3 h at room temperature and later concentrated under vacuum. The crude product was purified by Prep-HPLC following Condition 1, Gradient 32 as previously described to afford 5-{6-[3- (cyclopropylamino)pyrrolidin-1-yl] -1,5-naphthyridin-2-yl}-7-fluoro-2-methylindazol-6-ol; trifluoroacetic acid (Compound 287, 170 mg) LCMS: (ESI, m/z): 419[M+H-TFA]. ¹ H-NMR: (400 MHz, DMSO-d6)μ δ 14.44 (s, 1H), 8.48 (d, J = 2.6 Hz, 1H), 8.43 – 8.36 (m, 2H), 8.13 (d, J = 9.3 Hz, 1H), 8.07 (d, J = 9.1 Hz, 1H), 7.15 (d, J = 9.3 Hz, 1H), 4.16 (s, 3H), 3.76 (dd, J = 10.9, 5.9 Hz, 1H), 3.67 (s, 1H), 3.57 (t, J = 5.6 Hz, 2H), 3.45 (s, 1H), 2.26 – 2.11 (m, 2H), δ 2.04 – 1.88 (m, 1H), 0.53 – 0.40 (m, 2H), 0.33 (q, J = 6.7, 4.2 Hz, 2H). Example 198: Synthesis of Compound 305 and Compound 306 The racemic Compound 287 (157.5 mg, 0.296 mmol, 1 equiv) was dissolved in DCM (5 mL), basified to pH 7 with NH ₃ (7 M) in MeOH, diluted with water (30 mL), and extracted with CH ₂ Cl ₂ (3 x 30 mL). The combined organic layers were washed with water (1x10 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. This resulted in the solid racemate (Compound 287, 126 mg). The racemate (126 mg) was purified by Chiral- Prep-HPLC following Condition 4, Gradient 10 as previously described. The product was dissolved in hexane (5 mL), and the precipitated solids were collected by filtration and washed with hexane (3x1 mL), resulting in resolution of the diastereomers. The stereochemistry was assigned arbitrarily. This resulted in 5-{6-[(3R)-3-(cyclopropylamino)pyrrolidin-1-yl]-1,5- naphthyridin-2-yl}-7-fluoro-2-methylindazol-6-ol (Compound 305, 35.4 mg). Compound 305 was resolved in the second peak. LCMS: (ESI, m/z): 419[M+H]. ¹ H-NMR: (400 MHz, DMSO- d6)μ δ 14.44 (s, 1H), 8.48 (d, J = 2.7 Hz, 1H), 8.44 – 8.37 (m, 2H), 8.11 (dd, J = 21.4, 9.2 Hz, 2H), 7.17 (d, J = 9.3 Hz, 1H), 4.16 (s, 3H), 3.75 (dd, J = 10.9, 5.8 Hz, 1H), 3.67 (s, 1H), 3.62 – 3.48 (m, 2H), 3.43 (s, 1H), 2.18 – 2.10 (m, 2H), 1.94 (s, 1H), 0.43 (d, J = 6.7 Hz, 2H), 0.30 – 0.21 (m, 2H). Compound 306, its diastereomer was resolved in the first peak.5-{6-[(3S)-3- (cyclopropylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2-yl}-7- fluoro-2-methylindazol-6-ol (Compound 306, 39.7 mg). LCMS: (ESI, m/z): 419[M+H]. ¹ H-NMR: (400 MHz, DMSO-d ₆ )μ δ 14.45 (s, 1H), 8.48 (d, J = 2.7 Hz, 1H), 8.40 (t, J = 4.6 Hz, 2H), 8.10 (dd, J = 20.8, 9.2 Hz, 2H), 7.16 (d, J = 9.3 Hz, 1H), 4.16 (s, 3H), 3.75 (dd, J = 10.8, 5.9 Hz, 1H), 3.70 – 3.62 (m, 1H), 3.61 – 3.47 (m, 2H), 3.42 (s, 1H), 2.15 (tt, J = 6.6, 3.3 Hz, 2H), 1.98 – 1.90 (m, 1H), 0.42 (t, J = 6.7 Hz, 2H), 0.34 – 0.21 (m, J = 5.7 Hz, 2H). Example 199: Synthesis of Compound 288 Synthesis of Intermediate D12 A solution of 5-bromo-6-(methoxymethoxy)-2,7-dimethylindazole (225 mg, 0.789 mmol, 1 equiv) and tert-butyl N-cyclobutyl-N-{1-[6-(trimethylstannyl)-1,5-naphthyridin-2-y l]pyrrolidin- 3-yl}carbamate (D11, 629 mg, 1.183 mmol, 1.5 equiv), Pd(DtBPF)Cl ₂ (51 mg, 0.079 mmol, 0.1 equiv) in 1,4-dioxane (2.25 mL) was stirred for 2h at 100°C under nitrogen atmosphe and later allowed to cool to room temperature. The resulting mixture was extracted with EA (1 x 10mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford tert-butyl N-cyclobutyl-N-(1-{6-[6-(methoxymethoxy) -2,7-dimethylindazol-5-yl]-1,5- naphthyridin-2-yl}pyrrolidin-3-yl)carbamate (D12, 149 mg). LCMS: (ES, m/z): 573 [M+H] ⁺ . A solution of Intermediate D12 (149 mg, 0.260 mmol, 1 equiv) in DCM (2 mL) and CF ₃ COOH (1 mL) was stirred for 1h at room temperature and subsequently concentrated under reduced pressure. The crude product was then purified by Prep-HPLC following Condition 1, Gradient 33 as previously described to afford 5-{6-[3-(cyclobutylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2 - yl}-2,7-dimethylindazol-6-ol (Compound 288, 8.4 mg). LCMS: (ES, m/z): 429 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d6) δ 14.33 (s, 1H), 8.43 – 8.36 (m, 2H), 8.33 (s, 1H), 8.06 (d, J = 9.1 Hz, 2H), 7.14 (d, J = 9.3 Hz, 1H), 4.13 (s, 3H), 3.69 (s, 2H), 3.68 (s, 1H), 3.55 (s, 1H), 3.25 (s, 2H), 2.38 (s, 3H), 2.14 (s, 4H), 2.18 – 2.05 (m, 1H), 1.82 (s, 2H), 1.75 – 1.50 (m, 2H). Example 200: Synthesis of Compound 289 The crude product 288 was purified by preparative chiral HPLC following Condition 10, Gradient 1 as previously described to afford the resolved diastereomers. Stereochemistry was assigned arbitrarily.5-{6-[(3R)-3-(cyclobutylamino)pyrrolidin-1-yl]-1 ,5-naphthyridin-2-yl} -2,7- dimethylindazol-6-ol (Compound 289, 22.3 mg). LCMS: (ES, m/z): 429 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 14.32 (s, 1H), 8.43 – 8.36 (m, 2H), 8.33 (s, 1H), 8.12 (d, J = 9.3 Hz, 1H), 8.06 (d, J = 9.1 Hz, 1H), 7.14 (d, J = 9.2 Hz, 1H), 4.13 (s, 3H), 3.69 (s, 2H), 3.55 (s, 1H), 3.38 (s, 2H), 3.23 (s, 1H),2.38 (s, 3H), 2.14 (s, 4H), 1.83 (s, 1H), 1.71 (s, 2H), 1.57 (dt, J = 18.3, 8.8 Hz, 2H).5-{6-[(3S)-3-(cyclobutylamino)pyrrolidin-1-yl]-1,5-napht hyridin-2-yl}-2,7- dimethylindazol-6-ol (Compound 290, 23.3 mg). LCMS: (ES, m/z): 429 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d6) δ 14.32 (s, 1H), 8.43 – 8.36 (m, 2H), 8.33 (s, 1H), 8.13 (d, J = 9.2 Hz, 1H), 8.06 (d, J = 9.1 Hz, 1H), 7.15 (d, J = 9.3 Hz, 1H), 4.13 (s, 3H), 3.70 (d, J = 7.8 Hz, 2H), 3.55 (d, J = 8.4 Hz, 1H), 3.38 (s, 2H), 3.23 (s, 1H),2.38 (s, 3H), 2.13 (s, 4H), 1.84 (s, 1H), 1.72 (s, 2H), 1.58 (dt, J = 18.7, 9.0 Hz, 2H). Example 201: Synthesis of Compounds 291 and 292 Synthesis of Intermediate D14 A solution of tert-butyl N-[1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3-yl]-N- (cyclopropylmethyl)carbamate (D13, 500 mg, 1.241 mmol, 1 equiv), 5-(methoxymethoxy)-2- methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-b enzoxazole (396 mg, 1.241 mmol, 1.00 equiv), Pd(DtBPF)Cl ₂ (81 mg, 0.124 mmol, 0.1 equiv) and K ₃ PO ₄ (790 mg, 3.723 mmol, 3 equiv) in dioxane (10 mL) and H ₂ O (2 mL) was stirred for 16 h at 80 °C under nitrogen atmosphere, and later allowed to cool to room temperature. The resulting mixture was poured into water (20 mL), extracted with EA (3 x 20 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford tert-butyl N-(cyclopropylmethyl)-N-(1- {6-[5-(methoxymethoxy)-2-methyl-1,3-benzoxazol-6-yl]-1,5-nap hthyridin-2-yl}pyrrolidin-3- yl)carbamate (D14, 350 mg). LCMS: (ES, m/z):560 [M+H] ⁺ Synthesis of Intermediate D15 A solution of Intermediate D14 (350 mg, 0.625 mmol, 1 equiv) in HCl(gas) in 1,4-dioxane (1 mL) and MeOH (2 mL) was stirred for 1 h at room temperature and then concentrated under reduced pressure. The crude product was purified by Preparative chiral HPLC following Condition 11, Gradient 1 to afford 6-(6-{3-[(cyclopropylmethyl)amino]pyrrolidin-1-yl}-1,5- naphthyridin-2-yl)-2-methyl-1,3-benzoxazol-5-ol (D15, 15.5 mg) to QC. LCMS: (ES, m/z): 416 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 14.53 (s, 1H), 8.45 – 8.39 (m, 2H), 8.10 (dd, J = 15.2, 9.2 Hz, 2H), 7.16 (d, J = 9.3 Hz, 1H), 7.12 (s, 1H), 3.74 (dd, J = 10.8, 5.9 Hz, 1H), 3.68 (s, 1H), 3.58 (s, 1H), 3.48 – 3.41 (m, 1H), 2.61 (s, 3H), 2.46 (d, J = 6.7 Hz, 2H), 2.13 (dq, J = 12.8, 6.6 Hz, 1H), 1.88 – 1.85 (m, 2H), 0.96 – 0.82 (m, 1H), 0.45 – 0.37 (m, 2H), 0.17 – 0.05 (m, 2H). The intermediate D15 (90 mg, 0.217 mmol, 1 equiv) was purified by preparative chiral HPLC following Condition 4, Gradient 11 to afford Compound 291 (First peak, 17.7 mg) and Compound 292 (Second peak, 18.5 mg). Absolute stereochemistry of the chiral compounds was assigned arbitrarily. Compound 291 (First peak): LCMS: (ES, m/z): 416 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d6) δ 14.53 (s, 1H), 8.46 – 8.39 (m, 2H), 8.11 (dd, J = 17.2, 9.2 Hz, 2H), 7.17 (d, J = 9.3 Hz, 1H), 7.12 (s, 1H), 3.75 (dd, J = 9.9, 5.4 Hz, 1H), 3.68 (s, 1H), 3.58 (d, J = 8.0 Hz, 1H), 3.57 – 3.48 (m, 1H), 3.47 – 3.38 (m, 1H), 2.61 (s, 3H), 2.48 (s, 2H), 2.20 – 2.10 (m, 1H), 1.89 – 1.88 (m, 1H), 0.95 – 0.85 (m, 1H), 0.47 – 0.38 (m, 2H), 0.19 – 0.10 (m, 2H). Compound 292 (Second peak). LCMS: (ES, m/z): 416 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO- d ₆ ) δ 14.54 (s, 1H), 8.46 – 8.39 (m, 2H), 8.16 – 8.05 (m, 2H), 7.17 (d, J = 9.3 Hz, 1H), 7.12 (s, 1H), 3.78 – 3.66 (m, 2H), 3.58 (d, J = 8.0 Hz, 1H), 3.57 – 3.48 (m, 1H), 3.47 – 3.38 (m, 1H), 2.61 (s, 3H), 2.47 (d, J = 6.4 Hz, 2H), 2.14 (dd, J = 12.5, 6.3 Hz, 1H), 1.89 – 1.88 (m, 1H), 0.94 – 0.84 (m, 1H), 0.46 – 0.37 (m, 2H), 0.18 – 0.10 (m, 2H). Example 202: Synthesis of Compound 932 Synthesis of Intermediate D17 A solution of 4-amino-6-chloropyridine-3-carbaldehyde (D16, 5 g, 31.935 mmol, 1 equiv), Yb(OTf) ₃ (4.95 g, 7.984 mmol, 0.25 equiv), and 2-bromo-1,1-dimethoxy-ethane, (16.19 g, 95.805 mmol, 3 equiv) in ACN (50 mL) was stirred for 16 h at 0~80°C under nitrogen atmosphere, and later allowed to cool to room temperature. The precipitated solids were collected by filtration, washed with ACN (1x50 mL), and the residue was purified by silica gel column chromatography and eluted with PE / EA (5:1) to afford 3-bromo-7-chloro-1,6- naphthyridine (D17, 2 g). LCMS: (ES, m/z): 243 [M+H] ⁺ Synthesis of Intermediate D18 A solution of Intermediate D17 (300 mg, 1.232 mmol, 1 equiv), tert-butyl N-methyl-N- (pyrrolidin-3-yl)carbamate (296 mg, 1.478 mmol, 1.2 equiv), SPhos (101 mg, 0.246 mmol, 0.2 equiv), Pd2(dba) ₃ (113 mg, 0.123 mmol, 0.1 equiv), and Cs2CO ₃ (1204 mg, 3.696 mmol, 3 equiv) in 1,4-dioxane (6 mL) was stirred for 2h at 100°C under nitrogen atmosphere and allowed to cool to room temperature. The resulting mixture was extracted with EA (1 x 30mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford tert-butyl N-[1-(7-chloro-1,6-naphthyridin-3-yl)pyrrolidin-3-yl]-N-meth ylcarbamate (D18, 300 mg). LCMS: (ES, m/z): 363 [M+H] ⁺ .

To a stirred solution of Intermediate D18 (90 mg, 0.248 mmol, 1 equiv) and K ₂ CO ₃ (69 mg, 0.496 mmol, 2 equiv), XPhos (12 mg, 0.025 mmol, 0.1 equiv), XPhos Pd G3 (21 mg, 0.025 mmol, 0.1 equiv) in 1,4-dioxane (4.5 mL) and water (0.9 mL) was added 6-(methoxymethoxy)- 2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) indazole (99 mg, 0.298 mmol, 1.2 equiv) in portions at 70°C under nitrogen atmosphere and the resulting mixture was stirred for 16h at 70°C and subsequently allowed to cool to room temperature. The resulting mixture was extracted with EA (1 x 20mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford tert-butyl N-(1-{7-[6-(methoxymethoxy)-2,7- dimethylindazol-5-yl]-1,6-naphthyridin-3-yl}pyrrolidin-3-yl) -N-methylcarbamate (D19, 35 mg). LCMS: (ES, m/z): 533 [M+H] ⁺ . Synthesis of Compound 932 A solution of Intermediate D19 (35 mg, 0.066 mmol, 1 equiv) in DCM (1 mL) and CF ₃ COOH (0.5 mL) was stirred for 1h at room temperature. The resulting mixture was concentrated under reduced pressure, and the crude product was purified by Prep-HPLC following Condition 3, Gradient 15 as previously described to afford 2,7-dimethyl-5-{3-[3-(methylamino)pyrrolidin-1- yl]-1,6-naphthyridin-7-yl}indazol-6-ol (Compound 932, 15.9 mg). LCMS: (ES, m/z): 389 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 13.66 (s, 1H), λ.20 (s, 1H), 8.86 (d, J = 2.9 Hz, 1H), 8.48 (s, 1H), 8.34 (s, 1H), 8.27 (s, 1H), 7.27 (d, J = 2.9 Hz, 1H), 4.13 (s, 3H), 3.63 (m, 1H), 3.54 (m, 1H), 3.48 (m, 1H),3.29 – 3.21 (m, 1H), 2.36 (s, J = 11.0 Hz, 3H), 2.34 (s, J = 11.0 Hz, 3H), 2.16 (dq, J = 13.1, 7.0 Hz, 1H), 1.90 (dt, J = 11.9, 6.1 Hz, 2H). Example 203: Synthesis of Compounds 312, 313, and 314 Synthesis of Intermediate D21 To a stirred solution of 5-methoxy-2,4-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxabo rolan-2- yl)-1,3-b enzoxazole (D20, 300 mg, 0.990 mmol, 1 equiv) and tert-butyl N-[1-(6-chloro-1,5-n aphthyridin-2 -yl) pyrrolidin-3-yl]-N-isopropylcarbamate (580.23 mg, 1.485 mmol, 1.5 equiv) in dioxane (16 mL) and H ₂ O (4 mL) were added Pd(dppf)Cl ₂ CH ₂ Cl ₂ (80.61 mg, 0.099 mmol, 0.1 equiv) and K ₃ PO ₄ (630.14 mg, 2.970 mmol, 3 equiv) in portions at room temperature. The mixture was stirred for 2h at 100°C under nitrogen atmosphere and later allowed to cool to room temperature. The reaction was quenched with water and extracted with EtOAc (3 x 20mL). The combined organic layers were washed with water (3x20 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford tert-butyl N-isopropyl-N-{1-[6- (5-methoxy-2,4- di me thyl-1,3-benzoxazol-6-yl)-1,5-naphthyridin- 2-y l]pyr roledin-3- yl}carbamate (D21, 310 mg). LCMS: (ES, m/z): 532 [M+H]. BBr3 (1319.38 mg, 5.270 mmol, 10 equiv) was added dropwise over 10min at 0°C to a 20mL 4- necked round-bottom flask containing Intermediate D21 (280 mg, 0.527 mmol, 1 equiv) and DCM (6 mL) initially mixed at room temperature. The resulting mixture was stirred for additional three days at room temperature, quenched by the addition of MeOH (3mL) at 0°C, and extracted with EtOAc (1 x 20mL). The combined organic layers were washed with water (3x10 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 1, Gradient 29 as previously described to afford 6-{6-[3-(isopropylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2- yl}-2,4- dimethyl-1,3-benzoxazol-5-ol (Compound 312, 45.2 mg). LCMS: (ES, m/z): 418 [M+H]. ¹ H NMR: (400 MHz, DMSO-d6) δ 14.λλ (s, 1H), 8.41 (d, J = 9.3 Hz, 1H), 8.25 (s, 1H), 8.13 (d, J = 9.3 Hz, 1H), 8.07 (d, J = 9.1 Hz, 1H), 7.16 (d, J = 9.3 Hz, 1H), 3.78 (d, J = 8.3 Hz, 1H), 3.70 (s, 1H) ₃ .52 (s, 2H), 3.32 (s, 1H), 2.85 (p, J = 6.3 Hz, 1H), 2.61 (s, 3H), 2.40 (s, 3H), 2.15 (dt, J = 12.4, 6.3 Hz, 1H), 1.79 (dt, J = 14.1, 7.2 Hz, 1H), 1.72 (s, 1H), 1.02 (dd, J = 6.2, 4.6 Hz, 6H). Compound 312 (110 mg, 0.263 mmol, 1 equiv) was purified by Preparative chiral HPLC following Condition 4, Gradient 12 as previously described to afford 6-{6-[(3S)-3- (isopropylamino)pyrrolidin-1-yl]-1,5-naphthyridin-2-yl}-2,4- dimethyl-1,3-benzoxazol-5-ol (Compound 313, 36.4 mg) and 6-{6-[(3R)-3-(isopropylamino)pyrrolidin-1-yl]-1,5-naphthyrid in- 2-yl}-2,4-dimethyl-1,3-benzoxazol-5-ol (Compound 31436.8 mg). Absolute stereochemistry of the chiral compounds was assigned arbitrarily. Compound 313: (ES, m/z): 418 [M+H]. ¹ H NMR: (400 MHz, DMSO-d6) δ 14.λλ (s, 1H), 8.42 (d, J = 9.3 Hz, 1H), 8.26 (s, 1H), 8.14 (d, J = 9.3 Hz, 1H), 8.08 (d, J = 9.1 Hz, 1H), 7.17 (d, J = 9.3 Hz, 1H), 3.79 (s, 1H), 3.71 (s, 1H), 3.53 (s, 2H), 3.33 (s, 1H), 2.90 – 2.82 (m, 1H), 2.61 (s, 3H), 2.40 (s, 3H), 2.16 (dd, J = 11.6, 5.9 Hz, 1H), 1.81 (s, 2H), 1.02 (dd, J = 6.2, 4.5 Hz, 6H). Compound 314: LCMS: (ES, m/z): 418 [M+H]. ¹ H NMR: (400 MHz, DMSO-d6) δ 14.λλ (s, 1H), 8.41 (d, J = 9.2 Hz, 1H), 8.25 (s, 1H), 8.14 (d, J = 9.3 Hz, 1H), 8.08 (d, J = 9.1 Hz, 1H), 7.17 (d, J = 9.3 Hz, 1H), 3.79 (s, 1H), 3.70 (s, 1H), 3.53 (t, J = 9.2 Hz, 2H), 3.33 (s, 1H), 2.87 (t, J = 6.4 Hz, 1H), 2.61 (s, 3H), 2.40 (s, 3H), 2.16 (dd, J = 11.9, 6.3 Hz, 1H), 1.81 (s, 2H), 1.03 (dd, J = 6.2, 4.5 Hz, 6H). Example 204: Synthesis of Compound 501 Synthesis of Intermediate D22 Into a 250 mL round bottom flask were added 2-amino-5-chlorobenzonitrile (5 g, 32.770 mmol, 1 eq uiv), triphenylphosphine oxide (0.91 g, 3.277 mmol, 0.1 equiv), chlorobenzene (120 mL) and triethylamine (0.03 g, 0.328 mmol, 0.01 equiv) at room temperature. The resulting mixture was stirred for 0.5 h at 0 ^o C before adding triphosgene (11.67 g, 39.324 mmol, 1.2 equiv) and stirring for an additional 5 h at 120 ^o C.. The reaction was quenched by the addition of water (200 mL) at room temperature, the aqueous layer was extracted with EtOAc (2x100 mL) and dried over Na ₂ SO ₄ . The resulting mixture was concentrated under reduced pressure, purified by silica gel column chromatography, and eluted with PE / EA (3:1) to afford 2,4,6- trichloroquinazoline (D22, 5.5 g). LCMS: (ES, m/z): 233 [M+H] ⁺ . Synthesis of Intermediate D23 Into a 100 mL round bottom flask were added Intermediate D22 (2 g, 8.566 mmol, 1 equiv), DMF (40mL), tributyl(1-ethoxyethenyl)stannane (3.71 g, 10.279 mmol, 1.2 equiv) and palladium chloride; bis(triphenylphosphine) (0.60 g, 0.857 mmol, 0.1 equiv) at room temperature. The resulting mixture was stirred for 3h at 60°C under nitrogen atmosphere and subsequently quenched by the addition of water (100 mL) at room temperature. The aqueous layer was extracted with EtOAc (2x100 mL) and dried over Na ₂ SO4. The resulting mixture was concentrated under reduced pressure, purified by silica gel column chromatography, and eluted with PE / EA (3:1) to afford 2,6-dichloro-4-(1-ethoxyet henyl)quin azoline (D23, 1.7 g). LCMS: (ES, m/z): 269 [M+H] ⁺ . Synthesis of Intermediate D24 Into a 40 mL vial were added Intermediate D23 (1.6 g, 5.945 mmol, 1 equiv), dioxane (10 mL), water (10 mL), sodium periodate (1.27 g, 5.945 mmol, 1 equiv). and tetraoxo(potassio) manganese (1.88 g, 11.890 mmol, 2 equiv) at room temperature. The resulting mixture was stirred for 3 h at 25°C and afterwards diluted with water (30 mL). The aqueous layer was extracted with EtOAc (2x100 mL) and dried over Na ₂ SO ₄ . The resulting mixture was concentrated under reduced pressure, the residue purified by silica gel column chromatography, and eluted with PE / EA (3:1) to afford ethyl 2,6-dichloroquinazoline-4-carboxylate (D24, 940 mg). LCMS: (ES, m/z): 271 [M+H] ⁺ . Synthesis of Intermediate D25 To a solution of Intermediate D24 (330 mg, 1.217 mmol, 1 equiv) and 6-methox y-2,7-dimethyl- 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazole (441.40 mg, 1.460 mmol, 1.2 equiv) in dioxane (6 mL) and H ₂ O (0.5 mL) were added K ₂ CO ₃ (504.70 mg, 3.651 mmol, 3 equiv) and Pd(dppf)Cl ₂ (89.07 mg, 0.122 mmol, 0.10 equiv) . After stirring for 6 h at 80 ^o C under a nitrogen atmosphere, it was concentrated under reduced pressure, the residue was purified by silica gel column chromatography and lastly eluted with THF/PE (1:1) to afford tert-butyl 4-[(5- fluoro-7-{8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl}cinnol in-4-yl)amino]piperidine-1- carboxylate (73 mg, 78.90%)methyl 6-chloro-2-(6-methoxy-2,7-dimethylindazol-5- yl)quinazoline-4-carboxylate (D25, 456 mg). LCMS: (ES, m/z): 411 [M+H] ⁺ . Synthesis of Intermediate D26 Into a 40 mL vial were added Intermediate D25 (310 mg, 0.781 mmol, 1 equiv), Cs2CO ₃ (765.94 mg, 2.343 mmol, 3 equiv), tert-butyl piperazine-1-carboxylate (174.60 mg, 0.937 mmol, 1.2 equiv), Pd2(dba) ₃ (71.54 mg, 0.078 mmol, 0.1 equiv), XPhos (74.48 mg, 0.156 mmol, 0.2 equiv) and dioxane (6 mL) at room temperature. The resulting mixture was stirred for 3h at 80°C under nitrogen atmosphere and later concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with THF/ EA (1:1) to afford methyl 6- [4-(tert-butoxycarbonyl) piperazin-1-yl]-2- (6-methoxy-2,7-dimethylindazol-5-yl)quinazoline-4- carboxylate (D26, 240 mg). LCMS: (ES, m/z): 561 [M+H] ⁺ . Synthesis of Intermediate D27 Into a 40 mL vial were added Intermediate D26 (240 mg, 0.439 mmol, 1 equiv), tetrahydrofuran (4 mL), water (2 mL) and lithiumol (15.77 mg, 0.658 mmol, 1.5 equiv) at room temperature. The resulting mixture was stirred for 3 h at 50°C and subsequently diluted with water (30 mL). The mixture was acidified to pH 5 with HCl (aq.), and then the aqueous layer was extracted with EtOAc (2x50 mL) and concentrated under reduced pressure, resulting in 6-[4-(tert- butoxycarbonyl) pipera zin-1-yl]-2-(6-methoxy-2,7-dimethylindazol-5-yl)quinazoline- 4- carboxylic acid (D27, 210 mg). LCMS: (ES, m/z): 533 [M+H] ⁺ . Synthesis of Intermediate D28 Into a 40 mL vial were added Intermediate D27 (200 mg, 0.376 mmol, 1 equiv), methylamine (34.99 mg, 1.128 mmol, 3 equiv), HATU (214.18 mg, 0.564 mmol, 1.5 equiv), dimethylformamide (6 mL) and DIEA (145.60 mg, 1.128 mmol, 3 equiv) at room temperature. The resulting mixture was stirred for 2 h at room temperature and later quenched by the addition of water (10 mL) at room temperature. The aqueous layer was extracted with EtOAc (2x10 mL) and then dried over Na ₂ SO4. The resulting mixture was concentrated under reduced pressure, the residue was purified by silica gel column chromatography, and finally eluted with PE / EA (3:1) to afford tert-butyl 4-[2-(6-methoxy-2,7-dimethylindazo l-5-yl)-4-(methylcarbamoyl) quinazolin-6-yl]piperazine-1-carboxylate (D28, 170 mg). LCMS: (ES, m/z): 546 [M+H] ⁺ . Synthesis of Intermediate D29 Into an 8 mL round-bottom flask were added Intermediate D28 (80 mg, 0.147 mmol, 1 equiv), NMP (2 mL), K ₂ CO ₃ (20.41 mg, 0.147 mmol, 1 equiv) and 4-methylbenzenethiol (36.42 mg, 0.294 mmol, 2 equiv) at 25 ^o C. The resulting mixture was stirred for 12 h at 150 ^o C and later allowed to cool to 25 ^o C. The resulting mixture was concentrated under reduced pressure, the residue was purified by silica gel column chromatography, and lastly eluted with THF / EA (1:1) to afford tert-butyl 4-[2-(6-hydroxy-2,7-dimethylindazol-5-yl)-4- (methylcarbamoyl) quinazolin- 6-yl]piperazine-1-carboxylate (D29, 50 mg). LCMS: (ES, m/z): 532 [M+H] ⁺ . Synthesis of Compound 501 Into an 8 mL vial were added Intermediate D29 (50 mg, 0.094 mmol, 1 equiv), DCM (1 mL) and trifluoroacetaldehyde (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature. The crude product was then purified by Prep-HPLC following Condition 7, Gradient 3 as previously described to afford 2-(6-hydroxy-2,7-di methylindazol -5-yl)-N-methyl -6-(piperaz in-1-yl)quinazoline-4-carboxamide (Compound 501, 6.9 mg). LCMS: (ES, m/z): 432 [M+H] ⁺ . ¹ H NMR: (300 MHz, DMSO-d6) δ 13.33 (s, 1H), 9.24 (d, J = 5.0 Hz, 1H), 9.12 (s, 1H), 8.86 (s, 2H), 8.43 (s, 1H), 8.25 (d, J = 2.6 Hz, 1H), 8.15 – 7.97 (m, 2H), 4.17 (s, 3H), 3.56 (d, J = 5.6 Hz, 4H), 2.98 (d, J = 4.7 Hz, 3H), 2.41 (s, 3H). Example 205: Synthesis of Compounds 339 and 340 Synthesis of Intermediates D32 and D33 Into a 40mL round-bottom flask were added the isomers 5-methoxy-1,2-dimethyl-6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzodiazole (D30 and D31, 450 mg, 0.596 mmol, 1 equiv, 40%) and N-tert-butyl-1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3- amine (236 mg, 0.775 mmol, 1.3 equiv), together with dioxane (16 mL) and H ₂ O (4 mL) at room temperature. To the above mixture was added K ₃ PO ₄ (379 mg, 1.788 mmol, 3 equiv) and Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (48.52 mg, 0.060 mmol, 0.1 equiv) in portions over 5 min, and the mixture was subsequently stirred for additional 3 h at 90 °C then allowed to cool to room temperature. The resulting mixture was extracted with EA (3 x 30 mL), the combined organic layers were washed with water (3 x 30 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by reverse flash chromatography following Condition 3, Gradient as previously described to afford the isomers N-tert-butyl-1-[6-(6-methoxy-2,3- dimethyl-1,3-benzodiazol-5-yl)-1,5-naphthyridin-2-yl]pyrroli din-3-amine (D32 and D33, 45 mg) as white solid. LCMS: (ES, m/z): 445 [M+H]. Synthesis of Compounds 339 and 340 To a stirred solution of Intermediates D32 and D33 (45 mg, 0.101 mmol, 1 equiv) in DCM (2 mL) were added BBr ₃ (127 mg, 0.505 mmol, 5 equiv) dropwise at 0 °C. The mixture was stirred for 5 days at room temperature, quenched by the addition of MeOH (6 mL) at 0 °C and thereafter concentrated under vacuum. The resulting mixture was extracted with CH ₂ Cl ₂ (3 x 30 mL), the combined organic layers were washed with water (3 x 30 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 2, Gradient 13 as previously described to afford 6-{6-[3-(tert- butylamin o)pyrrolidin-1-yl]-1,5-na phthyridi n-2-yl}-1,2-dimethyl-1,3-benzodiazol-5-ol (Compound 339, 31.7 mg) and 6-{6-[3-(te rt-butylamino) pyrrolidin-1-yl] -1,5-naphthyridin-2- yl}-2,3-dimethyl-1,3-benzodiazol-5-ol (Compound 340, 10.7 mg). Compound 339: LCMS: (ES, m/z): 431 [M+H]. ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 14.10 (s, 1H), 8.50 (d, J = 9.3 Hz, 1H), 8.22 (s, 1H), 8.10 (dd, J = 9.2, 2.3 Hz, 2H), 7.14 (d, J = 9.3 Hz, 1H), 6.95 (s, 1H), 3.97 – 3.88 (m, 1H), 3.78 (s, 4H), 3.52 (d, J = 8.6 Hz, 1H), 3.47 (d, J = 9.3 Hz, 1H), 3.29 (d, J = 4.5 Hz, 3H), 3.19 – 3.10 (m, 1H), 2.47 – 2.18 (m, 1H), 1.92 – 1.81 (m, 1H), 1.13 (s, 9H). Compound 340: LCMS: (ES, m/z): 431 [M+H]. ¹ H NMR: (400 MHz, Chloroform-d) δ 15.01 (s, 1H), 8.1λ – 8.10 (m, 1H), 8.08 (d, J = 9.1 Hz, 2H), 7.98 (d, J = 9.2 Hz, 1H), 6.91 (d, J = 9.2 Hz, 1H), 6.87 (s, 1H), 4.08 – 3.99 (m, 1H), 3.90 – 3.82 (m, 1H), 3.68 (s, 3H), 3.66 – 3.57 (m, 2H), 3.60 – 3.50 (m, 1H), 2.58 (s, 3H), 2.38 – 2.26 (m, 1H), 1.92 – 1.85 (m, 1H), 1.25 (s, 1H), 1.19 (s, 9H). Example 206: Synthesis of Compound 344 A mixture of 2-bromo-5,7-dimethylimidazo[1,2-c] pyrimidine (D34, 57.41 mg, 0.25 mmol, 1.10 equiv) and Pd(dtbpf)Cl ₂ (15.05 mg, 0.02 mmol, 0.10 equiv) in dioxane (2 mL) was stirred for 30 min at 100°C under nitrogen atmosphere. N-tert-butyl-1-[6-(trimethylstannyl)-1,5-naphthyridin- 2-yl]pyrrolidin-3-amine (100 mg, 0.23 mmol, 1.00 equiv) was added and the mixture was stirred for 2 h at 50°C. The residue was purified by silica gel column chromatography and eluted with PE/EA (5:1) to afford crude product, which was purified by Prep-HPLC with the following conditions (2#SHIMADZU (HPLC-01)): Column, YMC-Actus Triart C ₁₈ , 30*150 mm, 5µm; mobile phase, Water (10 mmol/L NH ₄ HCO ₃ ) and ACN (10% ACN up to 70% in 8 min). This resulted in N-tert-butyl-1-(6-{5,7-dimethylimidazo[1,2-c] pyrimidin-2-yl}-1,5-naphthyridin -2- yl)pyrrolidin-3-amine (10.8 mg, 11.24%) as a yellow solid. LCMS: (ES, m/z):416 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 8.36 (d, J = 0.8 Hz, 1H), 8.27 (d, J = 8.7 Hz, 1H), 8.05 (d, J = 9.3 Hz, 1H), 8.01 – 7.94 (m, 1H), 7.34 (s, 1H), 7.12 (d, J = 9.3 Hz, 1H), 3.85 (s, 1H), 3.71 (s, 1H), 3.52 (s, 1H), 3.48 (td, J = 10.2, 9.4, 6.9 Hz, 1H), 3.12 (dd, J = 10.4, 7.2 Hz, 1H), 2.85 (s, 3H), 2.46 – 2.41 (m, 3H), 2.22 – 2.12 (m, 1H), 1.76 (dt, J = 11.5, 8.5 Hz, 1H), 1.69 (s, 1H), 1.09 (s, 9H). Example 207: Synthesis of Compounds 351 and 352 Synthesis of Intermediate D36 Into a 40 mL vial was added to 6-bromo-5-methoxy-2,4-dimethylbenzo[d]oxazole (D35, 160 mg, 0.624 mmol, 1 equiv) and DCE (1.5 mL), followed by dropwise addition of BBr ₃ (2 ml, 3 equiv, 1 M in dioxane) at 0°C for 10 min. The resulting mixture was warmed to room temperature, stirred for 1 h and then quenched by the addition of 10 mL of MeOH at 0 ^o C, whereupon the solvent was removed in vacuo. The pH of the solution was adjusted to7 with saturated NaHCO ₃ , extracted with 3x10 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated, which resultingly afforded 140 mg of 6-bromo-2,4- dimethylbenzo[d]oxazol-5-ol (D36, crude) which was used directly in the subsequent step. Synthesis of Intermediate D37 Into a 40ml vial purged and maintained with an inert atmosphere of nitrogen, was placed Intermediate D36 (140 mg, 0.62 mmol, 1.00 equiv), tert-butyl ((1r,3r)-3-fluorocyclobutyl)(1-(6- (trimethylstannyl)-1,5-naphthyridin-2-yl)pyrrolidin-3-yl)car bamate (340mg, 0.62 mmol, 1.00 equiv), Pd(dtbpf)Cl ₂ (40 mg, 0.062 mmol, 0.1 equiv) and 1,4-dioxane (20 mL). The resulting solution was stirred for 2 h at 100°C, subsequently cooled to room temperature and extracted with 3 x 20 mL of ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate and concentrated. The residue was applied onto a silica gel column with ethyl acetate/hexane (1:1), resulting in 100.0 mg of solid containing Intermediate D37. LCMS: (ES, m/z): 548 [M+H] ⁺ . Synthesis of Intermediate D38 Into a 40-mL round-bottom flask was placed Intermediate D37 (100 mg, 0.183 mmol, 1.00 equiv), MeOH (1.00 mL), HCl (g) in dioxane (1.00ml, 1 mol/L, 5 equiv. ). The resulting solution was stirred for 1 h at room temperature, concentrated, and the crude product was purified by prep-HPLC following Condition 3, Gradient 25 as previously described to afford 40 mg of 7- fluoro-5-(6-(3-(((1r,3r)-3-fluorocyclobutyl)amino)pyrrolidin -1-yl)-1,5-naphthyridin-2-yl)-2- methyl-2H-indazol-6-ol (D38) . LCMS: (ES, m/z): 448 [M+H] ⁺ . Synthesis of Compounds 351 and 352 Intermediate D38 (40 mg) was purified by preparative chiral HPLC following Condition 4, Gradient 7 as previously described to afford 11.3 mg 6-(6-((R)-3-(((1r,3R)-3- fluorocyclobutyl)amino)pyrrolidin-1-yl)-1,5-naphthyridin-2-y l)-2,4-dimethylbenzo[d]oxazol-5- ol (Compound 352) and 11.1 mg 6-(6-((S)-3-(((1r,3S)-3-fluorocyclobutyl)amino)pyrrolidin-1- yl)-1,5-naphthyridin-2-yl)-2,4-dimethylbenzo[d]oxazol-5-ol (Compound 351) LCMS: (ES, m/z): 448 [M+H] ⁺ . Absolute stereochemistry of the compounds has been assigned arbitrarily. ¹ H NMR of Compound 352:(400 MHz, DMSO-d6)μ δ 14.λ7 (s, 1H), 8.43 (d, J = λ.3 Hz, 1H), 8.26 (s, 1H), 8.18 (d, J = 9.2 Hz, 1H), 8.09 (d, J = 9.1 Hz, 1H), 7.20 (d, J = 9.3 Hz, 1H), 5.35 – 5.09 (m, 1H), 3.82 – 3.75 (m, 1H), 3.75 – 3.64 (m, 2H), 3.63 – 3.51 (m, 1H), 3.46 (d, J = 12.1 Hz, 0H), 2.61 (s, 3H), 2.47 – 2.27 (m, 5H), 2.31 – 2.05 (m, 3), 2.05 – 1.85 (m, 1H). ¹ H NMR of Compound 351: (400 MHz, DMSO-d6): δ 14.λ6 (s, 1H), 8.43 (d, J = 9.3 Hz, 1H), 8.26 (s, 1H), 8.17 (d, J = 9.2 Hz, 1H), 8.09 (d, J = 9.1 Hz, 1H), 7.19 (d, J = 9.3 Hz, 1H), 5.23 (ddd, J = 59.8, 6.4, 3.1 Hz, 1H), 2.61 (s, 3H), 2.46 – 2.36 (m, 5H), 2.35 – 2.13 (m, 3H), 1.93 (d, J = 15.6 Hz, 1H) The retention time of the first peak is 2.10 min, which has been assigned to Compound 352. The retention time of the second peak is 2.64 min, which has been assigned to Compound 351. Example 208: Synthesis of Compounds 356 and 383 Synthesis of Intermediate D40 To a stirred solution of 2,6-dichloro-1,5-naphthyridine ( D39, 500 mg, 2.512 mmol, 1 equiv) and tert-butyl 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6 -dihydro-2H-pyridine-1- carboxylate (1.05 g, 3.266 mmol, 1.3 equiv) in dioxane (16 mL) and H ₂ O (4 mL) were added Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (205 mg, 0.251 mmol, 0.1 equiv) and K ₂ CO ₃ (1.04 g, 7.536 mmol, 3 equiv) in portions at room temperature, stirred for additional 3 h at 80 °C, and afterward allowed to cool to room temperature. The resulting mixture was extracted with EA (3 x 30 mL), the combined organic layers were washed with water (3 x 30 mL), dried over anhydrous Na ₂ SO4, and the resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (3:1) to afford tert-butyl 4-(6-chloro-1,5- naphthyridin-2-yl)-2-methyl-5,6-dihydro -2H-pyridine-1-carboxylate (D40, 500 mg). LCMS: (ES, m/z): 360 [M+H]. Synthesis of Intermediate D41 To a stirred solution of Intermediate D40 (450 mg, 1.251 mmol, 1 equiv) and 7-fluoro-6- (methoxymethoxy)-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)indazole (630 mg, 1.876 mmol, 1.5 equiv) in 1,4-dioxane (16 mL) and H ₂ O (4 mL) were added Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (102 mg, 0.125 mmol, 0.1 equiv) and K ₃ PO ₄ (796 mg, 3.753 mmol, 3 equiv) in portions at room temperature. The resulting mixture was stirred for additional 4 h at 90°C, later allowed to cool to room temperature and extracted with EA (3 x 30 mL). The combined organic layers were washed with water (3 x 30 mL), dried over anhydrous Na ₂ SO ₄ , and the resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford tert-butyl 4-{6-[7-fluoro-6-(methoxymethoxy)-2- methylindazol-5-yl] -1,5-naphthyridin-2-yl} -2-methyl-5,6-dihydro-2H-pyridine-1-carboxylate (D41, 290 mg). LCMS: (ES, m/z): 534 [M+H]. Synthesis of Intermediate D42 A solution of Intermediate D41 (260 mg, 0.487 mmol, 1.00 equiv) and Pd/C (518 mg, 4.870 mmol, 10 equiv) in MeOH (30 mL) was stirred for 8 h at room temperature under H ₂ atmosphere. The resulting mixture was filtered, the filter cake was washed with MeOH (3 x 10mL) and concentrated under reduced pressure. The resulting mixture and MnO ₂ (424 mg, 4.870 mmol, 10 equiv) in DCE (30 mL) was stirred for 2 h at 80°C, filtered, washed with CH ₂ Cl ₂ (3 x 10 mL). and concentrated under reduced pressure, affording tert-butyl 4-{6-[7-fluoro-6- (methoxymethoxy)-2-methylindazol-5-yl]-1,5-naphthyridin-2-yl }-2-methylpiperidine-1- carboxylate (D42, 280 mg, 96.56%). LCMS: (ES, m/z): 536 [M+H]. Synthesis of Intermediate D43 To a stirred solution of Intermediate D42 (250 mg, 0.467 mmol, 1 equiv) in MeOH (10 mL) was added HCl(gas)in 1,4-dioxane (5 mL) dropwise at room temperature. The resulting mixture was stirred for additional 3 h at room temperature and concentrated under vacuum to afford 7-fluoro- 2-methyl-5-[6-(2-methylpiperidin-4-yl)-1,5-naphthyridin-2-yl ]indazol-6-ol (D43, 150 mg). LCMS: (ES, m/z): 392 [M+H]. The crude Intermediate D43 (150 mg, 0.766 mmol, 1 equiv) ) was purified by preparative chiral HPLC following Condition 4, Gradient 13 as previously described to afford 7-fluoro-2-methyl-5- {6-[(2R,4R)-2-methylpiperidin-4-yl]-1,5-naphthyridin-2-yl}in dazol-6-ol (Compound 383, 22.6 mg, 7.53%) and 7-fluoro-2-methyl-5-{6-[(2S,4R)-2-methylpiperidin-4-yl]-1,5- naphthyridin-2- yl}indazol-6-ol (Compound 356, 7.3 mg). Absolute stereochemistry of the compounds was assigned arbitrarily. Compound 383: LCMS: (ES, m/z): 392 [M+H]. ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 14.08 (s, 1H), 8.63 (d, J = 9.3 Hz, 1H), 8.57 (dd, J = 9.0, 1.9 Hz, 2H), 8.54 – 8.38 (m, 1H), 8.46 (s, 1H), 7.79 (d, J = 8.7 Hz, 1H), 4.18 (s, 3H), 3.17 – 3.01 (m, 2H), 2.80 – 2.77 (m, 2H), 1.91 (ddd, J = 15.1, 9.2, 6.8 Hz, 2H), 1.69 (qd, J = 12.4, 4.1 Hz, 1H), 1.43 (q, J = 12.0 Hz, 1H), 1.08 (d, J = 6.3 Hz, 3H). ¹⁹ F NMR: (376 MHz, DMSO-d ₆ ) δ -157.95. Compound 356: LCMS: (ES, m/z): 392 [M+H]. ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 14.07 (s, 1H), 8.64 (d, J = 9.3 Hz, 1H), 8.58 (d, J = 1.0 Hz, 1H), 8.56 (d, J = 2.7 Hz, 1H), 8.52 (dd, J = 9.1, 0.8 Hz, 1H), 8.47 (dd, J = 8.6, 0.9 Hz, 1H), 7.84 (d, J = 8.8 Hz, 1H), 4.18 (s, 3H), 3.48 – 3.41 (m, 1H), 3.01 – 2.90 (m, 1H), 2.96 (s, 2H), 2.18 (ddd, J = 13.4, 7.6, 3.9 Hz, 1H), 2.11 – 2.01 (m, 1H), 1.93 (d, J = 11.4 Hz, 1H), 1.73 (dt, J = 12.9, 5.8 Hz, 1H), 1.18 (d, J = 6.6 Hz, 3H). ¹⁹ F NMR: (376 MHz, DMSO-d6) δ -157.94. Example 209: Synthesis of Compound 364 Synthesis of Intermediate D45 A mixture of 1-(2,6-dichloro-1,5-naphthyridin-4-yl) ethanol (395 mg, 1.625 mmol, 1 equiv)1- (2,6-dichlo ro-1,5-naphthyridin-4-yl) ethanol (D44, 395 mg, 1.625 mmol, 1 equiv), tert-butyl piperazine-1-carboxylate (363.18 mg, 1.950 mmol, 1.2 equiv), Pd ₂ (dba) ₃ (14.88 mg, 0.016 mmol, 0.01 equiv) and K ₃ PO ₄ (1034.74 mg, 4.875 mmol, 3 equiv) in dioxane (8 mL) was stirred for 5h at 80°C under nitrogen atmosphere, concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE:EA = 4:1 to afford tert-butyl 4- [6-chloro-8-(1-hydrox yethyl)-1,5-naphthyridin-2-yl]piperazine-1-carboxylate (D45, 93 mg). LCMS: (ES, m/z): 393 [M+H] ⁺ . Synthesis of Intermediate D46 A solution of Intermediate D45 (65 mg, 0.165 mmol, 1 equiv) in dioxane (2 mL) and H ₂ O (0.2 mL) was treated with 6-(methoxymethoxy)- 2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-2H-indazole (65.95 mg, 0.198 mmol, 1.2 equiv), XPhos Pd G3 (14.00 mg, 0.017 mmol, 0.1 equiv) and K3PO4 (70.24 mg, 0.330 mmol, 2 equiv) for 3h at 80°C under nitrogen atmosphere and later allowed to cool down to room temperature. The resulting mixture was extracted with DCM, the combined organic layers were dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE:EA = 3:1 to afford tert-butyl 4-[8-(1-hydroxyethyl)- 6-[6-(methoxy methoxy)-2,7-dimethylindazol-5-yl]-1,5-naphthyridin-2-yl]pip erazine-1- carboxylate (D46, 43 mg). LCMS: (ES, m/z): 563 [M+H] ⁺ Synthesis of Compound 364 A solution of Intermediate D46 (43 mg, 0.076 mmol, 1 equiv) in HCl (gas) in 1,4-dioxane (2 mL) was stirred for 1h at room temperature, and subsequently concentrated under reduced pressure. The residue was purified by Prep-TLC following Condition 1, Gradient 1 as previously delineated to afford 5-[4-(1-hydroxyethyl)-6-(piperazin-1-yl)-1,5-naphthyridin-2- yl]-2,7- dimethylindaz ol-6-ol (Compound 364, 17 mg). LCMS: (ES, m/z): 419 [M+H] ⁺ . ¹ H NMR: (300 MHz, DMSO-d ₆ ) δ 8.4λ (s, 1H), 8.3λ (d, J = 7.4 Hz, 2H), 8.27 (d, J = 9.3 Hz, 1H), 7.60 (d, J = 9.4 Hz, 1H), 5.65 (q, J = 6.4 Hz, 1H), 4.15 (s, 3H), 3.98 (q, J = 3.9 Hz, 4H), 3.28 (s, 4H), 2.39 (s, 3H), 1.54 (dd, J = 6.7, 2.4 Hz, 3H). Example 210: Synthesis of Compound 487 Synthesis of Intermediate D48 To a solution of tert-butyl N-[1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3-yl]-N-[(1r ,3r) -3- fluorocyclobutyl]carbamate (D47,70 mg, 0.166 mmol, 1 equiv) and 4-fluoro-5- (methoxymethoxy)-2-methyl-6- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazol e (112.14 mg, 0.332 mmol, 2 equiv) in 1,4-dioxane (1 mL)and H ₂ O (0.25 mL) were added K ₂ CO ₃ (68.95 mg, 0.498 mmol, 3 equiv) and Pd(dppf)Cl ₂ (12.17 mg, 0.017 mmol, 0.1 equiv). After stirring for 5 h at 80°C under a nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure. The residue was purified by Prep-TLC/silica gel column chromatography and eluted with CH ₂ Cl ₂ /MeOH (9:1) to afford tert-butyl N-(1-{6-[4-fluoro-5- (methoxymethoxy) -2-methyl-1,3-benzoxazol-6-yl]-1,5-naphthyridin-2-yl}pyrroli din-3-yl)-N- [(1r,3r)-3-fluorocyclobutyl]carbamate (D48, 30 mg). Synthesis of Compound 487 TFA (0.2 mL) was added to a solution of Intermediate D48 (30 mg, 0.050 mmol, 1 equiv) in DCM (1 mL). After stirring for 1 h at room temperature under a nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure. The crude product was purified by Chiral-Prep-HPLC following Condition 12, Gradient 1 as previously described to afford 4- fluoro-2-methyl-6-[6-(3-{[(1r,3r)-3-fluorocyclobutyl] amino}pyrrolidin-1-yl) -1,5-naphthyridin- 2-yl]-1,3-benzoxazol-5-ol (Compound 487, 1.6 mg). Absolute stereochemistry of the compound was arbitrarily assigned LCMS: (ES, m/z): 452 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 15.06 (s, 1H), 8.45 (d, J = 9.2 Hz, 1H), 8.33 (d, J = 1.4 Hz, 1H), 8.14 (dd, J = 22.9, 9.2 Hz, 2H), 7.19 (d, J = 9.3 Hz, 1H), 5.19 (dtt, J = 56.9, 6.5, 3.6 Hz, 1H), 3.72 (s, 2H), 3.55 (s, 2H), 3.34 – 3.37(m, 1H) 2.64 (s, 3H), 2.34 – 2.43(m, 3H), 2.14 – 2.29 (m, 3H), 1.87 (d, J = 31.1 Hz, 1H). Example 211: Synthesis of Compounds 488 and 489 Synthesis of Intermediate D50 A solution of 1-(6-chloro-1,5-naphthyridin-2-yl)-N-[1-(fluoromethyl)cyclop ropyl]pyrrolidin-3- amine (D49, 300 mg, 0.935 mmol, 1 equiv) and K ₃ PO ₄ (595.51 mg, 2.805 mmol, 3 equiv) in dioxane (6 mL) and H ₂ O (1.2 mL) was treated with Pd(dppf)Cl ₂ (68.43 mg, 0.094 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere followed by the addition of 5- (methoxymethoxy)-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)-1,3-benzoxazole (358.16 mg, 1.122 mmol, 1.2 equiv) at room temperature. The reaction was stirred for 2 h at 80 °C, later allowed to cool to room temperature and concentrated under vacuum. The residue was purified by silica gel column chromatography and eluted with CH ₂ Cl ₂ / MeOH (1:1) to afford N-[1-(fluoromethyl)cyclopropyl]-1-{6-[5-(methoxymethoxy)-2-m ethyl-1,3-benzoxazol-6- yl]-1,5-naphthyridin-2-yl}pyrrolidin-3-amine (D50, 170 mg). Synthesis of Compounds 488 and 489 A mixture of Intermediate D50 (170 mg, 0.356 mmol, 1 equiv) and HCl(gas)in 1,4-dioxane (2 mL, 65.826 mmol, 184.91 equiv) in methanol (2 mL, 0.062 mmol, 0.18 equiv) was stirred for 2 h at room temperature under nitrogen atmosphere. The residue product was purified by reverse phase flash chromatography following Condition 5, Gradient 5 to afford 70 mg of solid that was subsequently concentrated under vacuum. The crude product was purified by prep-CHIRAL- HPLC following Condition 13, Gradient 1 to afford 6-{6-[(3R)-3-{[1- (fluoromethyl)cyclopropyl]amino}pyrrolidin-1-yl]-1,5-naphthy ridin-2-yl}-2-methyl-1,3- benzoxazol-5-ol (Compound 488, 9.5 mg) and 6-{6-[(3S)-3-{[1- (fluoromethyl)cyclopropyl]amino}pyrrolidin-1-yl]-1,5-naphthy ridin-2-yl}-2-methyl-1,3- benzoxazol-5-ol (Compound 489, 9.5 mg). Absolute stereochemistry of the compunds was assigned arbitrarily. The first resolved peak was Compound 488: LCMS: (ES, m/z): 434 [M+H] +. ¹ H NMRμ (400 MHz, DMSO-d6) δ 14.52 (s, 1H), 8.45 – 8.3λ (m, 2H), 8.10 (dd, J = 13.8, λ.2 Hz, 2H), 7.15 (d, J = λ.3 Hz, 1H), 7.12 (s, 1H), 4.47 (s, 1H), 4.35 (s, 1H), 3.77 (s, 1H), 3.70 (s, 2H), 3.54 (d, J = 8.λ Hz, 1H), 3.32 (d, J = 1.4 Hz, 1H), 2.84 – 2.64 (m, 1H), 2.61 (d, J = 1.6 Hz, 3H), 2.14 (s, 1H), 1.λ1 (s, 1H), 0.62 (s, 4H). The second resolved peak was Compound 489μ LCMS: (ES, m/z): 434 [M+H] +. ¹ H NMRμ (400 MHz, DMSO-d6) δ 14.52 (s, 1H), 8.45 – 8.38 (m, 2H), 8.10 (dd, J = 13.5, λ.3 Hz, 2H), 7.15 (d, J = λ.3 Hz, 1H), 7.12 (s, 1H), 4.47 (s, 1H), 4.34 (s, 1H), 3.81 – 3.70 (m, 1H), 3.68 (s, 2H), 3.54 (d, J = λ.4 Hz, 1H), 3.32 (d, J = 1.4 Hz, 1H),2.71 (s, 1H), 2.61 (s, 3H), 2.14 (dd, J = 12.5, 6.4 Hz, 1H), 1.λ1 (s, 1H), 0.62 (s, 4H). Example 212: Synthesis of Compounds 490, 365, 366, and 367 Synthesis of Intermediate D52 Into a 250 mL round-bottom flask were added tert-butyl 4-oxopiperidine-1-carboxylate (D51, 8 g, 40.151 mmol, 1 equiv), DMF-DMA (1.39 g, 60.227 mmol, 1.5 equiv) and DMF (80 mL). The mixture was stirred for 1.2 h at 110 °C, quenched by the addition of water (100 mL) at room temperature, and the aqueous layer was extracted with EtOAc(20 ml x 3). The organic layers were washed with brine (20 ml x1), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure to afford tert-butyl (3E)-3-[(dimethylamino)methylidene]- 4-oxopiperidine -1-carboxylate (D52, 10 g). Synthesis of Intermediate D53 Into a 250 mL sealed tube were added Intermediate D52, (9 g, 35.387 mmol, 1 equiv), hydrazine hydrate (1.97 g, 39.319 mmol, 1 equiv) and EtOH (100 mL). The mixture was stirred for 6h at 80°C, quenched by the addition of water (100 mL), and concentrated under reduced pressure. The aqueous layer was extracted with EtOAc (3x25 mL), and the combined organic layers were concentrated under reduced pressure. The residue was purified by reverse flash chromatography following Condition 3, Gradient 3 as delineated previously to afford tert-butyl 2H,4H,6H,7H- pyrazolo[4,3-c]pyridine-5-carboxylate (D53, 8 g) Synthesis of Intermediates D54 and D55 A solution of Intermediate D53 (8 g, 35.830 mmol, 1 equiv) in THF (80 mL) was treated with NaH (1.03 g, 42.996 mmol, 1.2 equiv) for 10 min at 0°C under nitrogen atmosphere, then MeI (6.10 g, 42.996 mmol, 1.2 equiv) was added at room temperature, and the mixture was stirred for 12 h at room temperature, and later quenched by the addition of water (100 mL) at 0°C. The aqueous layer was extracted with EtOAc (3x50 mL), and the combined organic layers were concentrated under reduced pressure. The crude product was purified by Chiral-Prep-HPLC following Condition 8, Gradient 1 as previously described to afford tert-butyl 2-methyl- 4H,6H,7H-pyrazolo[4,3-c]pyridine-5-carboxylate (D54, 1 g) as an oil and tert-butyl 1-methyl- 4H,6H,7H-pyrazolo[4,3-c]pyridine-5-carboxylate (D55, 1.2 g) as an oil. Synthesis of Intermediate D56 A mixture of Intermediate D54 (1 g, 4.214 mmol, 1 equiv) and HCl(gas)in 1,4-dioxane (10 mL) in MeOH (10 mL) was stirred for 2h at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure to afford 2-methyl-4H,5H,6H,7H- pyrazolo[4,3-c]pyridine (D56, 450 mg). Synthesis of Intermediate D57 A mixture of Intermediate D55 (1.2 g, 5.057 mmol, 1 equiv) and HCl(gas) in 1,4-dioxane (10 mL) in MeOH (10 mL) was stirred for 2h at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure to afford 1-methyl-4H,5H,6H,7H- pyrazolo[4,3-c]pyridine (D57, 600 mg). A solution of Intermediate D56 (45.01 mg, 0.328 mmol, 1 equiv) in 1,4-dioxane (3 mL) was treated with N-tert-butyl-1-(6-chloro-1,5-naphthyridin-2-yl)pyrrolidin-3- amine (100 mg, 0.328 mmol, 1.00 equiv), Cs2CO ₃ (213.78 mg, 0.656 mmol, 2 equiv), SPhos Pd Gen.3 (13.47 mg, 0.033 mmol, 0.1 equiv), and SPhos (13.47 mg, 0.033 mmol, 0.1 equiv) for 3h at 80°C under nitrogen atmosphere. The resulting mixture was filtered, washed with EtOAc (3x10 mL), and the filtrate was concentrated under reduced pressure. The crude product was purified by Chiral-Prep- HPLC following Condition 14, Gradient 1 to afford the diastereomeric mixture N-(tert-butyl)-1- (6-(2-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5- yl)-1,5-naphthyridin-2- yl)pyrrolidin-3-amine. The product was purified by Chiral-Prep-HPLC with the following following Condition 4, Gradient 8 as previously delineated to afford (3R)-N-tert-butyl-1-(6-{2- methyl-4H,6H,7H-pyrazolo[4,3-c]pyridin-5-yl} -1,5-naphthyridin-2-yl)pyrrolidin-3-amine (Compound 490, 1.9 mg) and (3S)-N-tert-butyl-1-(6-{2-methyl-4H,6H,7H-pyrazolo[4,3- c]pyridin-5-yl}-1,5-naphthyridin-2-yl)pyrrolidin-3-amine (Compound 366, 1.6 mg). Absolute stereochemistry of the compounds was assigned arbitrarily. Compound 490 was resolved from the first peak. LCMS: (ES, m/z): 406[M+H] +. ¹ H NMR: (400 MHz, DMSO-d6) δ 7.77 – 7.68 (m, 2H), 7.49 (s, 1H), 7.31 (d, J = 9.3 Hz, 1H), 6.88 (d, J = 9.2 Hz, 1H), 4.62 (s, 2H), 3.92 (t, J = 5.9 Hz, 2H), 3.75 (s, 3H), 3.59 (s, 2H), 3.48 (s, 2H), 3.02 (s, 2H), 2.71 (t, J = 5.8 Hz, 2H), 2.14 (s, 1H), 1.70 (d, J = 9.7 Hz, 1H), 1.08 (s, 9H). Compound 366 was resolved from the second peak. LCMS: (ES, m/z): 406[M+H] +. ¹ H NMR: (400 MHz, DMSO-d6) δ 7.73 (dd, J = 9.1, 6.3 Hz, 2H), 7.49 (s, 1H), 7.31 (d, J = 9.4 Hz, 1H), 6.88 (d, J = 9.2 Hz, 1H), 4.62 (s, 2H), 3.92 (t, J = 5.8 Hz, 2H), 3.75 (s, 3H), 3.59 (t, J = 8.2 Hz, 2H), 3.49 (s, 2H), 3.03 (s, 1H), 2.71 (t, J = 5.8 Hz, 1H), 2.14 (s,2H), 1.72 (s, 1H), 1.24 (s, 1H), 1.08 (s, 9H). Synthesis of Compounds 365 and 367 A solution of 1-methyl-4H,5H,6H,7H-pyrazolo[4,3-c]pyridine (D57, 45.01 mg, 0.328 mmol, 1 equiv) in 1,4-dioxane (3 mL) was treated with N-tert-butyl-1-(6-chloro-1,5-naphthyridin-2- yl)pyrrolidin-3-amine (100 mg, 0.328 mmol, 1.00 equiv), Cs ₂ CO ₃ (213.78 mg, 0.656 mmol, 2 equiv), SPhos Pd Gen.3 (13.47 mg, 0.033 mmol, 0.1 equiv), and SPhos (13.47 mg, 0.033 mmol, 0.1 equiv) for 3h at 80°C under nitrogen atmosphere. The resulting mixture was filtered, washed with EtOAc (3x10 mL), and the filtrate was concentrated under reduced pressure. The crude product was purified by Chiral-Prep-HPLC following Condition 14, Gradient 1 as previously described. The product was purified by Chiral-Prep-HPLC following Condition 4, Gradient 8 as previously delineated to afford (3S)-N-tert-butyl-1-(6-{1-methyl-4H,6H,7H-pyrazolo[4,3- c]pyridin-5-yl} -1,5-naphthyridin-2-yl)pyrrolidin-3-amine ( Compound 365, 1.5 mg) and (3R)- N-tert-butyl-1-(6-{1-methyl -4H,6H,7H-pyrazolo[4,3-c]pyridin-5-yl}-1,5-naphthyridin-2- yl)pyrrolidin-3-amine (Compound 367, 1.6 mg). Absolute stereochemistry was assigned arbitrarily. Compound 365 was resolved from the first peak. LCMS: (ES, m/z): 406[M+H] +. ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 7.73 (ddd, J = 9.1, 5.0, 0.8 Hz, 2H), 7.33 (d, J = 9.3 Hz, 1H), 7.28 (s, 1H), 6.88 (d, J = 9.2 Hz, 1H), 4.59 (s, 2H), 3.94 (t, J = 5.7 Hz, 2H), 3.76 (dd, J = 10.0, 6.9 Hz, 1H), 3.67 (s, 3H), 3.60 (d, J = 8.2 Hz, 1H), 3.48 (t, J = 7.3 Hz, 1H), 3.41 – 3.37 (m, 1H), 3.02 (dd, J = 10.0, 7.3 Hz, 1H), 2.78 (t, J = 5.8 Hz, 2H), 2.13 (d, J = 8.3 Hz, 1H), 1.71 (dd, J = 11.7, 8.4 Hz, 1H), 1.08 (s, 9H). Compound 367 was resolved from the second peak. LCMS: (ES, m/z): 406[M+H] +. ¹ H NMR: (400 MHz, DMSO-d6) δ 7.74 (dd, J = 9.2, 3.0 Hz, 2H), 7.34 (d, J = 9.2 Hz, 1H), 7.28 (s, 1H), 6.89 (d, J = 9.2 Hz, 1H), 4.59 (s, 2H), 3.95 (t, J = 5.7 Hz, 2H), 3.77 (s, 1H), 3.67 (s, 3H), 3.60 (s, 1H), 3.48 (t, J = 7.3 Hz, 1H), 3.41 – 3.37 (m, 2H) ₃ .03 (s, 1H), 2.78 (t, J = 5.8 Hz, 2H), 2.13 (s, 1H), 1.73 (s, 1H), 1.10 (s, 9H). Example 213: Synthesis of Compound 370 Synthesis of Intermediate D59 To a stirred solution of 5-{6-chloropyrido[3,2-d]pyrimidin-2-yl}-6-methoxy-2,7- dimethylindazole (D58, 200 mg, 0.589 mmol, 1 equiv) and tert-butyl 4-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxyla te (200 mg, 0.648 mmol, 1.1 equiv) in dioxane (5 mL) and H ₂ O (0.5 mL) were added K ₂ CO ₃ (203 mg, 1.472 mmol, 2.5 equiv) and Pd(dppf)Cl ₂ (43 mg, 0.059 mmol, 0.1 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 5 h at 80°C under nitrogen atmosphere, and later allowed to cool down to room temperature. The resulting mixture was concentrated under reduced pressure, and the residue was purified by reverse flash chromatography following Condition 10, Gradient 12 as previously delineated to afford tert-butyl 4-[2-(6-methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2-d]pyrimi din-6-yl]-3,6- dihydro-2H-pyridine-1-carboxylate (D59, 87 mg) as a solid. LCMS: (ES, m/z): 487 [M+H] ⁺ . Synthesis of Intermediate D60 To a solution of Intermediate D59 (87 mg, 0.179 mmol, 1 equiv) in EA (5 mL) was added Pd/C (38 mg, 0.358 mmol, 2 equiv) under nitrogen atmosphere in a 25 mL round-bottom flask. The mixture was hydrogenated at room temperature for 8 h under hydrogen atmosphere using a hydrogen balloon, filtered through a Celite pad and concentrated under reduced pressure. The residue was dissolved in DCE (5 mL), and MnO ₂ (151 mg, 1.730 mmol, 10 equiv) was added in portions at room temperature. The resulting mixture was stirred for 4 h at 60°C and subsequently allowed to cool to room temperature. The resulting mixture was filtered, washed with CH ₂ Cl ₂ (3 x 5 mL), and the filtrate was concentrated under reduced pressure to afford tert-butyl 4-[2-(6- methoxy-2,7-dimethylindazol-5-yl)pyrido[3,2-d]pyrimidin-6-yl ]piperidine-1-carboxylate (D60, 84 mg). LCMS: (ES, m/z): 489 [M+H] ⁺ . Synthesis of Compound 370 To a stirred solution of Intermediate D60 (82 mg, 0.168 mmol, 1 equiv) in DCE (5 mL) was added boron tribromide (420 mg, 1.680 mmol, 10 equiv) dropwise at room temperature. The resulting mixture was stirred for 0.5 h at 80°C, later allowed to cool to room temperature, quenched by the addition of MeOH (5 mL) at room temperature, and finally concentrated under vacuum. The residue was purified by reverse flash chromatography following Condition 10, Gradient 13 as previously described to afford 2,7-dimethyl-5-[6-(piperidin-4-yl)pyrido[3,2- d]pyrimidin-2-yl]indazol-6-ol (Compound 370, 16 mg) as a solid. LCMS: (ES, m/z): 375 [M+H] ⁺ . ¹ H NMR: (300 MHz, DMSO-d6) δ 13.23 (s, 1H), λ.71 (d, J = 0.8 Hz, 1H), λ.01 (s, 1H), 8.48 (d, J = 9.4 Hz, 2H), 8.02 (d, J = 8.9 Hz, 1H), 4.16 (s, 3H), 3.11 (s, 1H), 3.05 (d, J = 13.0 Hz, 2H), 2.65 (t, J = 11.8 Hz, 2H), 2.41 (s, 3H), 1.89 (d, J = 12.3 Hz, 2H), 1.83-1.66 (m, 2H). Example 214: Synthesis of Compounds 491 and 373 Synthesis of Intermediates D62 and D63 A solution of 1-(6-chloro-1,5-naphthyridin-2-yl)-N-[1-(fluoromethyl)cyclop ropyl]pyrrolidin-3- amine (D61, 300 mg, 0.935 mmol, 1 equiv) and 4-fluoro-5-(methoxymethoxy)-2-methyl-6- (4,4,5,5-tetramethyl -1,3,2-dioxaborolan-2-yl)-1,3-benzoxazole (378.35 mg, 1.122 mmol, 1.2 equiv) in dioxane (1.2 mL) and H ₂ O (6 mL) was treated with Pd(dtbpf)Cl ₂ (60.95 mg, 0.094 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere followed by the addition of K ₃ PO ₄ (390.56 mg, 2.805 mmol, 3 equiv) in portions at room temperature. The mixture was stirred for 2h at 80°C and later allowed to cool to room temperature. The resulting mixture was concentrated under vacuum, the residue was purified by silica gel column chromatography and eluted with CH ₂ Cl ₂ /MeOH (10:1) to afford the crude diastereomeric mixture 1-{6-[4-fluoro-5- (methoxymethoxy)-2-methyl-1,3-benzoxazol-6-yl]-1,5-naphthyri din-2-yl}-N-[1- (fluoromethyl)cyclopropyl]pyrrolidin-3-amine (200 mg) as a solid. The crude product (200mg) was purified by Prep-CHIRAL-HPLC following Condition 4, Gradient 14 as previously delineated to afford (3R)-1-{6-[4-fluoro-5-(methoxymethoxy)-2-methyl-1,3-benzoxaz ol-6-yl]- 1,5-naphthyridin-2-yl}-N-[1-(fluoromethyl)cyclopropyl]pyrrol idin-3-amine (D62, 60 mg) and (3S)-1-{6-[4-fluoro-5-(methoxymethoxy)-2-methyl-1,3-benzoxaz ol-6-yl]-1,5-naphthyridin-2- yl}-N-[1-(fluoromethyl)cyclopropyl]pyrrolidin-3-amine (D63, 55 mg). Absolute stereochemistry of the compounds was assigned arbitrarily.

Synthesis of Compound 491 A mixture of Intermediate D62 (60 mg, 0.121 mmol, 1 equiv) and HCl(gas)in 1,4-dioxane (1 mL) in MeOH (1 mL) was stirred for 2h at room temperature under nitrogen atmosphere and subsequently concentrated under vacuum. The crude product (55mg) was purified by Prep-HPLC following Condition 1, Gradient 31 as previously described to afford 4-fluoro-6-{6-[(3R)-3-{[1- (fluoromethyl)cyclopropyl]amino}pyrrolidin-1-yl]-1,5-naphthy ridin-2-yl}-2-methyl-1,3- benzoxazol-5-ol (Compound 491, 17.6 mg). Absolute stereochemistry of the compound was assigned arbitrarily. LCMS: (ES, m/z): 452 [M+H] +. ¹ H NMR: (400 MHz, DMSO-d6) δ 15.06 (s, 1H), 8.44 (d, J = 9.2 Hz, 1H), 8.32 (d, J = 1.3 Hz, 1H), 8.13 (ddd, J = 19.0, 9.2, 0.8 Hz, 2H), 7.17 (d, J = 9.3 Hz, 1H), 4.47 (s, 1H), 4.34 (s, 1H), 3.77 (d, J = 9.2 Hz, 1H), 3.70 (s, 2H), 3.54 (d, J = 9.4 Hz, 1H), 3.34 (s, 1H),2.71 (d, J = 4.1 Hz, 1H), 2.64 (s, 3H), 2.14 (dq, J = 12.6, 6.3 Hz, 1H), 1.94 – 1.86 (m, 1H), 0.62 (d, J = 4.6 Hz, 4H). Synthesis of Compound 373 A mixture of Intermediate D63 (55 mg, 0.111 mmol, 1 equiv) and HCl(gas)in 1,4-dioxane (1 mL) in MeOH (1 mL) was stirred for 2h at room temperature under nitrogen atmosphere then concentrated under vacuum. The crude product (50mg) was purified by Prep-HPLC following Condition 1, Gradient 32 as previously described to afford 4-fluoro-6-{6-[(3S)-3-{[1- (fluoromethyl)cyclopropyl]amino}pyrrolidin-1-yl]-1,5-naphthy ridin-2-yl}-2-methyl-1,3- benzoxazol-5-ol (Compound 373, 9.6 mg). Absolute stereochemistry of the compound was assigned arbitrarily. LCMS: (ES, m/z): 452 [M+H] +. ¹ H NMR: (400 MHz, DMSO-d6) δ 15.06 (s, 1H), 8.44 (d, J = 9.2 Hz, 1H), 8.32 (d, J = 1.4 Hz, 1H), 8.13 (dd, J = 19.1, 9.2 Hz, 2H), 7.17 (d, J = 9.3 Hz, 1H), 4.47 (s, 1H), 4.34 (s, 1H), 3.78 (s, 1H), 3.70 (s, 2H), 3.54 (d, J = 9.3 Hz, 1H), 3.31 (s, 1H), 2.71 (d, J = 4.2 Hz, 1H), 2.64 (s, 3H), 2.14 (dt, J = 12.4, 6.3 Hz, 1H), 1.90 (s, 1H), 0.62 (d, J = 4.5 Hz, 4H). Example 215: Synthesis of Compound 400 Synthesis of Intermediate D65 A solution of 2-amino-6-methoxybenzoic acid (D64, 17 g, 101.697 mmol, 1 equiv), Boc ₂ O (23.30 g, 106.782 mmol, 1.05 equiv) and TEA (10.81 g, 106.782 mmol, 1.05 equiv) in ACN (170 mL) was stirred for 16 h at room temperature. The resulting mixture was poured into water (100 mL) and extracted with CH ₂ Cl ₂ (3 x 100 mL). The combined organic layers were washed with brine (2 x 100 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with CH ₂ Cl ₂ / MeOH (1% TEA) (10:1) to afford 2-[(tert-butoxycarbonyl)amino]-6-methoxybenzoic acid (D65, 25 g). LCMS: (ES, m/z):268 [M+H] ⁺ . Synthesis of Intermediate D66 To a stirred solution of Intermediate D65 (21 g, 78.569 mmol, 1 equiv) in ACN (80 mL) was added NBS (13.98 g, 78.569 mmol, 1 equiv) dropwise at 0 °C. The resulting mixture was stirred for 4 h at room temperature, subsequently basified to pH 8 with saturated NaHCO ₃ (aq.), and later extracted with EtOAc (2 x 500 mL). The combined organic layers were washed with brine (2 x 500 mL), dried over anhydrous Na ₂ SO ₄ and the filtrate was concentrated under reduced pressure. The crude product was re-crystallized from DCM/PE (1:5100 mL) to afford 3-bromo- 6-[(tert-butoxycarbonyl)amino]-2-methoxybenzoic acid (D66, 9 g). LCMS: (ES, m/z):346/348 [M+H] ⁺ . Synthesis of Intermediate D67 A solution of Intermediate D66 (10 g, 28.887 mmol, 1 equiv) in HCl(gas)in 1,4-dioxane (10 mL) was stirred for 1 h at room temperature and later concentrated under vacuum. The residue was basified to pH 8 with saturated NaHCO ₃ (aq.), extracted with CH ₂ Cl ₂ (2 x 20 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. BH ₃ . THF (4.97 g, 57.774 mmol, 2 equiv) was added dropwise to the mixture in THF (10 mL) and allowed to stir overnight at room temperature. The resulting mixture was diluted with MeOH (20 mL) and (1M) HCl and extracted with EtOAc (2 x 50 mL). The combined organic layers were washed with brine (2 x 50 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford (6-amino-3-bromo-2-methoxyphenyl)methanol (D67, 5 g). LCMS: (ES, m/z):232/234 [M+H] ⁺ . Synthesis of Intermediate D68 A mixture of Intermediate D67 (5 g, 21.545 mmol, 1 equiv) and MnO ₂ (9.36 g, 107.725 mmol, 5 equiv) in CHCl ₃ (50 mL) was stirred for 6 h by reflux and later allowed to cool to room temperature. The resulting mixture was filtered, the filter cake was washed with DCM (2 x 30 mL), and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (10:1) to afford 6-amino-3-bromo-2- methoxybenzaldehyde (D68, 4 g). LCMS: (ES, m/z):230/232 [M+H] ⁺ . Synthesis of Intermediate D69 A mixture of Intermediate D68 (4 g, 17.387 mmol, 1 equiv) and ethyl 3-(triphenyl-lambda5- phosphanylidene)propanoate (6.93 g, 19.126 mmol, 1.1 equiv) in toluene (40 mL) was stirred overnight at room temperature and subsequently concentrated under vacuum. The residue was purified by silica gel column chromatography and eluted with PE / EA (5:1) to afford ethyl (2E)- 3-(6-amino-3-bromo-2-methoxyphenyl)prop-2-enoate (D69, 4 g). LCMS: (ES, m/z):300/302 [M+H] ⁺ . Synthesis of Intermediate D70 A solution of Intermediate D69 (3.5 g, 11.661 mmol, 1 equiv) and LiOH(2M) (29 mL, 58.305 mmol, 5 equiv) in THF (70 mL) was stirred overnight at room temperature and then acidified to pH 5 with HCl (1M). The resulting mixture was extracted with EtOAc (3 x 200 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure to afford (2E)-3-(6- amino-3-bromo-2-methoxyphenyl)prop-2-enoic acid (D70, 3 g, 94.55%). LCMS: (ES, m/z):272/274 [M+H] ⁺ . Synthesis of Intermediate D71 A solution of Intermediate D70 (3 g, 11.025 mmol, 1 equiv) and HCl (15 mL) in IPA (30 mL) was stirred overnight by reflux and later allowed to cool to room temperature. The mixture was then neutralized to pH 7 with saturated NaHCO ₃ (aq.), extracted with EtOAc (3 x 200 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure to afford 6- bromo-5-methoxy-1H-quinolin-2-one (D71, 1.5 g). LCMS: (ES, m/z):254/256 [M+H] ⁺ . Synthesis of Intermediate D72 To a stirred mixture of Intermediate D71 (1 g, 3.936 mmol, 1 equiv) and Cs2CO ₃ (2.56 g, 7.872 mmol, 2 equiv) in ACN (20 mL) was added 4-methoxybenzyl chloride (0.92 g, 5.904 mmol, 1.5 equiv) dropwise at 0 °C. The resulting mixture was stirred for 12 h at room temperature and then poured into water (100 mL). The resulting mixture was extracted with EtOAc (2 x 100 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (5:1) to afford 6-bromo-5-methoxy-1-[(4-methoxyphenyl)methyl]quinolin-2-one (D72, 1 g). LCMS: (ES, m/z):374/376 [M+H] ⁺ .

Synthesis of Intermediate D73 A solution of Intermediate D72 (1 g, 2.672 mmol, 1 equiv), bis(pinacolato)diboron (1.02 g, 4.008 ^{mmol, 1.5 equiv), Pd(dppf)Cl} 2 ^.CH 2 ^Cl 2 ^{(0.22 g, 0.267 mmol, 0.1 equiv) and AcOK (0.79 g, 8.050} mmol, 3.01 equiv) in dioxane (20 mL) was stirred for 3 h at 100 °C under nitrogen atmosphere and subsequently allowed to cool to room temperature. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford 5-methoxy-1-[(4- methoxyphenyl)methyl]-6-(4,4,5,5-tetramethyl-1,3,2-dioxaboro lan-2-yl)quinolin-2-one (D73, 760 mg). LCMS: (ES, m/z):422 [M+H] ⁺ . Synthesis of Intermediate D74 A solution of Intermediate D73 (760 mg, 1.804 mmol, 1 equiv), 5-bromo-2-methylpyrazolo[3,4- c]pyridine (382.53 mg, 1.804 mmol, 1 equiv), RuPhos Palladacycle Gen.3 (42.09 mg, 0.090 mmol, 0.05 equiv), RuPhos (84.18 mg, 0.180 mmol, 0.1 equiv) and K3PO4 (1148.74 mg, 5.412 mmol, 3 equiv) in dioxane (5 mL) and H ₂ O (1 mL) was stirred for 16 h at 80 °C under nitrogen atmosphere. The resulting mixture was extracted with EtOAc (2 x 50 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford 5-methoxy-1-[(4- methoxyphenyl)methyl]-6-{2-methylpyrazolo[3,4-c]pyridin-5-yl }quinolin-2-one (D74, 200 mg). LCMS: (ES, m/z):427 [M+H] ⁺ . Synthesis of Intermediate D75 A solution of Intermediate D74 (200 mg, 0.469 mmol, 1 equiv) in POCl ₃ (20 mL) was stirred for 1 h at 100 °C and later allowed to cool to room temperature and subsequently concentrated under vacuum. The mixture was basified to pH 8 with saturated NaHCO ₃ (aq.), and the residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford 2-chloro-5- methoxy-6-{2-methylpyrazolo[3,4-c]pyridin-5-yl}quinoline (D75, 100 mg). LCMS: (ES, m/z):325 [M+H] ⁺ . Synthesis of Intermediate D76 A solution of Intermediate D75 (80 mg, 0.246 mmol, 1 equiv), tert-butyl 4-iodopiperidine-1- carboxylate (153.30 mg, 0.492 mmol, 2 equiv), pyridine-2-carboximidamide hydrochloride (38.82 mg, 0.246 mmol, 1 equiv), NiCl ₂ (31.92 mg, 0.246 mmol, 1 equiv). TBAI (90.99 mg, 0.246 mmol, 1 equiv) and Mn (40.60 mg, 0.738 mmol, 3 equiv) in DMA (1.6 mL) was stirred for 16 h at 80 °C under nitrogen atmosphere and subsequently allowed to cool to room temperature. The resulting mixture was extracted with EtOAc (2 x 50 mL). The combined organic layers were washed with brine (2 x 50 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford tert-butyl 4-(5-methoxy-6-{2-methylpyrazolo[3,4-c]pyridin- 5-yl}quinolin-2-yl)piperidine-1-carboxylate (D76, 20 mg). LCMS: (ES, m/z):474 [M+H] ⁺ . Synthesis of Compound 400 To a stirred solution of Intermediate D76 (15 mg, 0.032 mmol, 1 equiv) in DCM (1.5 mL) was added BBr3 (39.67 mg, 0.160 mmol, 5 equiv) dropwise at 0 °C and allowed to stir for 72 h at room temperature. The resulting mixture was then diluted with MeOH (10 mL) and concentrated under vacuum. The mixture/residue was basified to pH 8 with saturated NaHCO ₃ (aq), extracted with CH ₂ Cl ₂ (2 x 10 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The crude product was purified by Chiral-Prep-HPLC following Condition 9, Gradient 2 as previously described to afford 6-{2-methylpyrazolo[3,4-c]pyridin-5-yl}-2- (piperidin-4-yl)quinolin-5-ol (Compound 400, 2.5 mg). LCMS: (ES, m/z):360 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d6) δ 15.66 (s, 1H), λ.37 (t, J = 1.2 Hz, 1H), 8.68 (s, 1H), 8.62 – 8.54 (m, 2H), 8.32 (d, J = 9.2 Hz, 1H), 7.49 – 7.40 (m, 2H), 4.34 (s, 3H), 3.09 (d, J = 12.0 Hz, 2H), 3.00 – 2.90 (m, 1H), 2.69 – 2.64 (m, 2H), 1.85 (d, J = 12.6 Hz, 2H), 1.75 (tt, J = 12.2, 6.2 Hz, 2H). Example 216: Synthesis of Compound 403 Synthesis of Intermediate D78 To a stirred solution of 5-bromo-6-methoxy-2-methylindazole-7-carbonitrile (589 mg, 2.212 mmol, 1 equiv) and 4,4,5,5-tetramethyl-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)- 1,3,2- dioxaborolane (674 mg, 2.654 mmol, 1.2 equiv) in dioxane (20 mL) were added KOAc (434 mg, 4.424 mmol, 2 equiv) and Pd(dppf)Cl ₂ (162 mg, 0.221 mmol, 0.1 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 90°C under nitrogen atmosphere and allowed to cool down to room temperature. To the above mixture was added 2-bromopyrido[3,2-d]pyrimidin-6-ol (D77, 500 mg, 2.212 mmol, 1 equiv), Pd(dppf)Cl ₂ (162 mg, 0.221 mmol, 0.1 equiv), K3PO4 (939 mg, 4.424 mmol, 2 equiv) and H ₂ O (2 mL) in portions at room temperature and subsequently stirred for an additional 3 h at 90°C, later allowed to cool room temperature, and finally concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with CH ₂ Cl ₂ / MeOH (10:1) to afford 5-{6-hydroxypyrido[3,2-d]pyrimidin-2-yl}-6-methoxy-2-methyli ndazole-7-carbonitrile (D78, 110 mg). LCMS: (ES, m/z): 333 [M+H] ⁺ . Synthesis of Intermediate D79 To a stirred solution of Intermediate D78 (110 mg, 0.331 mmol, 1 equiv) in MeCN (5 mL) was added POCl ₃ (508 mg, 3.310 mmol, 10 equiv) dropwise at room temperature. The resulting mixture was stirred for 3 h at 80°C, then allowed to cool to room temperature and concentrated under vacuum. The residue was dissolved in EtOAc (20 mL), basified to pH 8 with saturated NaHCO ₃ (aq.), and extracted with EtOAc (3x10 mL). The combined organic layers were washed with brine (1x20 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:10) to afford 5-{6-chloropyrido[3,2-d]pyrimidin-2-yl}-6-methoxy-2-methylin dazole- 7-carbonitrile (D79, 56 mg). LCMS: (ES, m/z): 351 [M+H] ⁺ . Synthesis of Intermediate D80 To a stirred solution of Intermediate D79 (55 mg, 0.157 mmol, 1 equiv) and tert-butyl 4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine -1-carboxylate (58 mg, 0.188 mmol, 1.2 equiv) in dioxane (2 mL) and H ₂ O (0.2 mL) were added K ₂ CO ₃ (54 mg, 0.393 mmol, 2.5 equiv) and Pd(dppf)Cl ₂ (12 mg, 0.016 mmol, 0.1 equiv) in portions at room temperature under nitrogen atmosphere, subsequently stirred for 4 h at 90°C under nitrogen atmosphere, and later allowed to cool to room temperature. The reaction was quenched by the addition of water (20 mL) at room temperature and extracted with EtOAc (3x5 mL). The combined organic layers were washed with brine (3x10 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:10) to afford tert-butyl 4-[2-(7-cyano-6-methoxy-2- methylindazol-5-yl)pyrido[3,2-d]pyrimidin-6-yl]-3,6-dihydro- 2H-pyridine-1-carboxylate (D80, 58 mg). LCMS: (ES, m/z): 498 [M+H] ⁺ . Synthesis of Intermediate D81 To a solution of Intermediate D80 (51 mg, 0.103 mmol, 1 equiv) in MeOH (5 mL) was added Pd/C (55 mg, 0.515 mmol, 5 equiv) under nitrogen atmosphere. The mixture was hydrogenated at room temperature for 5 h under hydrogen atmosphere using a hydrogen balloon, filtered through a Celite pad and concentrated under reduced pressure. The residue was diluted with DCE (5 mL), and MnO ₂ (89 mg, 1.030 mmol, 10 equiv) was added in portions at room temperature. The resulting mixture was stirred for an additional 4 h at 60°C and then allowed to cool to room temperature. The resulting mixture was filtered; the filter cake was washed with DCE (3x10 mL), and the filtrate was concentrated under reduced pressure to afford tert-butyl 4- [2-(7-cyano-6-methoxy-2-methylindazol-5-yl)pyrido[3,2-d]pyri midin-6-yl]piperidine-1- carboxylate (D81, 50 mg). LCMS: (ES, m/z): 500 [M+H] ⁺ . Synthesis of Compound 403

To a stirred solution of Intermediate D81 (60 mg, 0.12 mmol, 1 equiv) in DCE (5 mL) was added BBr3 (301 mg, 1.2 mmol, 10 equiv) dropwise at room temperature. The resulting mixture was stirred for 0.5 h at 80°C, subsequently allowed to cool to room temperature, and finally concentrated under vacuum. The residue was purified by reverse flash chromatography following Condition 4, Gradient 3 as previously described to afford 6-hydroxy-2-methyl-5-[6-(piperidin-4- yl)pyrido[3,2-d]pyrimidin-2-yl]indazole-7-carbonitrile; trifluoroacetic acid (Compound 403, 13 mg). LCMS: (ES, m/z): 386 [M+H] ⁺ . ¹ H NMR: (300 MHz, Methanol-d4) δ λ.67 (s, 1H), λ.46 (s, 1H), 8.54-8.42 (m, 2H), 8.02 (d, J = 8.8 Hz, 1H), 4.23 (s, 3H), 3.62 (d, J = 12.9 Hz, 2H), 3.45 (s, 1H), 3.26 (d, J = 12.8 Hz, 2H), 2.43-2.19 (m, 4H). Example 217: Synthesis of Compounds 404 and 405 Synthesis of Intermediate D83 Into a 40mL vial were added 2-bromopyrido[3,2-d]pyrimidin-6-ol (D82, 250 mg, 1.106 mmol, 1 equiv), dioxane (12.5 mL, 147.550 mmol, 133.40 equiv), N-tert-butylpyrrolidin-3-amine (173.06 mg, 1.217 mmol, 1.1 equiv), Cs2CO ₃ (1081.10 mg, 3.318 mmol, 3 equiv), Pd-PEPPSI-IPentCl 2- methylpyridine (o-picoline (93.04 mg, 0.111 mmol, 0.1 equiv) at room temperature. The resulting mixture was stirred for 3h at 100°C under nitrogen atmosphere and subsequently allowed to cool to room temperature. The reaction was quenched by the addition of water (20 mL) at room temperature and extracted with CH ₂ Cl ₂ (3 x 15mL). The combined organic layers were washed with brine (1x20 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The crude product (D83) was used in the next step directly without further purification. LCMS: (ES, m/z):288 [M+H] ⁺ . Synthesis of Intermediate D84 Into a 20 mL vial were added 2-[3-(tert-butylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyrimidin -6-ol (D83,130 mg, 0.452 mmol, 1 equiv) and POCl ₃ (2.60 mL, 69.680 mmol, 154.16 equiv) at room temperature, which was stirred for 2h at 80°C then allowed to cool to room temperature. The resulting mixture was concentrated under reduced pressure. The crude product (D84) was used in the next step directly without further purification. LCMS: (ES, m/z):306 [M+H] ⁺ . Synthesis of Intermediate D85 Into a 20mL vial were added N-tert-butyl-1-{6-chloropyrido[3,2-d]pyrimidin-2-yl}pyrrolid in-3- amine (D84, 180 mg, 0.589 mmol, 1 equiv), 6-(methoxymethoxy)-2-methyl-5-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan -2-yl)indazole (187.28 mg, 0.589 mmol, 1 equiv), dioxane (4 mL, 106.309 mmol, 180.49 equiv), K3PO4 (374.82 mg, 1.767 mmol, 3 equiv) in H ₂ O (0.8 mL) and Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (47.95 mg, 0.059 mmol, 0.1 equiv) at room temperature. The resulting mixture was stirred for 4 h at 90°C under nitrogen atmosphere and later allowed to cool to room temperature. The reaction was quenched by the addition of water (20mL) at room temperature and extracted with EtOAc (3 x 10mL). The combined organic layers were washed with brine (1x10 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with CH ₂ Cl ₂ /MeOH (10:1) to afford crude N-tert-butyl-1-{6-[6-(methoxymethoxy)-2-methylindazol- 5-yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin-3-amine (D85, 70 mg). LCMS: (ES, m/z):462 [M+H] ⁺ . Synthesis of Compound 404 Into a 25mL vial were added Intermediate D85 (60 mg, 0.130 mmol, 1 equiv) and HCl(gas)in 1,4-dioxane (3 mL) and MeOH(3 mL) at room temperature. The resulting mixture was stirred for 1h at room temperature and subsequently concentrated under reduced pressure. The crude product (60 mg) was purified by Prep-HPLC following Condition 16, Gradient 1 as previously described to afford 5-{2-[3-(tert-butylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyrimi din-6-yl}-2- methylindazol-6-ol (Compound 404, 4.6 mg). LCMS: (ES, m/z):418 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 12.68 (s, 1H), λ.23 (d, J = 0.8 Hz, 1H), 8.49 – 8.42 (m, 2H), 8.29 (s, 1H), 8.00 (d, J = 9.2 Hz, 1H), 6.90 (s, 1H), 4.11 (s, 3H), 3.94 (dd, J = 11.2, 6.8 Hz, 1H), 3.79 (ddd, J = 11.9, 8.3, 3.8 Hz, 1H), 3.55 (dq, J = 14.8, 7.5 Hz, 2H), 3.20 (dd, J = 11.2, 7.1 Hz, 1H), 2.17 (dd, J = 10.9, 6.8 Hz, 1H), 1.76 (dq, J = 12.3, 8.7 Hz, 1H), 1.54 (s, 1H), 1.10 (s, 9H). Synthesis of Compound 405 Into a 40 mL vial were added Intermediate D83 (40 mg, 0.139 mmol, 1 equiv), PyBrOP (97.34 mg, 0.209 mmol, 1.5 equiv), K ₂ CO ₃ (57.71 mg, 0.417 mmol, 3 equiv), Et3N (42.26 mg, 0.417 mmol, 3 equiv) and dioxane (3 mL) at room temperature and stirred for 4h at 100°C under nitrogen atmosphere.6-methoxypyridazin-4-ylboronic acid (42.85 mg, 0.278 mmol, 2 equiv) in dioxane (2 mL), Pd(dppf)Cl ₂ CH ₂ Cl ₂ (11.34 mg, 0.014 mmol, 0.1 equiv) and H ₂ O (0.25 mL, 13.877 mmol, 99.70 equiv) was added to the reaction system at 100 °C under nitrogen atmosphere. The resulting mixture was stirred for 6h at 100 °C under nitrogen atmosphere and subsequently allowed to cool down to room temperature. The reaction was quenched by the addition of water (5 mL) at room temperature and extracted with CH ₂ Cl ₂ (3 x 5 mL). The combined organic layers were washed with brine (1x5 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by Prep-TLC (CH ₂ Cl ₂ / MeOH 10:1) to afford the crude product. The crude product (30 mg) was purified by Prep-HPLC following Condition 16, Gradient 1 as previously delineated to afford N-tert-butyl-1- [6-(6-methoxypyridazin-4-yl)pyrido[3,2-d]pyrimidin-2-yl] pyrrolidin-3-amine (Compound 405, 8.7 mg). LCMS: (ES, m/z):380 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d6) δ λ.68 (d, J = 1.8 Hz, 1H), 9.34 (s, 1H), 8.49 (d, J = 9.0 Hz, 1H), 8.06 (d, J = 8.9 Hz, 1H), 7.86 (d, J = 1.8 Hz, 1H), 4.11 (s, 3H), 3.94 (dt, J = 27.9, 10.0 Hz, 1H), 3.78 (d, J = 28.1 Hz, 1H), 3.54 (s, 2H), 3.20 (s, 1H), 2.16 (s, 1H), 1.83 – 1.71 (m, 2H), 1.08 (s, 9H). Example 218: Synthesis of Compound 449 Synthesis of Intermediate D87 A solution of 6-chloro-1,7-naphthyridin-2-ol (D86, 500 mg, 2.769 mmol, 1 equiv) in 1,4-dioxane (10 mL) was treated with N-tert-butylpyrrolidin-3-amine (393.84 mg, 2.769 mmol, 1 equiv) and Pd-PEPPSI-IPentCl 2-methylpyridine (o-picoline (232.89 mg, 0.277 mmol, 0.1 equiv), and Cs ₂ CO ₃ (2706.29 mg, 8.307 mmol, 3 equiv) for 3 h at 80 °C under nitrogen atmosphere. The reaction was quenched by the addition of water (10 mL) and then extracted with EtOAc (3 x 5 mL). The combined organic layers were dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with CHCl ₃ /MeOH (9:1) to afford 6-[3-(tert-butylamino)pyrrolidin - 1-yl]-1,7-naphthyridin-2-ol (D87, 400 mg, 50.45%). A solution of Intermediate D87 (400 mg, 1.397 mmol, 1 equiv) in 1,4-dioxane (10 mL) was treated with PyBrOP (976.72 mg, 2.095 mmol, 1.5 equiv), and triethylamine (424.01 mg, 4.191 mmol, 3 equiv) for 12 h at 100°C under nitrogen atmosphere. Then a solution of 6- (methoxymethoxy)-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)indazole (444.42 mg, 1.397 mmol, 1 equiv) and Pd(dppf)Cl ₂ (113.78 mg, 0.140 mmol, 0.1 equiv) in dioxane (4 mL) and H ₂ O (100 uL) were added to the reaction system. The resulting mixture was stirred for 4 at 100°C under nitrogen atmosphere, then quenched by the addition of water (20mL) at room temperature and extracted with EtOAc (3 x 15 mL). The combined organic layers were washed with brine (1x20 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with DCM /MeOH (15:1) to afford N-tert-butyl-1-{2-[6-(methoxymethoxy)-2-methylindazol-5-yl]- 1,7-naphthyridin-6-yl}pyrrolidin-3-amine (D88, 130 mg). Synthesis of Compound 449 A solution of N-tert-butyl-1-{2-[6-(methoxymethoxy)-2-methylindazol-5-yl]- 1,7-naphthyridin- 6-yl} pyrrolidin-3-amine (110 mg, 0.239 mmol, 1 equiv) in TFA (1 mL) /DCM (1 mL) was treated for 2h at room temperature under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The crude product was purified by Chiral-Prep-HPLC following Condition 15, Gradient 1 as previously described to afford 5-{6-[3-(tert- butylamino)pyrrolidin-1-yl] -1,7-naphthyridin-2-yl}-2-methylindazol-6-ol (Compound 449, 18.4 mg). LCMS: (ES, m/z): 417[M+H] +. ¹ H NMR: (400 MHz, DMSO-d6) δ 13.74 (s, 1H), 9.02 (d, J = 0.9 Hz, 1H), 8.55 (s, 1H), 8.37(s, 1H), 8.33 (d, 1H), 8.21 (dd, J = 9.2, 0.8 Hz, 1H), 6.88 (s, 1H), 6.62 (s, 1H), 4.12 (s, 3H), 3.77 (dd, J = 10.1, 6.8 Hz, 1H), 3.60 (m, 1H), 3.54 (m, 1H), 3.46 – 3.35 (m, 1H), 3.05 (dd, J = 10.1, 7.1 Hz, 1H), 2.25 – 2.14 (m, 1H), 1.77 (dq, J = 11.9, 8.6 Hz, 2H), 1.10 (s, 9H). Example 219: Synthesis of Compound 458 Synthesis of Intermediate D90

Into a 40mL vial were added 2-bromopyrido[3,2-d]pyrimidin-6-ol (D89, 500 mg, 2.212 mmol, 1 equiv), tert-butyl (7E)-7-[(4-methylbenzenesulfonamido)imino]-4-azaspiro[2.5]oc tane-4- carboxylate (870.45 mg, 2.212 mmol, 1 equiv), t-BuOLi (531.29 mg, 6.636 mmol, 3 equiv), dioxane (20 mL), Pd2(dba) ₃ (202.57 mg, 0.221 mmol, 0.1 equiv) and Xphos (105.46 mg, 0.221 mmol, 0.1 equiv) at room temperature. The resulting mixture was stirred overnight at 110°C under nitrogen atmosphere and subsequently allowed to cool to room temperature. The reaction was quenched by the addition of water (30mL) at room temperature and extracted with CH ₂ Cl ₂ /MeOH (3:1) (4 x30 mL). The combined organic layers were washed with brine (1x20 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by trituration with ethyl acetate:PE=5:1 (20mL), and the precipitated solids were collected by filtration and washed with PE (3x3 mL). The crude product (D90) was used in the next step directly without further purification. LCMS: (ES, m/z):355 [M+H] ⁺ . Into a 40mL vial were added tert-butyl 7-{6-hydroxypyrido[3,2-d]pyrimidin-2-yl}-4- azaspiro[2.5]oct -7-ene-4-carboxylate (D90, 270 mg, 0.762 mmol, 1 equiv), K ₂ CO ₃ (315.87 mg, 2.286 mmol, 3 equiv), Et3N (231.28 mg, 2.286 mmol, 3 equiv) and dioxane (13.5 mL) at room temperature, and the resulting mixture was stirred for 4 h at 100 C under nitrogen atmosphere. A solution of 6-(methoxymethoxy)-2-methyl-5-(4,4,5,5-tetramethyl -1,3,2-dioxaborolan-2- yl)indazole (484.80 mg, 1.524 mmol, 2 equiv) in 1,4-dioxane was added, followed by addition of Pd(dppf)Cl ₂ CH ₂ Cl ₂ (62.06 mg, 0.076 mmol, 0.1 equiv) and H ₂ O (0.61 mL)The resulting mixture was stirred for 6h at 100°C under nitrogen atmosphere and later allowed to cool to room temperature. The reaction was quenched by the addition of water (20mL) at room temperature and then extracted with EtOAc (3 x 15 mL). The combined organic layers were washed with brine (1x20 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:4) to afford the mixture (D91, 220 mg) as a solid. LCMS: (ES, m/z):529 [M+H] ⁺ . Into a 25 mL round-bottom flask were added tert-butyl 7-{6-[6-(methoxymethoxy)-2- methylindazol-5-yl]pyrido[3,2-d]pyrimidin-2-yl}-4-azaspiro[2 .5]oct-7-ene-4-carboxylate (D91 isomer, 80 mg, 0.151 mmol, 1 equiv), MeOH (2.4 mL, 74.096 mmol, 489.60 equiv) and PtO ₂ (6.87 mg, 0.030 mmol, 0.2 equiv) at room temperature. The resulting mixture was stirred for 4h at 40°C under hydrogen(1MPa) atmosphere. The resulting mixture was filtered, washed with MeOH (3x3 mL), and concentrated under reduced pressure. Into an 8 mL vial were added the mixture, DCE (3 mL, 37.898 mmol, 250.42 equiv) and MnO ₂ (263.14 mg, 3.020 mmol, 20 equiv) at room temperature. The resulting mixture was stirred for 5 h at 80°C and subsequently filtered, washed with MeOH (3x3 mL), and concentrated under reduced pressure. The crude product (D92) was used in the next step directly without further purification. LCMS: (ES, m/z): 531[M+H] ⁺ . Synthesis of Compound 448 Into a 40mL vial were added tert-butyl 7-{6-[6-(methoxymethoxy)-2-methylindazol-5-yl]pyrido [3,2-d]pyrimidin-2-yl}-4-azaspiro[2.5]octane-4-carboxylate (D92, 27 mg, 0.051 mmol, 1 equiv) and TFA (0.3 mL, 0.001 mmol, 0.02 equiv) and DCM(3 mL) at room temperature. The resulting mixture was stirred for 1h at room temperature, basified to pH 8 with NH ₃ /MeOH, and subsequently concentrated under reduced pressure. The crude product (30 mg) was purified by Prep-HPLC following Condition 17, Gradient 1 as previously described to afford 5-(2-{4- azaspiro[2.5]octan-7-yl} pyrido[3,2-d]pyrimidin-6-yl)-2-methylindazol-6-ol (Compound 448, 9.5 mg). LCMS: (ES, m/z):387 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d6) δ 12.43 (s, 1H), λ.68 (d, J = 0.9 Hz, 1H), 8.75 (d, J = 9.3 Hz, 1H), 8.62 (s, 1H), 8.49 – 8.41 (m, 2H), 6.96 (s, 1H), 4.13 (s, 3H), 3.29 (s, 1H), 3.04 (d, J = 12.7 Hz, 1H), 2.82 – 2.71 (m, 1H), 2.22 (t, J = 12.3 Hz, 1H), 2.02 (d, J = 12.9 Hz, 1H), 1.79 (qd, J = 12.4, 4.1 Hz, 1H), 1.42 (dd, J = 12.4, 3.5 Hz, 1H), 0.56 (q, J = 6.0 Hz, 1H), 0.46 (d, J = 6.0 Hz, 2H), 0.40 (q, J = 6.0 Hz, 1H). Synthesis of Compound 458 Into a 8mL vial were added tert-butyl 7-{6-[6-(methoxymethoxy)-2-methylindazol-5- yl]pyrido[3,2-d] pyrimidin-2-yl}-4-azaspiro[2.5]oct-6-ene-4-carboxylate (D91 isomer, 50 mg, 0.095 mmol, 1 equiv) and TFA (0.3 mL, 26.926 mmol, 284.67 equiv) and DCM(3 mL) at room temperature. The resulting mixture was stirred for 2h at room temperature, basified to pH 8 with NH ₃ /MeOH, and subsequently concentrated under reduced pressure. The crude product (50 mg) was purified by Prep-HPLC following Condition 16, Gradient 2 as previously delineated with the following conditions to afford 5-(2-{4-azaspiro[2.5]oct-6-en-7-yl} pyrido[3,2-d]pyrimidin-6-yl)- 2-methylindazol-6-ol;5-(6-{4-azaspiro[2.5]oct-7-en-7-yl}-1,5 -naphthyridin-2-yl)-2- methylindazol-6-ol (Compound 458, 4.5 mg). LCMS: (ES, m/z):385 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d6) δ 12.27 (s, 1H), λ.57 (d, J = 15.9 Hz, 1H), 8.67 (dd, J = 9.2, 3.3 Hz, 1H), 8.56 (s, 1H), 8.38 (dd, J = 9.1, 2.9 Hz, 1H), 8.35 (s, 1H), 7.60 – 7.03 (m, 1H), 6.95 (s, 1H), 6.95 (s, 1H), 4.12 (s, 3H), 3.54 (s, 1H), 2.71 – 2.65 (m, 1H), 2.62 (q, J = 2.4 Hz, 2H), 2.17 (s, 1H), 0.91 (t, J = 2.3 Hz, 1H), 0.61 – 0.44 (m, 3H). Example 220: Synthesis of Compound 434 To a stirred solution of tert-butyl N-cyclopropyl-N-[(3R)-1-{6-hydroxypyrido[3,2-d]pyrimidin- 2-yl}pyrrolidin-3-yl]carbamate (D93, 150 mg, 0.404 mmol, 1 equiv) and TEA (122 mg, 1.212 mmol, 3 equiv) in dioxane (10 mL) were added K ₂ CO ₃ (167 mg, 1.212 mmol, 3 equiv) and PyBrOP (282 mg, 0.606 mmol, 1.5 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 100°C before the addition of Pd(dppf)Cl ₂ (29 mg, 0.040 mmol, 0.1 equiv), 5-(methoxymethoxy)-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dio xaborolan-2- yl)-1,3-benzoxazole (258 mg, 0.808 mmol, 2 equiv) and H ₂ O (0.5 mL) at room temperature. The resulting mixture was stirred for additional 2 h at 100°C and subsequently purified by reverse flash chromatography following Condition 10, Gradient 1 as previously described to afford tert- butyl N-cyclopropyl-N-[(3R)-1-{7-[5-(methoxymethoxy)-2-methyl-1,3- benzoxazol-6- yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin-3-yl]carbamate (D94, 120 mg). LCMS: (ES, m/z): 547 [M+H] ⁺ . Synthesis of Compound 434 A solution of Intermediate D94 (120 mg, 0.220 mmol, 1 equiv) and trifluoroacetic acid (2 mL) in DCM (10 mL) was stirred for 3 h at room temperature and subsequently concentrated under vacuum. The residue was purified by reverse flash chromatography following Condition 10, Gradient 3 as previously described to afford 6-{2-[(3R)-3-(cyclopropylamino)pyrrolidin-1- yl]pyrido[3,2-d]pyrimidin-6-yl}-2-methyl-1,3-benzoxazol-5-ol (Compound 434, 25 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 403 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 13.5λ (s, 1H), λ.31 (s, 1H), 8.56 (d, J = 9.3 Hz, 1H), 8.39 (s, 1H), 8.06 (d, J = 9.2 Hz, 1H), 7.15 (s, 1H), 3.77 (s, 1H), 3.65 (s, 1H), 3.50 (s, 2H), 3.16 (s, 2H), 2.62 (s, 3H), 2.13 (s, 2H), 1.93 (s, 1H), 0.45-0.39 (m, 2H), 0.26 (s, 2H). Example 221: Synthesis of Compound 432 Synthesis of Intermediate D96 To a stirred solution of 2-bromopyrido[3,2-d]pyrimidin-6-ol (D95, 150 mg, 0.664 mmol, 1 equiv), Cs ₂ CO ₃ (648 mg, 1.992 mmol, 3 equiv) and tert-butyl N-cyclopropyl-N-[(3R)-pyrrolidin- 3-yl]carbamate (180 mg, 0.797 mmol, 1.2 equiv) in dioxane (5 mL) was added Pd-PEPPSI- IPentCl 2-methylpyridine (o-picoline) (27 mg, 0.033 mmol, 0.05 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 100°C and subsequently concentrated under reduced pressure. The residue was purified by reverse flash chromatography following Condition 9, Gradient 1 as previously described to afford tert-butyl N-cyclopropyl-N- [(3R)-1-{6-hydroxypyrido[3,2-d] pyrimidin-2-yl}pyrrolidin-3-yl]carbamate (D96, 150 mg). LCMS: (ES, m/z): 372 [M+H] ⁺ . To a stirred solution of Intermediate D96 (150 mg, 0.404 mmol, 1 equiv) and TEA (122 mg, 1.212 mmol, 3 equiv) in dioxane (10 mL) were added K ₂ CO ₃ (167 mg, 1.212 mmol, 3 equiv) and PyBrOP (282.39 mg, 0.606 mmol, 1.5 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 100°C before adding Pd(dppf)Cl ₂ (29 mg, 0.040 mmol, 0.1 equiv), 5-(methoxymethoxy)-2,4-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2 -dioxaborolan- 2-yl)-1,3-benzoxazole (269 mg, 0.808 mmol, 2 equiv) and H ₂ O (0.5 mL) at room temperature. The resulting mixture was stirred for additional 2 h at 100°C and then purified by reverse flash chromatography following Condition 10, Gradient 1 as previously delineated to afford tert-butyl N-cyclopropyl-N-[(3R)-1-{6-[5-(methoxymethoxy)-2,4-dimethyl- 1,3-benzoxazol-6- yl]pyrido[3,2-d]pyrimidin-2-yl}pyrrolidin-3-yl]carbamate (D97, 120 mg). LCMS: (ES, m/z): 561 [M+H] ⁺ . A solution of Intermediate D97 (120 mg, 0.214 mmol, 1 equiv) and trifluoroacetic acid (2 mL) in DCM (10 mL) was stirred for 3 h at room temperature, subsequently concentrated under vacuum, quenched by the addition of NH ₃ (g) in MeOH (2 mL) at room temperature, and concentrated under reduced pressure. The residue was purified by reverse flash chromatography following Condition 10, Gradient 3 as previously described to afford 6-{2-[(3R)-3- (cyclopropylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyrimidin-6-y l}-2,4-dimethyl-1,3-benzoxazol- 5-ol (Compound 432, 15 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 417 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 14.33 (s, 1H), 9.32 (s, 1H), 8.57 (d, J = 9.3 Hz, 1H), 8.25 (s, 1H), 8.06 (d, J = 9.2 Hz, 1H), 3.77 (s, 2H), 3.62 (s, 2H), 3.50 (s, 2H), 2.62 (s, 3H), 2.56 (s, 3H), 2.40 (s, 2H), 1.9-1.90 (m, 1H), 0.43 (d, J = 6.7 Hz, 2H), 0.27 (s, 2H). Example 222: Synthesis of Compounds 495 and 496 Into a 25 mL round-bottom flask were added tert-butyl 7-{6-[6-(methoxymethoxy)-2- methylindazol-5-yl] -1,5-naphthyridin-2-yl} -4-azaspiro[2.5]octane-4-carboxylate (D98, 95 mg, 0.179 mmol, 1 equiv), DCM (3 mL) and TFA (0.3 mL, 4.039 mmol, 22.52 equiv) at room temperature and allowed to stir for 1 h at room temperature. The mixture was then basified to pH 8 with NH ₃ /MeOH and concentrated under reduced pressure. The crude product (100mg) was purified by Prep-HPLC following Condition 18, Gradient 1 as previously described to afford 5- (6-(4-azaspiro[2.5]octan-7-yl)-1,5-naphthyridin-2-yl)-2-meth yl-2H-indazol-6-ol (27 mg), which was further purified by Chiral-HPLC following Condition 16, Gradient 1 as previously delineated to afford 5-{6-[(7R)-4-azaspiro[2.5]octan-7-yl]-1,5-naphthyridin-2-yl} -2- methylindazol-6-ol (Compound 495, 5.3 mg) and 5-{6-[(7S)-4-azaspiro[2.5]octan-7-yl]-1,5- naphthyridin-2-yl} -2-methylindazol-6-ol (Compound 496, 4.6 mg). Absolute stereochemistry was assigned arbitrarily. Compound 495 was resolved from the first peak. LCMS: (ESI, m/z): 387 [M+H]. ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 13.62 (s, 1H), 8.6λ (s, 1H), 8.60 (d, J = 9.3 Hz, 1H), 8.47 (d, J = 9.1 Hz, 1H), 8.44 – 8.38 (m, 2H), 7.78 (d, J = 8.8 Hz, 1H), 6.92 (s, 1H), 4.13 (s, 3H), 3.29 – 3.18 (m, 1H), 3.07 – 2.99 (m, 1H), 2.75 (td, J = 12.6, 2.8 Hz, 1H), 2.19 (t, J = 12.3 Hz, 1H), 1.92 (d, J = 12.7 Hz, 1H), 1.74 (qd, J = 12.4, 4.1 Hz, 1H), 1.30 (ddd, J = 12.9, 3.9, 1.7 Hz, 1H), 0.60 – 0.52 (m, 1H), 0.51 – 0.37 (m, 3H). Compound 496 was resolved from the second peak. LCMS: (ESI, m/z): 387 [M+H]. ¹ H NMR: (400 MHz, DMSO-d6) δ 13.62 (s, 1H), 8.6λ (s, 1H), 8.60 (d, J = 9.2 Hz, 1H), 8.47 (d, J = 9.1 Hz, 1H), 8.41 (d, J = 8.4 Hz, 2H), 7.77 (d, J = 8.7 Hz, 1H), 6.92 (s, 1H), 4.13 (s, 3H), 3.23 (tt, J = 12.0, 3.7 Hz, 1H), 3.02 (ddd, J = 12.6, 4.2, 2.2 Hz, 1H), 2.75 (td, J = 12.7, 2.8 Hz, 1H), 2.24 – 2.13 (m, 1H), 1.91 (d, J = 12.7 Hz, 1H), 1.73 (qd, J = 12.4, 4.1 Hz, 1H), 1.34 – 1.11 (m, 1H), 0.56 (td, J = 8.3, 7.7, 4.0 Hz, 1H), 0.44 (tdd, J = 11.9, 8.4, 5.6 Hz, 3H). Example 223: Synthesis of Compound 444 Synthesis of Intermediate D100 Into a 40 mL sample bottle were added 6-chloro-1H-1,7-naphthyridin-2-one (150 mg, 0.83 mmol, 1 equiv), (3R)-N-tert-butylpyrrolidin-3-amine (D99, 177.23 mg, 1.24 mmol, 1.5 equiv), Cs ₂ CO ₃ (811.89 mg, 2.49 mmol, 3 equiv), Pd-PEPPSI-IPentCl 2-methylpyridine (o-picoline) (69.87 mg, 0.083 mmol, 0.1 equiv) and dioxane (7.5 mL). The resulting mixture was stirred for 24 h at 100°C under nitrogen atmosphere, later allowed to cool down to room temperature, and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with CH ₂ Cl ₂ / MeOH (10:1) to afford 6-[(3R)-3-(tert- butylamino)pyrrolidin-1-yl]-1H-1,7-naphthyridin-2-one (D100, 300 mg, crude). LCMS: 287[M+H] ⁺ . Synthesis of Intermediate D101 Into an 8 mL sample bottle were Intermediate D100 (100 mg, 0.34 mmol, 1 equiv), PyBrOP (244.18 mg, 0.52 mmol, 1.5 equiv), TEA (106.01 mg, 1.04 mmol, 3 equiv), K ₂ CO ₃ (144.78 mg, 1.04 mmol, 3 equiv) and dioxane (2 mL). The resulting mixture was stirred for 3 h at 100°C under nitrogen atmosphere. Then 5-(methoxymethoxy)-2,4-dimethyl-6-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1,3-benzoxazole (116.35 mg, 0.34 mmol, 1 equiv), Pd(dppf)Cl ₂ CH ₂ Cl ₂ (28.45 mg, 0.035 mmol, 0.1 equiv) and H ₂ O (0.1 mL) were added, and the resulting mixture was stirred for overnight at 100°C under nitrogen atmosphere. The reaction was quenched with water (5 mL) and subsequently extracted with CH ₂ Cl ₂ (3 x 10 mL). The combined organic layers were washed with a half of sat. NaCl (aq.) (2 x 30 mL) and sat. NaCl (aq.) (30 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with CH ₂ Cl ₂ / MeOH (9:1) to afford (3R)-N-tert-butyl-1-{2-[5-(methoxymethoxy)-2,4-dimethyl-1,3- benzoxazol-6-yl]-1,7-naphthyridin-6-yl}pyrrolidin-3-amine (D101,100 mg). LCMS: 476[M+H] ⁺ . Synthesis of Compound 444 Into an 8 mL sample bottle were added Intermediate D101 (10 mg, 0.021 mmol, 1 equiv), DCM (2 mL) and TFA (2 mL), which was stirred for overnight at room temperature and subsequently concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 17, Gradient 2 as previously described to afford 6-{6-[(3R)-3-(tert- butylamino)pyrrolidin-1-yl]-1,7-naphthyridin-2-yl}-2,4-dimet hyl-1,3-benzoxazol-5-ol (Compound 444, 9.9 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: 432[M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 14.λ0 (s, 1H), λ.08 (s, 1H), 8.38 (s, 1H), 8.22 (m, 2H), 6.64 (s, 1H), 3.82 (m, 1H), 3.52 (m, 1H), 3.38 (s, 1H), 3.38 (m, 1H), 3.06 (s, 1H), 2.62 (s, 3H), 2.41 (s, 3H), 2.19 (s, 1H), 1.84 (m, 1H), 1.09 (s, 9H). Example 224: Synthesis of Compound 445 Synthesis of Intermediate D102 Into a 40 mL sample bottle were added Intermediate D99 (150 mg, 0.83 mmol, 1 equiv), (3S)-N- tert-butylpyrrolidin-3-amine (177.23 mg, 1.24 mmol, 1.5 equiv), Cs ₂ CO ₃ (811.89 mg, 2.49 mmol, 3 equiv), Pd-PEPPSI-IPentCl 2-methylpyridine (o-picoline) (69.87 mg, 0.083 mmol, 0.1 equiv) and dioxane (7.5 mL). The resulting mixture was stirred for 24 h at 100°C under nitrogen atmosphere, then allowed to cool to room temperature, and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with CH ₂ Cl ₂ / MeOH (10:1) to afford 6-[(3S)-3-(tert-butylamino)pyrrolidin-1-yl]-1H-1,7- naphthyridin-2-one (D102, 200 mg). LCMS: 287[M+H] ⁺ . Synthesis of Intermediate D103 Into an 8 mL sample bottle were Intermediate D102 (180 mg, 0.62 mmol, 1 equiv), PyBrOP (439.52 mg, 0.94 mmol, 1.5 equiv), TEA (190.81 mg, 1.88 mmol, 3 equiv), K ₂ CO ₃ (260.6 mg, 1.88 mmol, 3 equiv) and dioxane (4 mL). The resulting mixture was stirred for 3 h at 100°C under nitrogen atmosphere. Then 5-(methoxymethoxy)-2,4-dimethyl-6-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1,3-benzoxazole (209.42 mg, 0.62 mmol, 1 equiv), Pd(dppf)Cl ₂ CH ₂ Cl ₂ (45.99 mg, 0.063 mmol, 0.1 equiv) and H ₂ O (0.2 mL) were added, and the resulting mixture was stirred for overnight at 100°C under nitrogen atmosphere. The reaction was quenched with water (5 mL) and then extracted with CH ₂ Cl ₂ (3 x 10 mL). The combined organic layers were washed with a half of sat. NaCl (aq.) (2 x 30 mL) and sat. NaCl (aq.) (30 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with CH ₂ Cl ₂ / MeOH (9:1) to afford (3S)-N-tert- butyl-1-{2-[5-(methoxymethoxy)-2,4-dimethyl-1,3-benzoxazol-6 -yl]-1,7-naphthyridin-6- yl}pyrrolidin-3-amine (D103, 450 mg). Synthesis of Compound 445 Into a 40 mL sample bottle were added Intermediate D103 (200 mg, 0.16 mmol, 1 equiv), DCM (4 mL) and TFA (4 mL), which was stirred overnight at room temperature and later concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 11, Gradient 4 as previously described to afford 6-{6-[(3S)-3-(tert-butylamino)pyrrolidin-1-yl]-1,7- naphthyridin-2-yl}-2,4-dimethyl-1,3-benzoxazol-5-ol (Compound 445, 20.6 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 432[M+H]. ⁺ . ¹ H NMR: (400 MHz, DMSO-d6) δ 14.λ0 (s, 1H), λ.08 (s, 1H), 8.38 (d, J = 9.4 Hz, 1H),8.22 (m, 2H), 6.65 (s, 1H), 3.78 (dd, J = 10.0, 6.8 Hz, 1H), 3.59 (dt, J = 21.7, 8.4 Hz, 2H), 3.47 (m, 1H), 3.07 (dd, J = 10.2, 7.2 Hz, 1H), 2.62 (s, 3H), 2.41 (s, 3H), 2.16 (m, 1H), 1.86 (m, 1H), 1.10 (s, 9H). Example 225: Synthesis of Compounds 497-500 Synthesis of Intermediate D105 Into a 250 mL 3-necked round-bottom flask were added Intermediate D104 (5 g, 18.376 mmol, 1 equiv), KOAc (5.41 g, 55.128 mmol, 3 equiv), dioxane (100 mL), and Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (1.50 g, 1.838 mmol, 0.1 equiv) at room temperature. The resulting mixture was stirred for 3 h at 100°C under nitrogen atmosphere and subsequently allowed to cool to room temperature. The resulting mixture was filtered, washed with EtOAc (3 x 10 mL), and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE/EA (3:1) to afford 5-(methoxymethoxy)-2-methyl-6-(4,4,5,5-tetramethyl -1,3,2- dioxaborolan-2-yl)-1,3-benzoxazole (D105, 4.8 g). LCMS: (ESI, m/z): 320 [M+H] Into a 20 mL vial were added Intermediate D105 (400 mg, 1.253 mmol, 1 equiv),2,6-dichloro- 1,5-naphthyridine (249.44 mg, 1.253 mmol, 1 equiv), dioxane (8 mL), K ₃ PO ₄ (798.09 mg, 3.759 mmol, 3 equiv) in H ₂ O (1.6 mL) and Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (91.7 mg, 0.125 mmol, 0.1 equiv) at room temperature. The resulting mixture was stirred for 3 h at 100°C under nitrogen atmosphere, then allowed to cool to room temperature, and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with CH ₂ Cl ₂ /EA (3:2) to afford 2-chloro-6-[5-(methoxymethoxy)-2-methyl-1,3-benzoxazol-6-yl] -1,5- naphthyridine (D106, 250 mg). LCMS: (ESI, m/z): 356 [M+H]. Synthesis of Intermediate D107 Into a 40 mL vial were added Intermediate D106 (400 mg, 1.124 mmol, 1 equiv), dioxane (12 mL, 141.648 mmol, 125.99 equiv), K3PO4 (715.94 mg, 3.372 mmol, 3 equiv) and Pd(PPh3)4 (129.92 mg, 0.112 mmol, 0.1 equiv) at room temperature. The resulting mixture was stirred for overnight at 100°C under nitrogen atmosphere. The mixture was allowed to cool to room temperature, quenched by the addition of water (10 mL) at room temperature, and lastly concentrated under reduced pressure. The residue was then purified by silica gel column chromatography and eluted with PE / EA (1:3) to afford mixture product (D107, 220 mg) as a yellow solid. LCMS: (ESI, m/z): 529 [M+H]. Into a 25 mL round-bottom flask were added the mixture tert-butyl 7-{6-[5-(methoxymethoxy)- 2-methyl-1,3-benzoxazol-6-yl]-1,5-naphthyridin-2-yl}-4-azasp iro[2.5]oct-6-ene-4-carboxylate and tert-butyl 7-{6-[5-(methoxymethoxy)-2-methyl-1,3-benzoxazol-6-yl]-1,5-n aphthyridin-2-yl} -4-azaspiro[2.5]oct-7-ene-4-carboxylate (D107, 180 mg, 0.170 mmol, 1 equiv), MeOH (1 mL, 24.699 mmol, 145.07 equiv) and Pd/C (5.44 mg, 0.051 mmol, 0.3 equiv) at room temperature. The resulting mixture was stirred overnight at 35°C under hydrogen atmosphere. Trace desired product was detected by LCMS. The resulting mixture was filtered and the filter cake was washed with DCM and MeOH (2:1,3x3 mL), then concentrated under reduced pressure. The crude mixture in DCE (5 mL) was treated with MnO ₂ (148.02 mg, 1.700 mmol, 10 equiv) overnight at 80 °C and subsequently allowed to cool to room temperature. The resulting mixture was filtered, washed with DCM and MeOH (2:1,3x3 mL), and the filtrate was concentrated under reduced pressure. The residue was purified by Prep-TLC (CH ₂ Cl ₂ / MeOH 10:1) to afford tert-butyl 7-{6-[5-(methoxymethoxy)-2-methyl-1,3-benzoxazol-6-yl] -1,5-naphthyridin-2-yl}-4- azaspiro[2.5]octane-4-carboxylate (D108, 80 mg). LCMS: (ESI, m/z): 531 [M+H]. Synthesis of Compounds 497 and 498

Into a 20 mL vial were added Intermediate D108 (85 mg, 0.160 mmol, 1 equiv), DCM (5 mL) and TFA (0.5 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature, basified to pH 8 with NH ₃ /MeOH, and then concentrated under reduced pressure. The crude product (80 mg) was purified by Prep-HPLC following Condition 11, Gradient 5 as previously described to afford 6-(6-(4-azaspiro[2.5]octan-7-yl)-1,5-naphthyridin-2-yl) -2- methylbenzo[d]oxazol-5-ol (25 mg), which was purified by Chiral-HPLC following Condition 17, Gradient 1 as previously described to afford 6-{6-[(7S)-4-azaspiro[2.5]octan-7-yl] -1,5- naphthyridin-2-yl}-2-methyl-1,3-benzoxazol-5-ol (Compound 497, 9.9 mg) and 6-{6-[(7R)-4- azaspiro[2.5]octan-7-yl]-1,5-naphthyridin-2-yl} -2-methyl-1,3-benzoxazol-5-ol (Compound 498, 9.4 mg). Compounds 497 and 498 were resolved from the first and second peaks, respectively. Absolute stereochemistry of the compounds was arbitrarily assigned. Analytical data for the respective compounds are shown in the Table below. Synthesis of Compounds 499 and 500 As would be manifest to a person of skill in the art, Compounds 499 and 500 (shown in the Table below) were synthesized following a similar synthetic scheme as described above in this Example. Compounds 499 and 500 were resolved from the first and second peaks, respectively, by Chiral HPLC. Absolute stereochemistry of the compounds was assigned arbitrarily.

Example 226: Synthesis of Compound 504 Synthesis of Intermediate D110 To a stirred solution of 6-bromo-7-methoxy-2,8-dimethylimidazo[1,2-a]pyridine (D109, 2.5 g, 9.8 mmol, 1 equiv), KOAc (1.93 g, 19.6 mmol, 2 equiv) and bis(pinacolato)diboron (3.73 g, 14.7 mmol, 1.5 equiv) in dioxane (40 mL) were added PCy ₃ (1.65 g, 5.88 mmol, 0.6 equiv) and Pd2(dba) ₃ (2.69 g, 2.94 mmol, 0.3 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 h at 100°C under nitrogen atmosphere and subsequently allowed to cool to room temperature. To the above mixture were added 2-bromopyrido[3,2- d]pyrimidin-6-ol (2.22 g, 9.8 mmol, 1 equiv), K ₂ CO ₃ (2.72 g, 19.6 mmol, 2 equiv), XPhos (2.81 g, 5.88 mmol, 0.6 equiv) and Pd2(dba) ₃ (2.69 g, 2.94 mmol, 0.3 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for additional 3 h at 100°C, then allowed to cool to room temperature, and finally concentrated under vacuum. The residue was purified by reversed-phase flash chromatography following Condition 7, Gradient 7 as previously described to afford 2-{7-methoxy-2,8-dimethylimidazo[1,2-a]pyridin-6- yl}pyrido[3,2-d]pyrimidin-6-ol (D110, 400 mg). LCMS: (ES, m/z): 322 [M+H] ⁺ . Synthesis of D111 To a stirred solution of Intermediate D110 (300 mg, 0.934 mmol, 1 equiv) and tert-butyl N- methyl-N-[(3R)-pyrrolidin-3-yl]carbamate (281 mg, 1.401 mmol, 1.5 equiv) in ACN (5 mL) were added BOP (826 mg, 1.868 mmol, 2 equiv) and DBU (427 mg, 2.802 mmol, 3 equiv) at room temperature. The resulting mixture was stirred for overnight at room temperature and later concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography following Condition 10, Gradient 11 as previously described to afford tert-butyl N-[(3R)-1-(2-{7-methoxy-2,8-dimethylimidazo[1,2-a]pyridin-6- yl}pyrido[3,2-d]pyrimidin-6- yl)pyrrolidin-3-yl]-N-methylcarbamate (D111, 280 mg). LCMS: (ES, m/z): 504 [M+H] ⁺ . Synthesis of Compound 504 To a stirred solution of Intermediate D111 (300 mg, 0.596 mmol, 1 equiv) in DCE (5 mL) was added BBr3 (157 mg, 0.626 mmol, 1.05 equiv) at room temperature. The resulting mixture was stirred for 1 h at 70°C, subsequently allowed to cool to room temperature, and lastly concentrated under vacuum. The residue was purified by reversed-phase flash chromatography following Condition 10, Gradient 27 as previously described to afford 2,8-dimethyl-6-{6-[(3R)- 3-(methylamino)pyrrolidin-1-yl]pyrido[3,2-d]pyrimidin-2-yl}i midazo[1,2-a]pyridin-7-ol (Compound 504, 60 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 390 [M+H] ⁺ . ¹ H NMR: (300 MHz, DMSO-d6) δ 13.1λ (s, 1H), λ.35 (s, 1H), 9.20 (s, 1H), 8.13 (d, J = 9.4 Hz, 1H), 7.64 (s, 1H), 7.37 (d, J = 9.4 Hz, 1H), 3.66 (d, J = 5.6 Hz, 3H), 3.32 (s, 1H), 2.41-2.21 (m, 9H), 2.23-1.77 (m, 3H). Example 227: Synthesis of Compound 505 Synthesis of Intermediate D113 To a stirred mixture of ethyl 2,6-dichloroquinazoline-4-carboxylate (D112, 200 mg, 0.738 mmol, 1 equiv) and 8-fluoro-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl) imidazo[1,2- a]pyridine (244.44 mg, 0.886 mmol, 1.2 equiv) in dioxane (3 mL) and H ₂ O (0.6 mL) were added K3PO4 (234.89 mg, 1.107 mmol, 1.5 equiv) and Pd(dppf)Cl ₂ (53.98 mg, 0.074 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 80°C under nitrogen atmosphere and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford ethyl 6- chloro-2-{8-fluoro-2-methylimidazo[1,2-a] pyridin-6-yl}quinazoline-4-carboxylate (D113, 160 mg). LCMS: (ES, m/z): 385 [M+H] ⁺ . Synthesis of Intermediate D114

To a stirred mixture of Intermediate D113 (160 mg, 0.416 mmol, 1 equiv) and tert-butyl piperazine-1-carboxylate (100.68 mg, 0.541 mmol, 1.3 equiv) in dioxane (3 mL) were added Cs2CO ₃ (406.43 mg, 1.248 mmol, 3 equiv), X-Phos (39.64 mg, 0.083 mmol, 0.2 equiv) and Pd ₂ (dba) ₃ (38.08 mg, 0.042 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 80°C under nitrogen atmosphere and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with DCM / MeOH (20:1) to afford ethyl 6-[4-(tert-butoxycarbonyl) piperazin-1-yl]-2-{8-fluoro-2-methylimidazo[1,2-a] pyridin-6-yl} quinazoline-4-carboxylate (D114, 180 mg). LCMS: (ES, m/z): 535 [M+H] ⁺ . Synthesis of Intermediate D115 Intermediate D114 (180 mg, 0.337 mmol, 1 equiv) was added to a stirred solution of 2.0 M methylamine in THF (8 mL) at room temperature. The resulting mixture was stirred overnight at 80°C and then concentrated under reduced pressure to afford tert-butyl 4-(2-{8-fluoro-2- methylimidazo[1,2-a] pyridin-6-yl}-4-(methylcarbamoyl) quinazolin-6-yl) piperazine-1- carboxylate (D115, 49 mg). LCMS: (ES, m/z): 520 [M+H] ⁺ . Synthesis of Compound 505

To a stirred solution of Intermediate D115 (49 mg, 0.094 mmol, 1 equiv) in dioxane (0.5 mL) was added HCl (gas) in 1,4-dioxane (0.5 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature, concentrated under reduced pressure, and the crude product was purified by Prep-HPLC following Condition 13, Gradient 3 as previously described to afford 2-{8-fluoro-2-methylimidazo[1,2-a] pyridin-6-yl}-N-methyl-6-(piperazin-1-yl) quinazoline-4- carboxamide (Compound 505, 10.8 mg). LCMS: (ES, m/z): 420 [M+H] ⁺ . ¹ H NMR: (400 MHz, Methanol-d4) δ λ.43 (d, J = 1.3 Hz, 1H), 8.41 (d, J = 2.7 Hz, 1H), 8.10-7.98 (m, 2H), 7.92 (dd, J = 9.4, 2.8 Hz, 1H), 7.82 (d, J = 2.8 Hz, 1H), 3.71-3.61 (m, 4H), 3.49 (dd, J = 6.8, 3.8 Hz, 4H), 3.11 (s, 3H), 2.49 (s, 3H). Example 228: Synthesis of Compound 507 Synthesis of Intermediate D116 To a stirred mixture of Intermediate D112 (210 mg, 0.775 mmol, 1 equiv) and 6- (methoxymethoxy)-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-d ioxaborolan-2-yl)indazole (283.07 mg, 0.853 mmol, 1.1 equiv) in dioxane/H ₂ O (5:1; 3.6 mL) were added K3PO4 (246.64 mg, 1.163 mmol, 1.5 equiv) and Pd(dppf)Cl ₂ (56.68 mg, 0.078 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 80°C under nitrogen atmosphere and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford ethyl 6-chloro-2-[6- (methoxymethoxy)-2,7-dimethylindazol-5-yl]quinazoline-4-carb oxylate (D116, 230 mg). LCMS: (ES, m/z): 441 [M+H] ⁺ . To a stirred mixture of Intermediate D116 (230 mg, 0.522 mmol, 1 equiv) and N,N- dimethylpiperidin-4-amine (86.96 mg, 0.679 mmol, 1.3 equiv) in dioxane (4.5mL) were added Cs ₂ CO ₃ (509.92 mg, 1.566 mmol, 3 equiv), X-Phos (49.74 mg, 0.104 mmol, 0.2 equiv) and Pd ₂ (dba) ₃ (47.77 mg, 0.052 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 80°C under nitrogen atmosphere and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with DCM / MeOH (20:1) to afford ethyl 6-[4- (dimethylamino)piperidin-1-yl]-2-[6-(methoxymethoxy)-2,7-dim ethylindazol-5-yl]quinazoline- 4-carboxylate (D117, 200 mg). LCMS: (ES, m/z): 533 [M+H] ⁺ . To a stirred solution of Intermediate D117 (200 mg, 0.375 mmol, 1 equiv) in MeOH (2 mL) was added LiOH ^. H ₂ O (31.51 mg, 0.750 mmol, 2 equiv) at room temperature. The resulting mixture was stirred overnight at 40°C, concentrated under vacuum, diluted with H ₂ O (5 mL), and then acidified to pH 6 with HCl (1N). The aqueous layer was extracted with DCM (3 x 100 mL), and the combined organic layers were concentrated under reduced pressure to afford 6-[4- (dimethylamino)piperidin-1-yl]-2-[6-(methoxymethoxy)-2,7-dim ethylindazol-5-yl]quinazoline- 4-carboxylic acid (D118, 150 mg). LCMS: (ES, m/z): 505 [M+H] ⁺ . To a stirred mixture of Intermediate D118 (150 mg, 0.286 mmol, 1 equiv) and methylamine (2M in THF) (9.77 mg, 0.315 mmol, 1.1 equiv) in DCM (3 mL) was added T ₃ P (118.24 mg, 0.372 mmol, 1.3 equiv) and TEA (86.78 mg, 0.858 mmol, 3 equiv) at room temperature. The resulting mixture was stirred overnight at room temperature and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with DCM / MeOH (10:1) to afford {6-[4-(dimethylamino)piperidin-1-yl]-2-[6-(methoxymethoxy)-2 ,7-dimethyl- octahydroindazol-5-yl]-decahydroquinazolin-4-yl}(methylamino )methanol (D119, 15 mg). LCMS: (ES, m/z): 518 [M+H] ⁺ . To a stirred solution of Intermediate D119 (15 mg, 0.029 mmol, 1 equiv) in dioxane (0.5mL) was added HCl (gas) in 1,4-dioxane (0.5 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature and subsequently concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 13, Gradient 2 as previously described to afford 6-[4-(dimethylamino)piperidin-1-yl]-2-(6-hydroxy-2,7-dimethy lindazol-5-yl)-N- methylquinazoline-4-carboxamide (Compound 507, 6 mg). LCMS: (ES, m/z): 420 [M+H] ⁺ . ¹ H NMR: (400 MHz, Chloroform-d) δ 13.55 (s, 1H), 8.84 (s, 1H), 8.81 (d, J = 2.8 Hz, 1H), 8.25 (d, J = 5.6 Hz, 1H), 7.99 (s, 1H), 7.90 (d, J = 9.3 Hz, 1H), 7.73 (dd, J = 9.4, 2.8 Hz, 1H), 4.26 (s, 3H), 4.07 (d, J = 12.7 Hz, 2H), 3.20 (d, J = 5.1 Hz, 3H), 2.99 (t, J = 11.8 Hz, 2H), 2.63 (d, J = 4.3 Hz, 4H), 2.56 (s, 6H), 2.18 (s, 2H), 1.84 (d, J = 12.5 Hz, 2H), 1.28 (s, 2H), 1.07 (s, 1H), 0.86 (s, 3H). Example 229: Synthesis of Compound 508 Synthesis of Intermediate D121 2,4,6-trichloroquinazoline (D120, 210 mg, 0.899 mmol, 1 equiv) was added to a stirred solution of 2M methylamine in THF (8 mL) at room temperature. The resulting mixture was stirred for 2 h at room temperature and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (5:1) to afford 2,6-dichloro-N- methylquinazolin-4-amine (D121, 200 mg). LCMS: (ES, m/z): 228 [M+H] ⁺ . Synthesis of Intermediate D122 To a stirred mixture of Intermediate D121 (150 mg, 0.658 mmol, 1 equiv) and 6- (methoxymethoxy)-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-d ioxaborolan-2-yl) indazole (327.72 mg, 0.987 mmol, 1.5 equiv) in dioxane/H ₂ O (10:1; 3.3 mL) were added K ₂ CO ₃ (272.68 mg, 1.974 mmol, 3 equiv) and Pd(dppf)Cl ₂ (481.22 mg, 0.658 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 80°C under nitrogen atmosphere and later concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford 6-chloro-2-[6- (methoxymethoxy)-2,7-dimethylindazol-5-yl]-N-methylquinazoli n-4-amine (D122, 130 mg). LCMS: (ES, m/z): 398 [M+H] ⁺ . Synthesis of Intermediate D123 To a stirred mixture of Intermediate D122 (130 mg, 0.327 mmol, 1 equiv) and tert-butyl piperazine-1-carboxylate (79.12 mg, 0.425 mmol, 1.3 equiv) in dioxane (2.6 mL) were added Cs2CO ₃ (319.38 mg, 0.981 mmol, 3 equiv), X-Phos (31.15 mg, 0.065 mmol, 0.2 equiv) and Pd2(dba) ₃ (29.92 mg, 0.033 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 80 °C under nitrogen atmosphere and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with DCM/ MeOH (20:1) to afford tert-butyl 4-{2-[6- (methoxymethoxy)-2,7-dimethylindazol-5-yl]-4-(methylamino)qu inazolin-6-yl}piperazine-1- carboxylate (D123, 102 mg). LCMS: (ES, m/z): 578 [M+H] ⁺ . To a stirred solution of Intermediate D123 (102 mg, 0.186 mmol, 1 equiv) in dioxane (1 mL) was added HCl (gas) in 1,4-dioxane (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature and subsequently concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 13, Gradient 5 as previously described to afford 2,7-dimethyl-5-[4-(methylamino)-6-(piperazin-1-yl) quinazolin-2-yl]indazol-6-ol (Compound 508, 17.9 mg). LCMS: (ES, m/z): 404 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d6) δ 14.74 (s, 1H), 8.83 (s, 1H), 8.41 (d, J = 4.6 Hz, 1H), 8.35 (s, 1H), 7.63 (d, J = 9.1 Hz, 1H), 7.59 (dd, J = 9.2, 2.4 Hz, 1H), 7.48 (d, J = 2.4 Hz, 1H), 4.13 (s, 3H), 3.25 – 3.16 (m, 7H), 2.89 (t, J = 5.0 Hz, 4H), 2.36 (s, 3H). Example 230: Synthesis of Compound 509 Synthesis of Intermediate D124 Intermediate D120 (210 mg, 0.899 mmol, 1 equiv) was added to a stirred solution of 2 M dimethylamine in THF (8 mL) at room temperature. The resulting mixture was stirred for 2 h at room temperature and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (5:1) to afford 2,6-dichloro-N, N- dimethylquinazolin-4-amine (D124, 200 mg). LCMS: (ES, m/z): 242 [M+H] ⁺ . Synthesis of Intermediate D125 To a stirred mixture of Intermediate D124 (200 mg, 0.826 mmol, 1 equiv) and 6- (methoxymethoxy)-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-d ioxaborolan-2-yl)indazole (301.88 mg, 0.909 mmol, 1.1 equiv) in dioxane/H ₂ O (10:1, 2.2 mL) were added K ₂ CO ₃ (342.52 mg, 2.478 mmol, 3 equiv) and Pd(dppf)Cl ₂ (60.45 mg, 0.083 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 80 C (under nitrogen atmosphere) and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford 6-chloro-2- [6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]-N, N-dimethylquinazolin-4-amine (D125, 130 mg). LCMS: (ES, m/z): 412 [M+H] ⁺ . Synthesis of Intermediate D126 To a stirred mixture of Intermediate D125 (130 mg, 0.316 mmol, 1 equiv) and tert-butyl piperazine-1-carboxylate (88.18 mg, 0.474 mmol, 1.5 equiv) in dioxane (2.6 mL) were added Cs2CO ₃ (309.46 mg, 0.948 mmol, 3 equiv), X-Phos (30.09 mg, 0.063 mmol, 0.2 equiv) and Pd ₂ (dba) ₃ (28.90 mg, 0.032 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 80°C under nitrogen atmosphere and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with DCM / MeOH (20:1) to afford tert-butyl 4-[4-(dimethylamino)- 2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]quinazolin-6- yl]piperazine-1-carboxylate (D126, 110 mg). LCMS: (ES, m/z): 562 [M+H] ⁺ . Synthesis of Compound 509 To a stirred solution of Intermediate D126 (110 mg, 0.196 mmol, 1 equiv) in dioxane (1mL) was added HCl (gas) in 1,4-dioxane (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature and then concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 13, Gradient 2 as previously delineated to afford 5-[4-(dimethylamino)-6-(piperazin-1-yl)quinazolin-2-yl]-2,7- dimethylindazol-6-ol (Compound 509, 14 mg). LCMS: (ES, m/z): 418 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d6) δ 14.45 (s, 1H), 8.78 (s, 1H), 8.35 (s, 1H), 7.71 (d, J = 9.2 Hz, 1H), 7.65 (dd, J = 9.2, 2.5 Hz, 1H), 7.32 (d, J = 2.5 Hz, 1H), 4.13 (s, 3H), 3.43 (s, 6H), 3.19 (t, J = 5.0 Hz, 4H), 2.89 (t, J = 5.0 Hz, 4H), 2.37 (s, 3H). Example 231: Synthesis of Compound 510 Synthesis of Intermediate D127 To a stirred mixture of Intermediate D116 (160 mg, 0.363 mmol, 1 equiv) and tert-butyl N- methyl-N-(pyrrolidin-3-yl)carbamate (94.49 mg, 0.472 mmol, 1.3 equiv) in dioxane (3 mL) were added Cs ₂ CO ₃ (354.73 mg, 1.089 mmol, 3 equiv), Ruphos (33.87 mg, 0.073 mmol, 0.2 equiv) and RuPhos Palladacycle Gen.3 (30.35 mg, 0.036 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 5 h at 60°C under nitrogen atmosphere and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with DCM / MeOH (20:1) to afford ethyl 6-{3- [(tert-butoxycarbonyl)(methyl)amino]pyrrolidin-1-yl}-2-[6-(m ethoxymethoxy)-2,7- dimethylindazol-5-yl]quinazoline-4-carboxylate (D127, 150 mg). LCMS: (ES, m/z): 605 [M+H] ⁺ . Intermediate D127 (150 mg, 0.248 mmol, 1 equiv) was added to a stirred solution of 2 M methylamine in THF (8 mL) at room temperature. The resulting mixture was stirred overnight at 80°C and then concentrated under reduced pressure to afford tert-butyl N-(1-{2-[6- (methoxymethoxy)-2,7-dimethylindazol-5-yl]-4-(methylcarbamoy l)quinazolin-6-yl}pyrrolidin-3- yl)-N-methylcarbamate (D128, 112 mg). LCMS: (ES, m/z): 590 [M+H] ⁺ . Synthesis of Compound 510 To a stirred solution of Intermediate D128 (75 mg, 0.127 mmol, 1 equiv) in dioxane (1mL) was added HCl (gas) in 1,4-dioxane (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature and subsequently concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 13, Gradient 3 as previously described to afford 2-(6-hydroxy-2,7-dimethylindazol-5-yl)-N-methyl-6-[3-(methyl amino)pyrrolidin-1- yl]quinazoline-4-carboxamide (Compound 510, 13.7 mg). LCMS: (ES, m/z): 446 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 13.47 (s, 1H), λ.14 (d, J = 5.4 Hz, 1H), 9.04 (s, 1H), 8.39 (s, 1H), 7.97 (d, J = 9.2 Hz, 1H), 7.72 (d, J = 2.8 Hz, 1H), 7.58 (dd, J = 9.1, 2.7 Hz, 1H), 4.16 (s, 3H), 3.57 (dd, J = 9.9, 6.0 Hz, 1H), 3.49 (t, J = 7.3 Hz, 1H), 3.42 (d, J = 7.4 Hz, 1H), 3.18 (dd, J = 10.0, 4.4 Hz, 1H), 2.96 (d, J = 4.5 Hz, 3H), 2.40 (s, 3H), 2.34 (s, 3H), 2.21 – 2.11 (m, 1H), 1.97 (s, 1H), 1.89 (dd, J = 12.4, 6.4 Hz, 1H). Example 232: Synthesis of Compound 511 To a stirred mixture of Intermediate D116 (160 mg, 0.363 mmol, 1 equiv) and tert-butyl (2R,6S)- 2,6-dimethylpiperazine-1-carboxylate (116.66 mg, 0.544 mmol, 1.5 equiv) in dioxane (3 mL) were added Cs2CO ₃ (354.73 mg, 1.089 mmol, 3 equiv), RuPhos (33.87 mg, 0.073 mmol, 0.2 equiv) and RuPhos Palladacycle Gen.3 (30.35 mg, 0.036 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 5 h at 60°C under nitrogen atmosphere and later concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with DCM / MeOH (20:1) to afford ethyl 6-[(3R,5S)-4-(tert- butoxycarbonyl)-3,5-dimethylpiperazin-1-yl]-2-[6-(methoxymet hoxy)-2,7-dimethylindazol-5- yl]quinazoline-4-carboxylate (D129, 150 mg). LCMS: (ES, m/z): 619 [M+H] ⁺ . Intermediate D129 (150 mg, 0.242 mmol, 1 equiv) was added to 2 M methylamine in THF (8 mL) at room temperature. The resulting mixture was stirred overnight at 80°C and then concentrated under reduced pressure to afford tert-butyl (2R,6S)-4-{2-[6-(methoxymethoxy)-2,7- dimethylindazol-5-yl]-4-(methylcarbamoyl)quinazolin-6-yl}-2, 6-dimethylpiperazine-1- carboxylate (D130, 124 mg). LCMS: (ES, m/z): 604 [M+H] ⁺ . To a stirred solution of Intermediate D130 (75 mg, 0.124 mmol, 1 equiv) in dioxane (1 mL) was added HCl (gas) in 1,4-dioxane (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature and subsequently concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 13, Gradient 3 as previously delineated to afford 6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-2-(6-hydroxy-2,7-dime thylindazol-5-yl)-N- methylquinazoline-4-carboxamide (Compound 511, 16.9 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 460 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 13.40 (s, 1H), λ.20 (d, J = 5.0 Hz, 1H), 9.09 (s, 1H), 8.42 (s, 1H), 8.14 (d, J = 2.2 Hz, 1H), 8.00 (d, J = 2.9 Hz, 2H), 4.16 (s, 3H), 3.76 (d, J = 10.7 Hz, 2H), 2.97 (d, J = 4.8 Hz, 3H), 2.90 (s, 2H), 2.41 (s, 3H), 2.32 (t, J = 11.1 Hz, 2H), 1.09 (d, J = 6.2 Hz, 6H). Example 233: Synthesis of Compound 512 Synthesis of Intermediate D131 To a stirred mixture of Intermediate D116 (150 mg, 0.340 mmol, 1 equiv) and tert-butyl (2S)-2- methylpiperazine-1-carboxylate (88.58 mg, 0.442 mmol, 1.3 equiv) in dioxane (3mL) were added Cs ₂ CO ₃ (332.56 mg, 1.020 mmol, 3 equiv), RuPhos (31.75 mg, 0.068 mmol, 0.2 equiv) and RuPhos Palladacycle Gen.3 (28.46 mg, 0.034 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 5 h at 60°C under nitrogen atmosphere and later concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with DCM / MeOH (20:1) to afford ethyl 6-[(3S)-4-(tert- butoxycarbonyl)-3-methylpiperazin-1-yl]-2-[6-(methoxymethoxy )-2,7-dimethylindazol-5- yl]quinazoline-4-carboxylate (D131, 150 mg). LCMS: (ES, m/z): 605 [M+H] ⁺ . Intermediate D131 (150 mg, 0.248 mmol, 1 equiv) was added to a stirred solution of 2M methylamine in THF (8 mL) at room temperature. The resulting mixture was stirred overnight at 80°C and then concentrated under reduced pressure to afford tert-butyl (2S)-4-{2-[6- (methoxymethoxy)-2,7-dimethylindazol-5-yl]-4-(methylcarbamoy l) quinazolin-6-yl}-2- methylpiperazine-1-carboxylate (D132, 121 mg). LCMS: (ES, m/z): 560 [M+H] ⁺ . T o a stirred solution of Intermediate D132 (75 mg, 0.127 mmol, 1 equiv) in dioxane (1 mL) was added HCl (gas) in 1,4-dioxane (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature and then concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 13, Gradient 4 as previously described to afford 2-(6-hydroxy-2,7-dimethylindazol-5-yl)-N-methyl-6-[(3S)-3-me thylpiperazin-1-yl] quinazoline- 4-carboxamide (Compound 512, 19.5 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 446 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 13.40 (s, 1H), 9.19 (d, J = 4.7 Hz, 1H), 9.09 (s, 1H), 8.42 (s, 1H), 8.13 (d, J = 1.7 Hz, 1H), 7.99 (d, J = 1.6 Hz, 2H), 4.16 (s, 3H), 3.74 (t, J = 10.3 Hz, 2H), 3.04 (d, J = 11.3 Hz, 1H), 2.97 (d, J = 4.8 Hz, 3H), 2.83 (s, 2H), 2.82 – 2.70 (m, 1H), 2.41 (s, 4H), 1.08 (d, J = 6.3 Hz, 3H). Example 234: Synthesis of Compound 514 Synthesis of Intermediate D134 Ethyl 6-[4-(tert-butoxycarbonyl) piperazin-1-yl]-2-[7-fluoro-6-(methoxymethoxy)-2- methylindazol-5-yl] quinazoline-4-carboxylate (D133, 240 mg, 0.404 mmol, 1 equiv) was added to stirred solution of NH ₃ (g) in MeOH (8 mL) at room temperature. The resulting mixture was stirred overnight at 80°C and subsequently concentrated under reduced pressure to afford tert- butyl 4-{4-carbamoyl-2-[7-fluoro-6-(methoxymethoxy)-2-methylindazo l-5-yl] quinazolin-6-yl} piperazine-1-carboxylate (D134, 200 mg). LCMS: (ES, m/z): 566 [M+H] ⁺ . Synthesis of Intermediate D135 To a stirred solution of Intermediate D134 (200 mg, 0.354 mmol, 1 equiv) in DCM (2 mL) and pyridine (0.2 mL) was added trifluoroacetic anhydride (148.54 mg, 0.708 mmol, 2 equiv) dropwise at 0°C. The resulting mixture was stirred for 1 h at room temperature and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (5:1) to afford tert-butyl 4-{4-cyano-2-[7-fluoro-6- (methoxymethoxy)-2-methylindazol-5-yl] quinazolin-6-yl} piperazine-1-carboxylate (D135, 127 mg). LCMS: (ES, m/z): 548 [M+H] ⁺ . Synthesis of Compound 514 To a stirred solution of Intermediate D135 (127 mg, 0.232 mmol, 1 equiv) in DCM (1 mL) was added TFA (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature and then concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 7, Gradient 4 as previously described to afford 2-(7-fluoro-6- hydroxy-2-methylindazol-5-yl)-6-(piperazin-1-yl) quinazoline-4-carbonitrile; trifluoroacetic acid (Compound 514, 61.2 mg). LCMS: (ES, m/z): 404 [M+H] ⁺ . ¹ H NMR: (400 MHz, Methanol-d4) δ 8.31-8.23 (m, 2H), 7.92 (dd, J = 9.5, 2.6 Hz, 1H), 7.76 (d, J = 9.3 Hz, 1H), 6.73 (d, J = 2.7 Hz, 1H), 4.21 (s, 3H), 3.75-3.68 (m, 4H), 3.52 (t, J = 5.2 Hz, 4H). Example 235: Synthesis of Compound 518 Synthesis of Intermediate D136 Into a 40 mL vial were added Intermediate D120 (1.0 g, 4.283 mmol, 1.0 equiv), cyclopropylboronic acid (0.37 g, 4.283 mmol, 1.0 equiv), THF (20 mL), Pd(dppf)Cl ₂ (0.35 g, 0.428 mmol, 0.1 equiv) and K ₃ PO ₄ (2.73 g, 12.849 mmol, 3.0 equiv) at room temperature. The resulting mixture was stirred overnight at 80°C under nitrogen atmosphere and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (5:1) to afford 2,6-dichloro-4-cyclopropylquinazoline (D136, 0.4 g). LCMS: (ES, m/z): 239 [M+H] ⁺ . Synthesis of Intermediate D137 Into an 8 mL vial were added Intermediate D136 (200 mg, 0.836 mmol, 1.0 equiv), 7-fluoro-6- (methoxymethoxy)-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxa borolan-2-yl)indazole (281.20 mg, 0.836 mmol, 1.0 equiv), dioxane (2 ml), water (0.4 mL), Pd(dppf)Cl ₂ (68.14 mg, 0.084 mmol, 0.1 equiv) and K ₃ PO ₄ (532.66 mg, 2.508 mmol, 3.0 equiv) at room temperature. The resulting mixture was stirred overnight at 80°C under nitrogen atmosphere and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (3:1) to afford 6-chloro-4-cyclopropyl-2-[7-fluoro-6-(methoxymethoxy)-2- methylindazol-5-yl]quinazoline (D137, 230 mg). LCMS: (ES, m/z): 413 [M+H] ⁺ . Synthesis of Intermediate D138 Into an 8 mL vial were added Intermediate D137 (200 mg, 0.484 mmol, 1.0 equiv), tert-butyl piperazine-1-carboxylate (135.34 mg, 0.726 mmol, 1.5 equiv), dioxane (4 mL), XPhos (46.19 mg, 0.097 mmol, 0.2 equiv), Pd ₂ (dba) ₃ (44.36 mg, 0.048 mmol, 0.1 equiv) and Cs ₂ CO ₃ (236.76 mg, 0.726 mmol, 1.5 equiv) at room temperature. The resulting mixture was stirred overnight at 80°C under nitrogen atmosphere and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with CH ₂ Cl ₂ / MeOH (20:1) to afford tert-butyl 4-{4-cyclopropyl-2-[7-fluoro-6-(methoxymethoxy)-2-methylinda zol-5- yl]quinazolin-6-yl}piperazine-1-carboxylate (D138, 160 mg). LCMS: (ES, m/z): 563 [M+H] ⁺ . Into an 8 mL vial were added Intermediate D138 (80 mg, 0.142 mmol, 1 equiv), DCM (1 mL) and TFA (1 mL) at room temperature. The resulting mixture was stirred for 2 h at room temperature and then concentrated under reduced pressure. The residue was purified by reverse flash chromatography following Condition 4, Gradient 4 as previously delineated to afford 5-[4- cyclopropyl-6-(piperazin-1-yl)quinazolin-2-yl]-7-fluoro-2-me thylindazol-6-ol; trifluoroacetic acid (Compound 518, 22 mg). LCMS: (ES, m/z): 418 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 13.85 (s, 1H), 8.87 (s, 2H), 8.77 (s, 1H), 8.55 (d, J = 2.6 Hz, 1H), 7.99 (d, J = 9.3 Hz, 1H), 7.93 (dd, J = 9.3, 2.5 Hz, 1H), 7.79 (d, J = 2.5 Hz, 1H), 4.17 (s, 3H), 3.65 (t, J = 5.1 Hz, 4H), 3.33 (d, J = 6.0 Hz, 4H), 3.22 (tt, J = 8.1, 4.5 Hz, 1H), 1.45 (p, J = 3.9, 3.5 Hz, 2H), 1.35 (dt, J = 8.1, 3.3 Hz, 2H). Example 236: Synthesis of Compound 519 Synthesis of Intermediate D139 To a stirred mixture of Intermediate D120 (310 mg, 1.328 mmol, 1 equiv) and 5-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-thiazole (308.30 mg, 1.461 mmol, 1.1 equiv) in THF (6 mL) were added K ₃ PO ₄ (845.50 mg, 3.984 mmol, 3 equiv) and Pd(dppf)Cl ₂ (97.15 mg, 0.133 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for overnight at 80°C under nitrogen atmosphere and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford 2,6-dichloro-4-(1,3-thiazol-5-yl) quinazoline (D139, 300 mg). LCMS: (ES, m/z): 282 [M+H] ⁺ . Synthesis of Intermediate D140 To a stirred mixture of Intermediate D139 (300 mg, 1.063 mmol, 1 equiv) and 6- (methoxymethoxy)-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-d ioxaborolan-2-yl)indazole (388.56 mg, 1.169 mmol, 1.1 equiv) in dioxane/H ₂ O (10:1; 6.6 mL) were added K ₂ CO ₃ (440.86 mg, 3.189 mmol, 3 equiv) and Pd(dppf)Cl ₂ (77.80 mg, 0.106 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 80°C under nitrogen atmosphere and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford 6- chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]-4-(1, 3-thiazol-5-yl) quinazoline (D140, 210 mg). LCMS: (ES, m/z): 452 [M+H] ⁺ . Synthesis of Intermediate D141 To a stirred mixture of Intermediate D140 (210 mg, 0.465 mmol, 1 equiv) and tert-butyl piperazine-1-carboxylate (129.82 mg, 0.698 mmol, 1.5 equiv) in dioxane (3 mL) were added Cs2CO ₃ (455.60 mg, 1.395 mmol, 3 equiv), X-Phos (44.30 mg, 0.093 mmol, 0.2 equiv) and Pd ₂ (dba) ₃ (42.55 mg, 0.047 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred overnight at 80°C under nitrogen atmosphere and later concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with DCM / MeOH (20:1) to afford tert-butyl 4-{2-[6- (methoxymethoxy)-2,7-dimethylindazol-5-yl]-4-(1,3-thiazol-5- yl) quinazolin-6-yl} piperazine-1- carboxylate (D141, 120 mg). LCMS: (ES, m/z): 602 [M+H] ⁺ . Synthesis of Compound 519 To a stirred solution of Intermediate D141 (120 mg, 0.199 mmol, 1 equiv) in DCM (1 mL) was added TFA (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature and subsequently concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 13, Gradient 3 as previously described to afford 2,7- dimethyl-5-[6-(piperazin-1-yl)-4-(1,3-thiazol-5-yl) quinazolin-2-yl] indazol-6-ol (Compound 519, 29.4 mg). LCMS: (ES, m/z): 458 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d6) δ 13.45 (s, 1H), 9.48 (s, 1H), 8.96 (s, 1H), 8.87 (s, 1H), 8.44 (s, 1H), 8.02 (d, J = 2.8 Hz, 2H), 7.55 (d, J = 1.9 Hz, 1H), 4.15 (s, 3H), 3.36 (t, J = 5.0 Hz, 4H), 2.94 (t, J = 5.1 Hz, 4H), 2.41 (s, 3H). Example 237: Synthesis of Compound 520 Synthesis of Intermediate D143 A solution of 6-bromo-2-chloroquinazoline (D142, 600 mg, 2.464 mmol, 1 equiv) and CH ₃ SNa (259 mg, 3.696 mmol, 1.5 equiv) in DMF (12 mL) was stirred for 3 h at room temperature, quenched by the addition of water (80 mL) at room temperature, and then extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (1 x 5 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (20:1) to afford 6-bromo- 2-(methylsulfanyl)quinazoline (D143, 400 mg). LCMS: (ES, m/z): 255 [M+H] ⁺ . Synthesis of Intermediate D144 To a stirred solution of Intermediate D143 (300 mg, 1.176 mmol, 1 equiv) and tert-butyl piperazine-1-carboxylate (241 mg, 1.294 mmol, 1.1 equiv) in dioxane (10 mL) were added t- BuONa (226 mg, 2.352 mmol, 2 equiv), 1,2,3,4,5-pentaphenyl-1'-(di-tert- butylphosphino)ferrocene (168 mg, 0.235 mmol, 0.2 equiv) and Pd2(dba) ₃ (108 mg, 0.118 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 h at 90°C under nitrogen atmosphere, subsequently allowed to cool to room temperature, and finally concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (4:1) to afford tert-butyl 4-[2- (methylsulfanyl)quinazolin-6-yl]piperazine-1-carboxylate (D144, 220 mg). LCMS: (ES, m/z): 361 [M+H] ⁺ . To a stirred solution of Intermediate D144 (220 mg, 0.610 mmol, 1 equiv) and 6- (methoxymethoxy)-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-d ioxaborolan-2-yl)indazole (203 mg, 0.610 mmol, 1 equiv) in THF (8 mL) were added Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (50 mg, 0.061 mmol, 0.1 equiv) and Copper(I) 3-methylsalicylate (289 mg, 1.342 mmol, 2.2 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 h at 90°C under nitrogen atmosphere, allowed to cool to room temperature, and then concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography following Condition 7, Gradient 5 as previously delineated to afford tert-butyl 4-{2-[6-(methoxymethoxy)-2,7- dimethylindazol-5-yl]quinazolin-6-yl}piperazine-1-carboxylat e (D145, 125 mg). LCMS: (ES, m/z): 519 [M+H] ⁺ . A solution of Intermediate D145 (125 mg, 0.241 mmol, 1 equiv) and 4 M HCl (gas) in 1,4- dioxane (2 mL) in DCM (8 mL) was stirred for 2 h at room temperature and then concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography following Condition 10, Gradient 14 as previously described to afford 2,7-dimethyl-5-[6- (piperazin-1-yl)quinazolin-2-yl]indazol-6-ol (Compound 520, 51 mg). LCMS: (ES, m/z): 375 [M+H] ⁺ . ¹ H NMR: (300 MHz, Methanol-d4) δ λ.42 (s, 1H), 8.λ6 (d, J = 0.8 Hz, 1H), 8.24 (s, 1H), 7.89 (d, J = 2.4 Hz, 2H), 7.34 (s, 1H), 4.20 (s, 3H), 3.43-3.33 (m, 4H), 3.10-3.01 (m, 4H), 2.49 (d, J = 0.7 Hz, 3H), 1.31 (s, 1H). Example 238: Synthesis of Compound 521 Synthesis of Intermediate D146 To a stirred solution of 6-bromo-2-(methylsulfanyl)quinazoline (D143, 260 mg, 1.019 mmol, 1 equiv) and tert-butyl N-methyl-N-[(3R)-pyrrolidin-3-yl]carbamate (307 mg, 1.528 mmol, 1.5 equiv) in dioxane (10 mL) were added t-BuONa (196 mg, 2.038 mmol, 2 equiv), 1,2,3,4,5- pentaphenyl-1'-(di-tert-butylphosphino)ferrocene (145 mg, 0.204 mmol, 0.2 equiv) and Pd2(dba) ₃ (94 mg, 0.102 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 90°C under nitrogen atmosphere, allowed to cool to room temperature, quenched by the addition of water (50 mL) at room temperature, and subsequently extracted with EtOAc (3 x 8 mL). The combined organic layers were washed with brine (1 x 5 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (4:1) to afford tert-butyl N-methyl-N-[(3R)-1-[2-(methylsulfanyl)quinazolin-6-yl]pyrrol idin-3- yl]carbamate (D146, 220 mg). LCMS: (ES, m/z): 375 [M+H] ⁺ . To a stirred solution of Intermediate D146 (220 mg, 0.587 mmol, 1 equiv) and 6- (methoxymethoxy)-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-d ioxaborolan-2-yl)indazole (195 mg, 0.587 mmol, 1 equiv) in THF (6 mL) were added Copper(I) 3-methylsalicylate (278 mg, 1.291 mmol, 2.2 equiv) and Pd(dppf)Cl ₂ .CH ₂ Cl ₂ (48 mg, 0.059 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 12 h at 90°C under nitrogen atmosphere and subsequently concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography following Condition 7, Gradient 5 as previously described to afford tert-butyl N-[(3R)-1-{2-[6-(methoxymethoxy)-2,7- dimethylindazol-5-yl]quinazolin-6-yl}pyrrolidin-3-yl]-N-meth ylcarbamate (D147, 110 mg). LCMS: (ES, m/z): 489 [M+H] ⁺ . A solution of Intermediate D147 (110 mg, 0.225 mmol, 1 equiv) and HCl (gas) in 1,4-dioxane (1 mL) in DCM (5 mL) was stirred for 2 h at room temperature and then concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography following Condition 10, Gradient 26 as previously described to afford 2,7-dimethyl-5-{6-[(3R)-3- (methylamino)pyrrolidin-1-yl]quinazolin-2-yl}indazol-6-ol (Compound 521, 28 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 389 [M+H] ⁺ . ¹ H NMR: (300 MHz, DMSO-d ₆ ) δ 13.70 (s, 1H), λ.47 (s, 1H), 8.86 (s, 1H), 8.38 (s, 1H), 7.λ0 (d, J = 9.1 Hz, 1H), 7.52 (dd, J = 9.3, 2.7 Hz, 1H), 6.93 (d, J = 2.7 Hz, 1H), 4.14 (s, 3H), 3.63-3.38 (m, 4H), 3.19 (dd, J = 9.8, 4.4 Hz, 1H), 2.37 (d, J = 16.8 Hz, 6H), 2.16 (dd, J = 12.6, 6.1 Hz, 1H), 2.05 (s, 1H), 1.88 (dd, J = 11.9, 6.1 Hz, 1H). Example 239: Synthesis of Compound 522 Synthesis of Intermediate D149

Ethyl 6-[4-(tert-butoxycarbonyl) piperazin-1-yl]-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5- yl] quinazoline-4-carboxylate (D148, 210 mg, 0.356 mmol, 1 equiv) was added to a stirred solution of NH ₃ (g) in MeOH (8 mL) at room temperature. The resulting mixture was stirred overnight at 80°C and subsequently concentrated under reduced pressure to afford tert-butyl 4- {4-carbamoyl-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl] quinazolin-6-yl} piperazine-1- carboxylate (D149, 195 mg). LCMS: (ES, m/z): 562 [M+H] ⁺ . Synthesis of Intermediate D150 Intermediate D149 (195 mg, 0.347 mmol, 1 equiv) was added to a stirred solution of (dimethoxymethyl) dimethylamine (4 mL, 0.174 mmol). The resulting mixture was stirred for 2 h at 100°C and then concentrated under reduced pressure to afford tert-butyl 4-(4-{[(1E)- (dimethylamino) methylidene]carbamoyl}-2-[6-(methoxymethoxy)-2,7-dimethylind azol-5- yl]quinazolin-6-yl)piperazine-1-carboxylate (D150, 170 mg). LCMS: (ES, m/z): 617 [M+H] ⁺ . Synthesis of Intermediate D151

To a stirred solution of Intermediate D150 (170 mg, 0.276 mmol, 1 equiv) in AcOH (4 mL) was added hydrazine hydrate (0.2 mL) at room temperature. The resulting mixture was stirred for 1 h at 90°C and later concentrated under reduced pressure. The residue was purified by trituration with ACN (3 mL) to afford tert-butyl 4-[2-(6-hydroxy-2,7-dimethylindazol-5-yl)-4-(4H-1,2,4- triazol-3-yl) quinazolin-6-yl] piperazine-1-carboxylate (D151, 132 mg). LCMS: (ES, m/z): 542 [M+H] ⁺ . Synthesis of Compound 522 To a stirred solution of Intermediate D151 (75 mg, 0.138 mmol, 1 equiv) in DCM (1 mL) was added TFA (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature and then concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 7, Gradient 5 as previously described to afford 2,7-dimethyl-5- [6-(piperazin-1-yl)-4-(4H-1,2,4-triazol-3-yl) quinazolin-2-yl] indazol-6-ol; bis(trifluoroacetic acid) (Compound 522, 39.3 mL). LCMS: (ES, m/z): 441 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 13.53-13.48 (s, 1H), 9.43-9.00 (m, 2H), 8.81 (s, 2H), 8.44 (s, 1H), 8.13-8.01 (m, 2H), 4.17 (s, 3H), 3.60 (d, J = 10.4 Hz, 1H), 3.37 (s, 4H), 2.42 (s, 3H). Example 240: Synthesis of Compound 523

To a stirred solution of Intermediate D149 (85 mg, 0.151 mmol, 1 equiv) in DCM (1 mL) was added TFA (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature and then concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 13, Gradient 6 as previously described to afford 2-(6-hydroxy- 2,7-dimethylindazol-5-yl)-6-(piperazin-1-yl) quinazoline-4-carboxamide (Compound 523, 25.9 mg). LCMS: (ES, m/z): 441 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d6) δ 13.38 (s, 1H), λ.06 (s, 2H), 8.62 (s, 2H), 8.06 (s, 1H), 7.98 (d, J = 2.6 Hz, 2H), 4.16 (s, 3H), 3.31 – 3.23 (m, 4H), 2.90 (t, J = 5.1 Hz, 4H), 2.41 (s, 3H). Example 241: Synthesis of Compound 524 Synthesis of Intermediate D152 To a stirred solution of Intermediate D148 (100 mg, 0.169 mmol, 1 equiv) in MeOH (2 mL) was added LiOH ^. H ₂ O (14.21 mg, 0.338 mmol, 2 equiv) at room temperature. The resulting mixture was stirred overnight at 40°C, then concentrated under vacuum and subsequently diluted with H ₂ O (5 mL) and acidified to pH 6 with HCl (1N). The aqueous layer was extracted with DCM (3 x 100 mL), and the combined organic layers were concentrated under reduced pressure to afford 6-[4-(tert-butoxycarbonyl) piperazin-1-yl]-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5- yl] quinazoline-4-carboxylic acid (D152, 80 mg). LCMS: (ES, m/z): 563 [M+H] ⁺ . Synthesis of Compound 524

To a stirred solution of Intermediate D152 (80 mg, 0.142 mmol, 1 equiv) in DCM (1 mL) was added TFA (1 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature and then concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 13, Gradient 1 as previously described to afford 2-(6-hydroxy- 2,7-dimethylindazol-5-yl)-6-(piperazin-1-yl) quinazoline-4-carboxylic acid (Compound 524, 51.1 mg, 85.88%) as yellow solid. LCMS: (ES, m/z): 419 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d6) δ 13.77 (s, 1H), 10.12 (s, 2H), 8.86 (s, 1H), 8.40 (s, 1H), 7.λ4 (d, J = 1.5 Hz, 2H), 7.47 (s, 1H), 4.14 (s, 3H), 3.59 (d, J = 5.8 Hz, 4H), 3.41 (d, J = 5.6 Hz, 4H), 2.39 (s, 3H). Example 242: Synthesis of Compound 525 Synthesis of Intermediate D153 To a stirred solution of Intermediate D143 (400 mg, 1.568 mmol, 1 equiv) and tert-butyl (2R,6S)-2,6-dimethylpiperazine-1-carboxylate (370 mg, 1.725 mmol, 1.1 equiv) in dioxane (15 mL) were added t-BuONa (302 mg, 3.136 mmol, 2 equiv), 1,2,3,4,5-pentaphenyl-1'-(di-tert- butylphosphino)ferrocene (223 mg, 0.314 mmol, 0.2 equiv) and Pd ₂ (dba) ₃ (144 mg, 0.157 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 4 h at 90°C under nitrogen atmosphere and subsequently allowed to cool to room temperature. The reaction was quenched by the addition of water (80 mL) at room temperature and then extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (1 x 5 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (3:1) to afford tert-butyl (2R,6S)-2,6-dimethyl-4-[2-(methylsulfanyl)quinazolin-6-yl]pi perazine-1- carboxylate (D153, 320 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 389 [M+H] ⁺ . To a stirred solution of Intermediate D153 (320 mg, 0.824 mmol, 1 equiv) and 6- (methoxymethoxy)-2,7-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-d ioxaborolan-2-yl)indazole (274 mg, 0.824 mmol, 1 equiv) in THF (10 mL) were added Copper(I) 3-methylsalicylate (389 mg, 1.813 mmol, 2.2 equiv) and Pd(dppf)Cl ₂ (61 mg, 0.082 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 12 h at 90°C under nitrogen atmosphere, then allowed to cool to room temperature, quenched by the addition of water (50 mL) at room temperature, and extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (1 x 5 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography following Condition 10, Gradient 25 as previously described to afford tert-butyl (2R,6S)-4-{2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]qu inazolin-6-yl}-2,6- dimethylpiperazine-1-carboxylate (D154, 140 mg). LCMS: (ES, m/z): 503 [M+H] ⁺ Synthesis of Compound 525 A solution of Intermediate D154 (130 mg, 0.238 mmol, 1 equiv) and HCl (gas) in 1,4-dioxane (2 mL) in DCM (6 mL) was stirred for 2 h at room temperature and then concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography following Condition 10, Gradient 4 as previously described to afford 5-{6-[(3R,5S)-3,5-dimethylpiperazin- 1-yl]quinazolin-2-yl}-2,7-dimethylindazol-6-ol (Compound 525, 57 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 403 [M+H] ⁺ . ¹ H NMR: (300 MHz, DMSO-d ₆ ) δ 13.64 (s, 1H), λ.52 (s, 1H), 8.λ0 (s, 1H), 8.40 (s, 1H), 8.01-7.87 (m, 2H), 7.39 (d, J = 2.3 Hz, 1H), 4.14 (s, 3H), 3.81 (dd, J = 12.0, 2.8 Hz, 2H), 2.90 (dd, J = 16.7, 2.8 Hz, 2H), 2.43-2.25 (m, 5H), 1.08 (d, J = 6.2 Hz, 6H). Example 243: Synthesis of Compound 526 Synthesis of Intermediate D156 To a stirred solution of 2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]pyrido[3,2- d]pyrimidin-6-ol (D155, 350 mg, 0.996 mmol, 1 equiv) and tert-butyl (2R,6S)-2,6- dimethylpiperazine-1-carboxylate (320 mg, 1.494 mmol, 1.5 equiv) in MeCN (10 mL) were added BOP (881 mg, 1.992 mmol, 2 equiv) and DBU (455 mg, 2.988 mmol, 3 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 24 h at 55°C under nitrogen atmosphere and subsequently allowed to cool to room temperature. The reaction was quenched by the addition of water (50 mL) at room temperature and extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine (1 x 20 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with EA to afford tert-butyl (2R,6S)-4-[2-(6- hydroxy-2,7-dimethylindazol-5-yl)pyrido[3,2-d]pyrimidin-6-yl ]-2,6-dimethylpiperazine-1- carboxylate (D156, 400 mg). LCMS: (ES, m/z): 548 [M+H] ⁺ . Synthesis of Compound 526

A solution of Intermediate D156 (168 mg, 0.307 mmol, 1 equiv) and 4 M HCl(gas)in 1,4- dioxane (1 mL) in DCM (3 mL) was stirred for 1 h at room temperature and then concentrated under vacuum. The residue was purified by reversed-phase flash chromatography following Condition 10, Gradient 24 as previously described to afford 5-{6-[(3R,5S)-3,5- dimethylpiperazin-1-yl]pyrido[3,2-d]pyrimidin-2-yl}-2,7-dime thylindazol-6-ol (Compound 526, 75 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 404 [M+H] ⁺ . ¹ H NMR: (300 MHz, DMSO-d ₆ ) δ 13.2λ (s, 1H), λ.25 (s, 1H), 8.85 (s, 1H), 8.40 (s, 1H), 8.18 (d, J = 9.5 Hz, 1H), 7.81 (d, J = 9.6 Hz, 1H), 4.50 (d, J = 12.4 Hz, 2H), 4.14 (s, 3H), 2.77 (s, 2H), 2.43 (d, J = 23.9 Hz, 5H), 1.08 (d, J = 6.1 Hz, 6H). Example 244: Synthesis of Compound 527 Synthesis of Intermediate D158 To a solution of ethyl 6-chloro-2-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5- yl]quinazoline-4 –carboxylate (D157, 330.0 mg, 0.742 mmol, 1.0 equiv) and tert-butyl (2R,6S)- 2,6-dimethylpiperazine-1-carboxylate (206.6 mg, 0.965 mmol, 1.3 equiv) in dioxane (8 mL) were added Cs2CO ₃ (483.4 mg, 1.484 mmol, 2.0 equiv), Pd2(dba) ₃ (67.9 mg, 0.074 mmol, 0.1 equiv), and XPhos (70.7 mg, 0.148 mmol, 0.2 equiv). After stirring for 3 h at 80°C under a nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (5:1) to afford ethyl 6-[(3R,5S)-4-(tert-butoxycarbonyl)-3,5-dimethylpiperazin-1-y l]-2-[7-fluoro-6- (methoxymethoxy)-2-methylindazol-5-yl]quinazoline-4-carboxyl ate (D158, 350 mg). LCMS: (ES, m/z): 623 [M+H] ⁺ . Into a 40 mL vial were added Intermediate D158 (330.0 mg, 0.530 mmol, 1.0 equiv) and methylamine (2M in methanol) (5 mL) at room temperature. The resulting mixture was stirred for 5 h at 80°C and subsequently concentrated under reduced pressure to afford tert-butyl (2R,6S)-4-{2-[7-fluoro-6-(methoxymethoxy)-2-methylindazol-5- yl]-4- (methylcarbamoyl)quinazolin-6-yl}-2,6-dimethylpiperazine-1-c arboxylate (D159, 320 mg). LCMS: (ES, m/z): 608 [M+H] ⁺ . Synthesis of Compound 527 To a stirred solution of Intermediate D159 (150.0 mg, 0.247 mmol, 1.0 equiv) in DCM (2 mL) was added TFA (0.5 mL) dropwise at room temperature. The resulting mixture was stirred for 1 h at room temperature and then concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 14, Gradient 1 as previously described to afford 6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-2-(7-fluoro-6-hydroxy -2-methylindazol-5-yl)- N-methylquinazoline-4-carboxamide (Compound 527, 53 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 464 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 13.42 (s, 1H), λ.23 (d, J = 5.1 Hz, 1H), 9.04 (d, J = 0.9 Hz, 1H), 8.57 (d, J = 2.5 Hz, 1H), 8.17 (t, J = 1.7 Hz, 1H), 8.01 (d, J = 1.6 Hz, 2H), 4.19 (s, 3H), 3.77 (dd, J = 11.9, 2.8 Hz, 2H), 2.97 (d, J = 4.6 Hz, 3H), 2.90 (ddd, J = 9.8, 6.1, 2.9 Hz, 2H), 2.34 (t, J = 11.1 Hz, 2H), 1.09 (d, J = 6.3 Hz, 6H). Example 245: Synthesis of Compound 531 A mixture of ethyl 6-chloro-2-[6-(methoxymethoxy)-2-methylindazol-5-yl]quinazol ine-4- carboxylate (D160, 200 mg, 0.469 mmol, 1 equiv), tert-butyl (2R,6S)-2,6-dimethylpiperazine-1- carboxylate (150 mg, 0.704 mmol, 1.50 equiv), Pd2(dba) ₃ (43 mg, 0.047 mmol, 0.10 equiv), RuPhos (44 mg, 0.094 mmol, 0.2 equiv) and Cs ₂ CO ₃ (383 mg, 1.174 mmol, 2.00 equiv) in dioxane (5 mL) was stirred for 2 h at 80°C under nitrogen atmosphere, allowed to cool to room temperature, and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE/EA (1:1) to afford ethyl 6-[(3R,5S)-4-(tert- butoxycarbonyl)-3,5-dimethylpiperazin-1-yl]-2-[6-(methoxymet hoxy)-2-methylindazol-5- yl]quinazoline-4-carboxylate (D161, 170 mg). LCMS: (ES, m/z): 605 [M+H] ⁺ . A mixture of 2 M CH ₃ NH ₂ in MeOH (0.5 mL) was treated with Intermediate D161 (50 mg, 0.083 mmol, 1 equiv) for 1 h at 80°C and subsequently concentrated under reduced pressure to afford tert-butyl (2R,6S)-4-{2-[6-(methoxymethoxy)-2-methylindazol-5-yl]-4- (methylcarbamoyl)quinazolin-6-yl}-2,6-dimethylpiperazine-1-c arboxylate, (D162, 45 mg, crude) which was used directly in the next step without further purification. LCMS: (ES, m/z): 590 [M+H] ⁺ . Synthesis of Compound 531 A solution of TFA (0.15 mL) in DCM (0.5 mL) was treated with Intermediate D162 (40 mg, 0.068 mmol, 1 equiv) for 15 min at room temperature and then concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography following Condition 9, Gradient 9 as previously described to afford 6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-2-(6- hydroxy-2-methylindazol-5-yl)-N-methylquinazoline-4-carboxam ide (Compound 531, 13 mg). Absolute stereochemistry of the compound was arbitrarily assigned .LCMS: (ES, m/z): 446 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 13.22 (s, 1H), λ.22 (d, J = 8.0 Hz, 2H), 8.44 (s, 1H), 8.16 (d, J = 2.4 Hz, 1H), 8.06-7.93 (m, 2H), 6.91 (s, 1H), 4.14 (s, 3H), 3.93-3.65 (m, 2H), 2.97 (d, J = 4.8 Hz, 3H), 2.90 (s, 2H), 2.32 (t, J = 11.0 Hz, 2H), 1.09 (d, J = 6.2 Hz, 6H). Example 246: Synthesis of Compound 534 Synthesis of Intermediate D164 To a stirred mixture of ethyl 6-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5- yl]pyrido[3,2-d]pyrimidine-4-carboxylate (D163, 120 mg, 0.272 mmol, 1.0 equiv) and tert-butyl (2R,6S)-2,6-dimethylpiperazine-1-carboxylate (67.6 mg, 0.316 mmol, 1.0 equiv) in DMAc (2 mL) was added TEA (95.8 mg, 0.948 mmol, 3.0 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 h at 60°C under nitrogen atmosphere, allowed to cool to room temperature, and subsequently concentrated under reduced pressure. The crude resulting mixture (D164) was used in the next step directly without further purification. LCMS: (ES, m/z): 620 [M+H] ⁺ . To the above crude was added CH ₃ NH ₂ (1.5 mL, 2M in MeOH) in MeOH (10 mL) at room temperature. The resulting mixture was stirred for an additional 3 h at 80°C, allowed to cool to room temperature, and extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with water (1 x 10mL) and brine (1 x 10 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by Prep-TLC (EA) to afford tert-butyl (2R,6S)-4-{2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]-4 - (methylcarbamoyl)pyrido[3,2-d]pyrimidin-6-yl}-2,6-dimethylpi perazine-1-carboxylate (D165, 121 mg). LCMS: (ES, m/z): 577 [M+H] ⁺ . Synthesis of Compound 534 A solution of Intermediate D165 (121 mg, 0.200 mmol, 1.0 equiv) in DCM (1 mL) was treated with TFA (0.25 mL) at room temperature. The resulting mixture was stirred for 1 h at room temperature under nitrogen atmosphere and then concentrated under reduced pressure. The crude product was purified by Prep-HPLC following Condition 6, Gradient 18 as previously described to afford 6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-2-(6-hydroxy-2,7-dime thylindazol-5-yl)-N- methylpyrido[3,2-d]pyrimidine-4-carboxamide (Compound 534, 60.2 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 461 [M+H] ⁺ . ¹ H NMR: (300 MHz, DMSO-d6) δ 13.25 (s, 1H), 8.87 (d, J = 4.9 Hz, 1H), 8.60 (d, J = 9.5 Hz, 1H), 8.45 (s, 1H), 8.36 (s, 1H), 8.06 (d, J = 9.3 Hz, 1H), 4.72 (d, J = 12.3 Hz, 2H), 4.14 (s, 3H), 2.92 (d, J = 4.7 Hz, 3H), 2.74 (d, J = 8.3 Hz, 2H), 2.48 (d, J = 2.8 Hz, 2H), 2.37 (s, 3H), 1.08 (d, J = 6.2 Hz, 6H). Example 247: Synthesis of Compound 535 Synthesis of Intermediate D129 To a stirred mixture of ethyl 6-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5- yl]quinazoline-4-carboxylate (D116, 600 mg, 1.361 mmol, 1 equiv) and tert-butyl (2R,6S)-2,6- dimethylpiperazine-1-carboxylate (437 mg, 2.039 mmol, 1.50 equiv) in dioxane (12 mL) were added RuPhos (127 mg, 0.272 mmol, 0.20 equiv), Pd2(dba) ₃ (125 mg, 0.137 mmol, 0.10 equiv) and Cs ₂ CO ₃ (890 mg, 2.732 mmol, 2.01 equiv) in portions. The resulting mixture was stirred for 4 h at 80°C under nitrogen atmosphere and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography and eluted with PE / EA (1:1) to afford ethyl 6-[(3R,5S)-4-(tert-butoxycarbonyl)-3,5-dimethylpiperazin-1-y l]-2-[6- (methoxymethoxy)-2,7-dimethylindazol-5-yl]quinazoline-4-carb oxylate (D129, 580 mg). LCMS: (ES, m/z): 619 [M+H] ⁺ . Synthesis of Intermediate D166

A mixture of Intermediate D129 (100 mg, 0.162 mmol, 1 equiv) and 2M EtNH ₂ in EtOH was stirred for 2 h at 80 °C and then concentrated under reduced pressure to afford tert-butyl (2R,6S)- 4-[4-(ethylcarbamoyl)-2-[6-(methoxymethoxy)-2,7-dimethylinda zol-5-yl]quinazolin-6-yl]-2,6- dimethylpiperazine-1-carboxylate (D166, 85 mg, crude), which was used in the next step directly without further purification . LCMS: (ES, m/z): 618 [M+H] ⁺ . A solution of Intermediate D166 (80 mg, 0.130 mmol, 1 equiv) in DCM (0.8 mL) was treated with 4 M HCl (gas) in 1,4-dioxane (0.4 mL) for 1 h at room temperature and later concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography following Condition 9, Gradient 5 as previously described to afford 6-[(3R,5S)-3,5- dimethylpiperazin-1-yl]-N-ethyl-2-(6-hydroxy-2,7-dimethylind azol-5-yl)quinazoline-4- carboxamide (Compound 535, 52.9 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 474 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 13.41 (s, 1H), 9.24 (t, J = 5.9 Hz, 1H), 9.05 (s, 1H), 8.43 (s, 1H), 8.00 (dd, J = 4.3, 2.4 Hz, 3H), 4.16 (s, 3H), 3.82-3.71 (m, 2H), 3.55-3.42 (m, 2H), 2.99-2.82 (m, 2H), 2.41 (s, 3H), 2.33 (t, J = 11.0 Hz, 2H), 1.26 (t, J = 7.2 Hz, 3H), 1.08 (d, J = 6.2 Hz, 6H). Example 248: Synthesis of Compound 537 Synthesis of Intermediate D167

To a solution of ethyl 6-chloro-2-[6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]quin azoline-4- carboxylate (D116, 200 mg, 0.454 mmol, 1 equiv) and tert-butyl N-methyl-N-[(3S)-pyrrolidin-3- yl]carbamate (136 mg, 0.681 mmol, 1.5 equiv) in dioxane (4 mL) were added Cs ₂ CO ₃ (103 mg, 1.362 mmol, 3.0 equiv), RuPhos (42 mg, 0.091 mmol, 0.2 equiv) and Pd ₂ (dba) ₃ (41 mg, 0.045 mmol, 0.1 equiv). After stirring for 1 h at 90°C under a nitrogen atmosphere, the resulting mixture was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography following Condition 10, Gradient 8 as previously described to afford ethyl 6-[(3S)-3-[(tert-butoxycarbonyl)(methyl)amino]pyrrolidin-1-y l]-2-[6-(methoxymethoxy)-2,7- dimethylindazol-5-yl]quinazoline-4-carboxylate (D167, 180 mg). LCMS: (ES, m/z): 591 [M- Et+Me+H] ⁺ . A solution of Intermediate D167 (180 mg, 0.298 mmol, 1 equiv) in CH ₃ NH ₂ in MeOH (4 mL) was stirred for 1 h at 80°C and subsequently concentrated under reduced pressure to afford tert-butyl (S)-(1-(2-(6-(methoxymethoxy)-2,7-dimethyl-2H-indazol-5-yl)- 4- (methylcarbamoyl)quinazolin-6-yl)pyrrolidin-3-yl)(methyl)car bamate (D168, 190 mg, crude), which was used in the next step directly without further purification. LCMS: (ES, m/z): 590 [M+H] ⁺ . Synthesis of Compound 537 A solution of Intermediate D168 (150 mg, 0.254 mmol, 1 equiv) and 4M HCl (gas) in 1,4- dioxane (4 mL) was stirred for 1 h at room temperature and then concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography following Condition 10, Gradient 9 as previously described to afford 2-(6-hydroxy-2,7-dimethylindazol-5-yl)-N- methyl-6-[(3S)-3-(methylamino)pyrrolidin-1-yl]quinazoline-4- carboxamide (Compound 537, 52 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 446 [M+H] ⁺ . ¹ H NMR: (300 MHz, DMSO-d ₆ ) δ 13.48 (s, 1H), λ.15 (d, J = 4.9 Hz, 1H), 9.05 (s, 1H), 8.40 (s, 1H), 7.98 (d, J = 9.2 Hz, 1H), 7.73 (d, J = 2.7 Hz, 1H), 7.59 (dd, J = 9.3, 2.7 Hz, 1H), 4.16 (s, 3H), 3.65-3.43 (m, 4H), 3.23 (dd, J = 10.1, 4.2 Hz, 1H), 2.96 (d, J = 4.8 Hz, 3H), 2.39 (d, J = 8.0 Hz, 6H), 2.19 (dd, J = 12.8, 6.3 Hz, 1H), 1.99-1.89 (m, 1H). Example 249: Synthesis of Compound 539 A solution of propan-2-amine (1 mL) in EtOH (2 mL) was treated with ethyl 6-[(3R,5S)-4-(tert- butoxy-carbonyl)-3,5-dimethylpiperazin-1-yl]-2-[6-(methoxyme thoxy)-2,7-dimethylindazol-5- yl]quinazoline-4-carboxylate (D129, 100 mg, 0.162 mmol, 1 equiv) for 1 h at 80°C and then allowed to cool to room temperature. The resulting mixture was concentrated under reduced pressure to afford tert-butyl (2R,6S)-4-[4-(isopropylcarbamoyl)-2-[6-(methoxymethoxy)-2,7- dimethylindazol-5-yl]quinazolin-6-yl]-2,6-dimethylpiperazine -1-carboxylate (D169, 95 mg). LCMS: (ES, m/z): 632 [M+H] ⁺ . A solution of Intermediate D169 (95 mg, 0.150 mmol, 1 equiv) in DCM (2 mL) was treated with 4 M HCl (gas) in 1,4-dioxane (0.5 mL) for 1 h at room temperature and subsequently concentrated under reduced pressure. The crude product was purified by reversed-phase flash chromatography following Condition 9, Gradient 5 as previously described to afford 6-[(3R,5S)- 3,5-dimethylpiperazin-1-yl]-2-(6-hydroxy-2,7-dimethylindazol -5-yl)-N-isopropylquinazoline-4- carboxamide (Compound 539, 68.1 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 488 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d6) δ 13.40 (s, 1H), 9.12-8.84 (m, 2H), 8.45 (s, 1H), 8.00 (d, J = 2.4 Hz, 2H), 7.66 (s, 1H), 4.40-4.20 (m, 1H), 4.14 (s, 3H), 3.75 (d, J = 11.5 Hz, 2H), 2.92 (s, 2H), 2.41 (s, 3H), 2.34 (t, J = 10.9 Hz, 2H), 1.30 (d, J = 6.5 Hz, 6H), 1.08 (d, J = 6.4 Hz, 6H). Example 250: Synthesis of Compound 540 Synthesis of Intermediate D170 A solution of cyclobutylamine (0.5 mL) in EtOH (2 mL) was treated with Intermediate D129 (100 mg, 0.162 mmol, 1 equiv) for 1 h at 80°C, allowed to cool to room temperature, and then concentrated under reduced pressure to afford tert-butyl (2R,6S)-4-[4-(cyclobutylcarbamoyl)-2- [6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]quinazolin-6-yl ]-2,6-dimethylpiperazine-1- carboxylate (D170, 90 mg, 86.50%). LCMS: (ES, m/z): 644 [M+H] ⁺ . Synthesis of Compound 540 A solution of Intermediate D170 (90 mg, 0.140 mmol, 1 equiv) in DCM (1.2 mL) was treated with 4 M HCl (gas) in 1,4-dioxane (0.4 mL) for 1 h at room temperature and then concentrated under reduced pressure. The crude product was purified by reversed-phase flash chromatography following Condition 9, Gradient 5 as previously described to afford 6-[4-(azetidin-1-yl)piperidin- 1-yl]-2-(6-hydroxy-2,7-dimethylindazol-5-yl)-N-methylquinazo line-4-carboxamide (Compound 540, 53.9 mg). Absolute stereochemistry of the compound was arbitrarily assigned. LCMS: (ES, m/z): 500 [M+H] ⁺ . ¹ H NMR: (400 MHz, DMSO-d ₆ ) δ 13.3λ (s, 1H), λ.34 (d, J = 8.0 Hz, 1H), 9.01 (s, 1H), 8.45 (s, 1H), 8.00 (d, J = 2.0 Hz, 2H), 7.76 (s, 1H), 4.59 (h, J = 8.4 Hz, 1H), 4.16 (s, 3H), 3.76 (d, J = 11.5 Hz, 2H), 2.93 (s, 2H), 2.41 (s, 3H), 2.40-2.31 (m, 4H), 2.30-2.21 (m, 2H), 1.85-1.69 (m, 2H), 1.09 (d, J = 6.2 Hz, 6H). Example 251: Synthesis of Compound 541 Synthesis of Intermediate D171 To a stirred solution of Intermediate D116 (0.63 g, 3.402 mmol, 1.5 equiv) in dioxane (20 mL) were added XPhos (0.22 g, 0.454 mmol, 0.2 equiv) and Pd2(dba) ₃ (0.21 g, 0.227 mmol, 0.1 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 h at 80°C under nitrogen atmosphere, allowed to cool to room temperature, quenched by the addition of water (100 mL) at room temperature, and then extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine (1 x 50 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography following Condition 9, Gradient 8 as previously described to afford ethyl 6-[4-(tert-butoxycarbonyl)piperazin-1-yl]-2-[6- (methoxymethoxy)-2,7-dimethylindazol-5-yl]quinazoline-4-carb oxylate (D171, 1.1 g). LCMS: (ES, m/z): 591 [M+H] ⁺ . Synthesis of Intermediate D172 A solution of Intermediate D171 (600 mg, 1.016 mmol, 1 equiv) in 9 M NH ₃ (g) in MeOH (150 mL) was stirred for 24 h at 110°C, allowed to cool to room temperature and subsequently concentrated under vacuum. The residue was purified by reversed-phase flash chromatography following Condition 9, Gradient 7 as previously described to afford tert-butyl 4-{4-carbamoyl-2- [6-(methoxymethoxy)-2,7-dimethylindazol-5-yl]quinazolin-6-yl }piperazine-1-carboxylate (D172, 454 mg). LCMS: (ES, m/z): 562 [M+H] ⁺ . Synthesis of Intermediate D173 To a stirred solution of Intermediate D172 (450 mg, 0.801 mmol, 1 equiv) and pyridine (76 mg, 0.961 mmol, 1.2 equiv) in dioxane (10 mL) was added TFAA (337 mg, 1.602 mmol, 2 equiv) dropwise at 0°C under nitrogen atmosphere. The resulting mixture was stirred for 1 h at room temperature under nitrogen atmosphere, quenched by the addition of water (30 mL) at room temperature, and then extracted with EtOAc (3 x 20 mL). The combined organics were washed with brine (1 x 30 mL), dried over anhydrous Na ₂ SO4, and the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography following Condition 9, Gradient 6 as previously described to afford tert-butyl 4-{4-cyano-2-[6- (methoxymethoxy)-2,7-dimethylindazol-5-yl]quinazolin-6-yl}pi perazine-1-carboxylate (D173, 145 mg). LCMS: (ES, m/z): 544 [M+H] ⁺ . Synthesis of Intermediate D174 To a stirred solution of Intermediate D173 (360 mg, 0.662 mmol, 1 equiv) and NH ₄ Cl (106 mg, 1.986 mmol, 3 equiv) in DMF (5 mL) was added NaN3 (129 mg, 1.986 mmol, 3 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 24 h at 80°C under nitrogen atmosphere and allowed to cool to room temperature. The reaction was quenched by the addition of water (20 mL) at room temperature and then extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (1 x 10 mL), dried over anhydrous Na ₂ SO ₄ , and the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography following Condition 10, Gradient 23 as previously described to afford tert-butyl 4-{2-[6-(methoxymethoxy)-2,7-dimethylindazol- 5-yl]-4-(2H-1,2,3,4-tetrazol-5-yl)quinazolin-6-yl}piperazine -1-carboxylate (D174, 230 mg). LCMS: (ES, m/z): 587 [M+H] ⁺ . Synthesis of Compound 541