Compounds and methods for modulating nucleic acid splicing - Patents.com

Abstract

The disclosure features, inter alia, compounds and related compositions that modulate nucleic acid splicing, eg, pre-mRNA splicing, and methods of their use.

Description

[Technical Field]

[0001] Priority claims This application claims priority to U.S. Patent Application No. 63 / 255,178, filed October 13, 2021, U.S. Patent Application No. 63 / 255,348, filed October 13, 2021, U.S. Patent Application No. 63 / 255,079, filed October 13, 2021, U.S. Patent Application No. 63 / 393,208, filed July 28, 2022, and U.S. Patent Application No. 63 / 393,210, filed July 28, 2022. The disclosures of each of the foregoing applications are incorporated herein by reference in their entirety. [Background technology]

[0002] In higher eukaryotic cells, alternative splicing is a major source of protein diversity and is often regulated in tissue- or developmental stage-specific ways. Disease-associated alternative splicing patterns in pre-mRNAs are often mapped to alterations in splice site signals or sequence motifs and regulatory splicing factors (Faustino and Cooper (2003), Genes Dev 17(4):419-37). Current therapeutic approaches for regulating RNA expression include oligonucleotide targeting and gene therapy, but each of these modalities presents its own challenges. Therefore, new technologies for regulating RNA expression, including the development of small molecule compounds that target splicing, are needed. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Faustino and Cooper(2003),Genes Dev 17(4):419-37 Summary of the Invention

[0004] The present disclosure features, inter alia, compounds and related compositions that modulate nucleic acid splicing, e.g., pre-mRNA splicing, and methods of their use. In one embodiment, the compounds described herein are compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers thereof: Accordingly, the present disclosure provides methods for using compounds of the present disclosure (e.g., compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers thereof), and compositions thereof, to target, and in embodiments, bind to or complex with, for example, nucleic acids (e.g., pre-mRNA or small nuclear ribonucleoproteins (snRNPs) or nucleic acid components of the spliceosome), proteins (e.g., snRNPs or protein components of the spliceosome, e.g., members of the splicing machinery, e.g., one or more of U1, U2, U4, U5, U6, U11, U12, U4atac, U6atac snRNPs), or combinations thereof. In another aspect, the compounds described herein can be used to alter the composition or make-up of a nucleic acid (e.g., a pre-mRNA or an mRNA (e.g., a pre-mRNA and an mRNA resulting from the pre-mRNA), for example, by increasing or decreasing splicing at a splice site. In some embodiments, increasing or decreasing splicing modulates the level of a gene product (e.g., RNA or protein) produced. In another aspect, the compounds described herein can 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), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, and stereoisomers thereof) and compositions thereof are used for the prevention and / or treatment of a proliferative disease, disorder, or condition in a subject (e.g., a disease, disorder, or condition characterized by unwanted cell proliferation, e.g., cancer or benign neoplasm). In some embodiments, the compounds described herein (e.g., compounds of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX) 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), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers thereof) and compositions thereof are used for the prevention and / or treatment of a nervous system disease or disorder, an autoimmune disease or disorder, an 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 kidney disease or disorder, or an infectious disease in a subject.

[0005] In one aspect, the present disclosure provides a compound of formula (I): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , Y, R 2 , R 3, m, n, and each of its subvariables are defined as described herein.

[0006] In another aspect, the present disclosure provides a compound of formula (II): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , W, X, Y, Z, R 2 , and each of its subvariables are defined as described herein.

[0007] In another aspect, the present disclosure provides a compound of formula (III): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , X, Y, Z, R 2 , R 7a , R 7b , and each of its subvariables are defined as described herein.

[0008] In another aspect, the present disclosure provides a compound of formula (IV): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , W, X, R 2a , R 2b , R 2c , and each of its subvariables are defined as described herein.

[0009] In another aspect, the present disclosure provides a compound of formula (V): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , W, X, Y, R 2 , and each of its subvariables are defined as described herein.

[0010] In another aspect, the present disclosure provides a compound of formula (VI): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , W, X, R 2a , R 2b , R 2c , and each of its subvariables are defined as described herein.

[0011] In another aspect, the present disclosure provides a compound of formula (VII): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , R 2a , R 2b , R 2c , and each of its subvariables are defined as described herein.

[0012] In another aspect, the present disclosure provides a compound of formula (VIII): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , W, X, Y, Z, R2 , R 7 , and each of its subvariables are defined as described herein.

[0013] In another aspect, the present disclosure provides a compound of formula (IX): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , X, Y, Z, R 2 , R 7b , and each of its subvariables are defined as described herein.

[0014] In another aspect, the present invention provides pharmaceutical compositions comprising a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, and optionally a pharmaceutically acceptable excipient. In one embodiment, the pharmaceutical compositions described herein comprise an effective amount (e.g., a therapeutically effective amount) of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0015] In another aspect, the disclosure provides methods for modulating splicing, e.g., splicing of nucleic acids (e.g., DNA or RNA, e.g., pre-mRNA), with a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another aspect, the disclosure provides compositions for use in modulating splicing, e.g., splicing of nucleic acids (e.g., DNA or RNA, e.g., pre-mRNA), with a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. Modulation of splicing can include affecting any step involved in splicing, including events upstream or downstream of the splicing event. For example, in some embodiments, a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX) binds to a target, e.g., a target nucleic acid (e.g., DNA or RNA, e.g., precursor RNA, e.g., pre-mRNA), a target protein, or a combination thereof (e.g., snRNP and pre-mRNA). A target can include a splice site in pre-mRNA or a component of the splicing machinery, such as the U1 snRNP. In some embodiments, a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX) modifies a target nucleic acid (e.g., DNA or RNA, e.g., precursor RNA, e.g., pre-mRNA), a target protein, or a combination thereof.In some embodiments, a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX) 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., in the absence of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), e.g., a healthy or diseased cell or tissue). In some embodiments, the presence of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX) increases or decreases transcription of a target nucleic acid (e.g., 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., a healthy or diseased cell or tissue in the absence of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX)).

[0016] In another aspect, the disclosure provides methods for preventing and / or treating a disease, disorder, or condition in a subject by administering a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or related composition. In some embodiments, the disease or disorder involves undesired or aberrant splicing. In some embodiments, the disease or disorder is a proliferative disease, disorder, or condition. Exemplary proliferative diseases include cancer, benign neoplasms, or angiogenesis. In other embodiments, the disclosure provides methods for treating and / or preventing a non-proliferative disease, disorder, or condition. In yet other embodiments, the present disclosure provides methods for treating and / or preventing a nervous system disease or disorder, an autoimmune disease or disorder, an 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 kidney disease or disorder, or an infectious disease.

[0017] In another aspect, the disclosure provides a method of downregulating the expression (e.g., level or rate of production) of a target protein in a biological sample or a subject with a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another aspect, the disclosure provides a method of upregulating the expression (e.g., level or rate of production) of a target protein in a biological sample or a subject with a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another aspect, the present disclosure provides a method for modifying a target protein isoform in a biological sample or a subject with a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. Another aspect of the present disclosure relates to a method for inhibiting the activity of a target protein in a biological sample or a subject. In some embodiments, administering a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX) to a biological sample, cell, or subject comprises inhibiting cell growth or inducing cell death.

[0018] In another aspect, the disclosure provides compositions for use in preventing and / or treating a disease, disorder, or condition in a subject by administering a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or related compositions. In some embodiments, the disease or disorder involves undesired or aberrant splicing. In some embodiments, the disease or disorder is a proliferative disease, disorder, or condition. Exemplary proliferative diseases include cancer, benign neoplasms, or angiogenesis. In other embodiments, the disclosure provides methods for treating and / or preventing non-proliferative diseases, disorders, or conditions. In yet other embodiments, the present disclosure provides compositions for use in the treatment and / or prevention of a nervous system disease or disorder, an autoimmune disease or disorder, an 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 kidney disease or disorder, or an infectious disease.

[0019] In another aspect, the disclosure provides a composition for use in down-regulating the expression (e.g., level or rate of production) of a target protein in a biological sample or a subject with a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another aspect, the disclosure provides a composition for use in up-regulating the expression (e.g., level or rate of production) of a target protein in a biological sample or a subject with a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another aspect, the present disclosure provides compositions for use in modifying a target protein isoform in a biological sample or a subject with a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. Another aspect of the disclosure relates to compositions for use in inhibiting the activity of a target protein in a biological sample or a subject. In some embodiments, administering a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX) to a biological sample, cell, or subject includes inhibiting cell growth or inducing cell death.

[0020] In another aspect, the disclosure features a kit including a container containing a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), 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 Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer thereof, or pharmaceutical composition thereof.

[0021] In all aspects of the disclosure, in some embodiments, the compounds described herein, target nucleic acids (e.g., DNA, RNA, e.g., pre-mRNA), or target proteins can be prepared using methods described in U.S. Patent No. 8,729,263, U.S. Patent Publication No. 2015 / 0005289, WO2014 / 028459, WO2016 / 128343, WO2016 / 196386, WO2017 / 100726, WO2018 / 232039, WO2018 / 098446, WO2019 / 028440, WO2019 / 060917, WO2019 / 199972, and WO2020 / 004594, a target nucleic acid (e.g., DNA, RNA, e.g., pre-mRNA), or a target protein other than the compound, target nucleic acid (e.g., DNA, RNA, e.g., pre-mRNA), or target protein described in one of WO2019 / 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 in one of U.S. Patent No. 8,729,263, U.S. Patent Publication No. 2015 / 0005289, WO2014 / 028459, WO2016 / 128343, WO2016 / 196386, WO2017 / 100726, WO2018 / 232039, WO2018 / 098446, WO2019 / 028440, WO2019 / 060917, WO2019 / 199972, and WO2020 / 004594, each of which is incorporated by reference in its entirety.

[0022] 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, examples, and claims. DETAILED DESCRIPTION OF THE INVENTION

[0023] Selected Chemical Definitions Definitions of specific functional groups and chemical terms are described in more detail below. Chemical elements are listed in the CAS version of the Periodic Table of the Elements (Handbook of Chemistry and Physics, 75 th In addition, general principles of organic chemistry and specific functional moieties and reactivities are described in detail in the following texts: 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.

[0024] The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulae depicted herein are constructed according to the standard rules of chemical valency known in the chemical arts.

[0025] When a range of values ​​is listed, it is intended to encompass each value and subrange within the range. For example, "C1-C6 alkyl" is intended to include C1, C2, C3, C4, C5, C6, C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, C2-C6, C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6 alkyl.

[0026] The following terms are intended to have the meanings indicated below and are useful in understanding the description and intended scope of the present invention.

[0027] As used herein, "alkyl" refers to the radical of a straight or branched chain saturated hydrocarbon group having from 1 to 24 carbon atoms ("C1-C 24 In some embodiments, an alkyl group has 1 to 12 carbon atoms ("C-C 12 In some embodiments, an alkyl group has 1 to 8 carbon atoms ("C1-C8 alkyl"). In some embodiments, an alkyl group has 1 to 6 carbon atoms ("C1-C6 alkyl"). In some embodiments, an alkyl group has 2 to 6 carbon atoms ("C2-C6 alkyl"). In some embodiments, an alkyl group has 1 carbon atom ("C1 alkyl"). Examples of C1-C6 alkyl groups include methyl (C1), ethyl (C2), n-propyl (C3), isopropyl (C3), n-butyl (C4), tert-butyl (C4), sec-butyl (C4), isobutyl (C4), n-pentyl (C5), 3-pentanyl (C5), amyl (C5), neopentyl (C5), 3-methyl-2-butanyl (C5), tertiary amyl (C5), and n-hexyl (C6). Additional examples of alkyl groups include n-heptyl (C7), n-octyl (C8), and the like. Each example of an alkyl group can independently be optionally substituted, i.e., it can be unsubstituted (an "unsubstituted alkyl") or substituted with one or more substituents, e.g., 1 to 5 substituents, 1 to 3 substituents, or 1 substituent (a "substituted alkyl"). In certain embodiments, an alkyl group can be an unsubstituted C 1- C 10 In certain embodiments, the alkyl group is a substituted C 1- It is a C6 alkyl.

[0028] As used herein, "alkenyl" refers to the radical of a straight or branched chain hydrocarbon group having 2 to 24 carbon atoms, one or more carbon-carbon double bonds and no triple bonds ("C2-C 24 In some embodiments, an alkenyl group has 2 to 10 carbon atoms ("C-C 10 In some embodiments, an alkenyl group has 2 to 8 carbon atoms ("C2-C8 alkenyl"). In some embodiments, an alkenyl group has 2 to 6 carbon atoms ("C2-C6 alkenyl"). In some embodiments, an alkenyl group has 2 carbon atoms ("C2 alkenyl"). The one or more carbon-carbon double bonds can be internal (such as 2-butenyl) or terminal (such as 1-butenyl). Examples of C2-C4 alkenyl groups include ethenyl (C2), 1-propenyl (C3), 2-propenyl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), and the like. Examples of C2-C6 alkenyl groups include the aforementioned C 2-4 In addition to alkenyl groups, examples include pentenyl (C5), pentadienyl (C5), hexenyl (C6), and the like. Additional examples of alkenyl include heptenyl (C7), octenyl (C8), octatrienyl (C8), and the like. Each example of an alkenyl group can independently be optionally substituted, i.e., it can be unsubstituted (an "unsubstituted alkenyl") or substituted with one or more substituents, e.g., 1 to 5 substituents, 1 to 3 substituents, or 1 substituent (a "substituted alkenyl"). In certain embodiments, an alkenyl group can be an unsubstituted C 1- C 10 In certain embodiments, the alkenyl group is a substituted C 2- It is a C6 alkenyl.

[0029] As used herein, the term "alkynyl" refers to a radical of a straight- or branched-chain hydrocarbon group having 2 to 24 carbon atoms and one or more carbon-carbon triple bonds ("C2-C 24In some embodiments, an alkynyl group has 2 to 10 carbon atoms ("C-C 10 In some embodiments, an alkynyl group has 2 to 8 carbon atoms ("C2-C8 alkynyl"). In some embodiments, an alkynyl group has 2 to 6 carbon atoms ("C2-C6 alkynyl"). In some embodiments, an alkynyl group has 2 carbon atoms ("C2 alkynyl"). The one or more carbon-carbon triple bonds can be internal (such as 2-butynyl) or terminal (such as 1-butynyl). Examples of C2-C4 alkynyl groups include ethynyl (C2), 1-propynyl (C3), 2-propynyl (C3), 1-butynyl (C4), 2-butynyl (C4), and the like. Each instance of alkynyl can independently be optionally substituted, i.e., it can be unsubstituted ("unsubstituted alkynyl") or substituted with one or more substituents, e.g., 1 to 5 substituents, 1 to 3 substituents, or 1 substituent ("substituted alkynyl"). In certain embodiments, the alkynyl group is an unsubstituted C 2-10 In certain embodiments, the alkynyl group is a substituted C 2-6 It is alkynyl.

[0030] As used herein, the term "haloalkyl" refers to a stable acyclic straight or branched chain, or combination thereof, containing 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 can be located at any position of the haloalkyl group. Exemplary haloalkyl groups include -CF3, -CCl3, -CH2-CF3, -CH2-CCl 3、 -CH2-CBr 3、 -CH2-CI 3、Examples of haloalkyl include, but are not limited to, -CH2-CH2-CH(CF3)-CH3, -CH2-CH2-CH(Br)-CH3, and -CH2-CH=CH-CH2-CF3. Each instance of haloalkyl can independently be optionally substituted, i.e., it can be unsubstituted (an "unsubstituted haloalkyl") or substituted with one or more substituents, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent (a "substituted haloalkyl").

[0031] As used herein, the term "heteroalkyl" refers to a stable acyclic straight or branched chain, or combination thereof, containing at least one carbon atom and at least one heteroatom selected from the group consisting of O, N, P, Si, and S, where the nitrogen and sulfur atoms can be optionally oxidized and the nitrogen heteroatom can be optionally quaternized. The heteroatom(s) O, N, P, S, and Si can be located at any position of the heteroalkyl group. Exemplary heteroalkyl groups include, but are not limited to, -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -CH2-CH2, -S(O)-CH3, -CH2-CH2-S(O)-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3, -CH=CH-N(CH3)-CH3, -O-CH3, and -O-CH2-CH3. Up to two or three heteroatoms may be consecutive, such as, for example, -CH2-NH-OCH3 and -CH2-O-Si(CH3)3. "Heteroalkyl" is listed followed by -CHO, -NR C R D When specific heteroalkyl groups such as -CH2O or -NR2 are recited, the term heteroalkyl and -CH2O or -NR2 are used interchangeably. C R D It will be understood that the terms "heteroalkyl" and "heteroalkyl-" are not redundant or mutually exclusive. Rather, specific heteroalkyl groups are recited to add clarity. Thus, the term "heteroalkyl" refers to specific heteroalkyl groups, e.g., -CHO, -NR C R DNothing herein should be construed as excluding, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. Each example of a heteroalkyl group independently can be optionally substituted, i.e., it can be unsubstituted (an "unsubstituted heteroalkyl") or substituted with one or more substituents, e.g., 1 to 5 substituents, 1 to 3 substituents, or 1 substituent (a "substituted heteroalkyl").

[0032] 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 pi electrons shared by the cyclic array) having 6 to 14 ring carbon atoms and zero heteroatoms provided to the aromatic ring system ("C6-C 14 In some embodiments, an aryl group has 6 ring carbon atoms ("C aryl"; e.g., phenyl). In some embodiments, an aryl group has 10 ring carbon atoms ("C 10 Aryl"; e.g., naphthyl, such as 1-naphthyl and 2-naphthyl). In some embodiments, an aryl group has 14 ring carbon atoms ("C 14 aryl"; e.g., anthracyl). Aryl groups include, for example, C-C 10 In certain embodiments, an aryl group may be described as an unsubstituted C-C alkyl group, the term "membered" referring to a non-hydrogen ring atom within the moiety. Aryl groups include phenyl, naphthyl, indenyl, and tetrahydronaphthyl. Each instance of an aryl group may independently be optionally substituted, i.e., it may be unsubstituted (an "unsubstituted aryl") or substituted with one or more substituents (a "substituted aryl"). In certain embodiments, an aryl group is an unsubstituted C-C alkyl group. 14 In certain embodiments, the aryl group is a substituted C-C 14 It is aryl.

[0033] 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 by the cyclic array) having ring carbon atoms and 1 to 4 ring heteroatoms provided to the aromatic ring system ("5-10-membered heteroaryl"), where each heteroatom is independently selected from nitrogen, oxygen, and sulfur. In heteroaryl groups containing one or more nitrogen atoms, the point of attachment may be a carbon atom or a nitrogen atom, valence permitting. Heteroaryl bicyclic ring systems may contain one or more heteroatoms in one or both rings. "Heteroaryl" also includes ring systems in which a heteroaryl ring, as defined above, is fused to one or more aryl groups, with the point of attachment being on either the aryl or heteroaryl ring; in such cases, the number of ring members refers to the number of ring members in the fused (aryl / heteroaryl) ring system. In bicyclic heteroaryl groups in which one ring does not contain heteroatoms (e.g., indolyl, quinolinyl, carbazolyl, etc.), the point of attachment can be on either ring, i.e., on the ring with heteroatoms (e.g., 2-indolyl) or on the ring without heteroatoms (e.g., 5-indolyl). Heteroaryl groups can be described, for example, as 6- to 10-membered heteroaryl, where the term "member" refers to a non-hydrogen ring atom within the moiety. Each instance of heteroaryl can independently be optionally substituted, i.e., unsubstituted ("unsubstituted heteroaryl") or substituted with one or more substituents, e.g., 1-5 substituents, 1-3 substituents, or 1 substituent ("substituted heteroaryl").

[0034] Exemplary 5-membered heteroaryl groups containing one heteroatom include, but are not limited to, pyrrolyl, furanyl, and thiophenyl. Exemplary 5-membered heteroaryl groups containing two heteroatoms include, but are not limited to, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5-membered heteroaryl groups containing three heteroatoms include, but are not limited to, triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5-membered heteroaryl groups containing four heteroatoms include, but are not limited to, tetrazolyl. Exemplary 6-membered heteroaryl groups containing one heteroatom include, but are not limited to, pyridinyl. Exemplary 6-membered heteroaryl groups containing two heteroatoms include, but are not limited to, pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6-membered heteroaryl groups containing three or four heteroatoms include, but are not limited to, triazinyl and tetrazinyl, respectively. Exemplary 7-membered heteroaryl groups containing one heteroatom include, but are not limited to, azepinyl, oxepinyl, and thiepinyl. Exemplary 5,6-bicyclic heteroaryl groups include, but are not limited to, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzothiazolyl, benzisothiazolyl, benzothiadiazolyl, indolizinyl, and purinyl. Exemplary 6,6-bicyclic heteroaryl groups include, but are not limited to, naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl. Other exemplary heteroaryl groups include heme and heme derivatives.

[0035] As used herein, "cycloalkyl" refers to a radical of a non-aromatic cyclic hydrocarbon group having 3 to 10 ring carbon atoms and zero heteroatoms in the non-aromatic ring system ("C3-C 10 In some embodiments, a cycloalkyl group has 3 to 8 ring carbon atoms ("C3-C8 cycloalkyl"). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms ("C3-C6 cycloalkyl"). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms ("C3-C6 cycloalkyl"). In some embodiments, a cycloalkyl group has 5 to 10 ring carbon atoms ("C5-C 10 Cycloalkyl groups may be described, for example, as C4-C7 membered cycloalkyl, where the term "membered" refers to a non-hydrogen ring atom within the moiety. Exemplary C3-C6 cycloalkyl groups include, but are not limited to, cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), cyclohexadienyl (C6), and the like. Exemplary C3-C8 cycloalkyl groups include, but are not limited to, cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), cubanyl (C8), bicyclo[1.1.1]pentanyl (C5), bicyclo[2.2.2]octanyl (C8), bicyclo[2.1.1]hexanyl (C6), bicyclo[3.1.1]heptanyl (C7), and the like, in addition to the aforementioned C3-C6 cycloalkyl groups. 10 The cycloalkyl group includes, but is not limited to, the above-mentioned C3-C8 cycloalkyl groups, as well as cyclononyl (C9), cyclononenyl (C9), cyclodecyl (C 10 ), cyclodecenyl (C 10 ), octahydro-1H-indenyl (C9), decahydronaphthalenyl (C 10 ), spiro[4.5]decanyl (C 10), and the like. As the foregoing examples illustrate, in certain embodiments, cycloalkyl groups are monocyclic ("monocyclic cycloalkyl") or include fused, bridged, or spiro ring systems, such as bicyclic systems ("bicyclic cycloalkyl"), which can be saturated or partially unsaturated. "Cycloalkyl" also includes ring systems in which a cycloalkyl ring, as defined above, is fused to one or more aryl groups, and the point of attachment is on the cycloalkyl ring; in such cases, the number of carbon atoms continues to refer to the number of carbon atoms in the cycloalkyl ring system. Each instance of a cycloalkyl group can independently be optionally substituted, i.e., can be unsubstituted ("unsubstituted cycloalkyl") or substituted with one or more substituents ("substituted cycloalkyl"). In certain embodiments, a cycloalkyl group is an unsubstituted C3-C6 10 In certain embodiments, the cycloalkyl group is a substituted C-C 10 It is cycloalkyl.

[0036] As used herein, "heterocyclyl" refers to the radical of a 3- to 16-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon ("3- to 16-membered heterocyclyl"). In heterocyclyl groups containing one or more nitrogen atoms, the point of attachment can be a carbon atom or a nitrogen atom, where valence permits. Heterocyclyl groups can be either monocyclic ("monocyclic heterocyclyl") or fused, bridged, or spiro ring systems, such as bicyclic systems ("bicyclic heterocyclyl"), and can be saturated or partially unsaturated. Heterocyclyl bicyclic ring systems can contain one or more heteroatoms in one or both rings. "Heterocyclyl" also includes ring systems in which a heterocyclyl ring, as defined above, is fused to one or more cycloalkyl groups, with the point of attachment being on either the cycloalkyl or heterocyclyl ring, or in which a heterocyclyl ring, as defined above, is fused to one or more aryl or heteroaryl groups, with the point of attachment being on the heterocyclyl ring; in such cases, the number of ring members continues to refer to the number of ring members in the heterocyclyl ring system. A heterocyclyl group may be described, for example, as a 3- to 7-membered heterocyclyl, where the term "member" refers to the non-hydrogen ring atoms in the moiety, i.e., carbon, nitrogen, oxygen, sulfur, boron, phosphorus, and silicon. Each instance of heterocyclyl may independently be optionally substituted, i.e., unsubstituted ("unsubstituted heterocyclyl") or substituted with one or more substituents ("substituted heterocyclyl"). In certain embodiments, the heterocyclyl group is an unsubstituted 3- to 16-membered heterocyclyl. In certain embodiments, the heterocyclyl group is a substituted 3-16 membered heterocyclyl.

[0037] Exemplary 3-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azirtynyl, oxiranyl, and thiorenyl. Exemplary 4-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azetidinyl, oxetanyl, and thietanyl. Exemplary 5-membered heterocyclyl groups containing one heteroatom include, but are not limited to, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl, and pyrrolyl-2,5-dione. Exemplary 5-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, dioxolanyl, oxasulfuranyl, disulfuranyl, and oxazolidin-2-one. Exemplary 5-membered heterocyclyl groups containing three heteroatoms include, but are not limited to, triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6-membered heterocyclyl groups containing one heteroatom include, but are not limited to, piperidinyl (e.g., 2,2,6,6-tetramethylpiperidinyl), tetrahydropyranyl, dihydropyridinyl, pyridinonyl (e.g., 1-methylpyridin-2-onyl), and thianyl. Exemplary 6-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, piperazinyl, morpholinyl, pyridazinonyl (2-methylpyridazin-3-onyl), pyrimidinonyl (e.g., 1-methylpyrimidin-2-onyl, 3-methylpyrimidin-4-onyl), dithianyl, and dioxanyl. Exemplary 6-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, triazinanyl. Exemplary 7-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azepanyl, oxepanyl, and thiepanyl. Exemplary 8-membered heterocyclyl groups containing 1 heteroatom include, but are not limited to, azocanyl, oxecanyl, and thiocanyl.Exemplary 5-membered heterocyclyl groups (also referred to herein as 5,6-bicyclic heterocyclyl rings) fused to a C6 aryl ring include, but are not limited to, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, benzoxazolinonyl, and the like. Exemplary 5-membered heterocyclyl groups (also referred to herein as 5,5-bicyclic heterocyclyl rings) fused to a heterocyclyl ring include, but are not limited to, octahydropyrrolopyrrolyl (e.g., octahydropyrrolo[3,4-c]pyrrolyl), and the like. Exemplary 6-membered heterocyclyl groups (also referred to as 4,6-membered heterocyclyl rings) fused to a heterocyclyl ring include, but are not limited to, diazaspirononanyl (e.g., 2,7-diazaspiro[3.5]nonanyl). Exemplary 6-membered heterocyclyl groups fused to an aryl ring (also referred to herein as 6,6-bicyclic heterocyclyl rings) include, but are not limited to, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and the like. Exemplary 6-membered heterocyclyl groups fused to a cycloalkyl ring (also referred to herein as 6,7-bicyclic heterocyclyl rings) include, but are not limited to, 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 6,8-bicyclic heterocyclyl rings) include, but are not limited to, azabicyclononanyl (e.g., 9-azabicyclo[3.3.1]nonanyl).

[0038] The terms "alkylene," "alkenylene," "alkynylene," "haloalkylene," "heteroalkylene," "cycloalkylene," or "heterocyclylene," by themselves 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, for example, as C-C-membered alkylene, C-C-membered alkenylene, C-C-membered alkynylene, C-C-membered haloalkylene, C-C-membered heteroalkylene, C-C-membered cycloalkylene, or C-C-membered heterocyclylene, where the term "member" refers to a non-hydrogen ring atom within the moiety. For heteroalkylene and heterocyclylene groups, heteroatoms can also occupy either or both of the chain termini (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, etc.). Furthermore, the orientation of the linking group is not implied by the direction in which the formula of the linking group is written. For example, the formula -C(O)R'- can represent both -C(O)R'- and -R'C(O)-.

[0039] As used herein, the term "cyano" or "-CN" refers to a substituent having a carbon atom attached to a nitrogen atom by a triple bond, eg, C≡N.

[0040] As used herein, the term "halogen" or "halo" refers to fluorine, chlorine, bromine or iodine.

[0041] As used herein, the term "hydroxy" refers to --OH.

[0042] As used herein, the term "nitro" refers to a substituent having two oxygen atoms bonded to a nitrogen atom, eg, --NO.sub.2.

[0043] As used herein, the term "nucleobase" refers to the basic building blocks of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), which are nitrogen-containing biological compounds found linked to sugars in nucleosides. The major nucleobases, 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 occur in DNA, these molecules are called DNA bases, and A, G, C, and U are called RNA bases. Adenine and guanine belong to a class of double-ring molecules called purines (abbreviated as R). Cytosine, thymine, and uracil are all pyrimidines. Other nucleobases that do not function as a normal part of the genetic code are referred to as non-naturally occurring. In one embodiment, the nucleobases can be chemically modified, for example, with alkyl (eg, methyl), halo, -O-alkyl, or other modifications.

[0044] As used herein, the term "nucleic acid" refers to deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) and polymers thereof in either single- or double-stranded form. The term "nucleic acid" includes genes, cDNAs, pre-mRNAs, or mRNAs. In one embodiment, nucleic acid molecules are synthetic (e.g., chemically synthesized) or recombinant. Unless otherwise specified, the term encompasses nucleic acids containing analogs or derivatives of natural nucleotides that have similar binding properties as the reference nucleic acid and are metabolized similarly to natural nucleotides. Unless otherwise specified, a particular nucleic acid sequence implicitly encompasses not only the sequence explicitly indicated, but also its conservatively modified variants (e.g., degenerate codon substitutions), alleles, orthologs, SNPs, and complementary sequences.

[0045] As used herein, "oxo" refers to carbonyl, i.e., --C(O)--.

[0046] As used herein with respect to compounds of formula (I), the symbol " [ka] " refers to a point of attachment to another moiety or functional group within a compound.

[0047] Alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups defined herein are optionally substituted. In general, the term "substituted," whether preceded by the term "optionally" or not, means that at least one hydrogen atom present on the group (e.g., a carbon or nitrogen atom) is replaced with a permissible substituent, e.g., a substituent that, when substituted, results in a stable compound, e.g., a compound that does not spontaneously undergo transformation, such as by rearrangement, cyclization, elimination, or other reaction. Unless otherwise specified, 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 substituents can be the same or different at each position. The term "substituted" is intended to include substitution with all permissible substituents of organic compounds, including any of the substituents described herein, that result in the formation of stable compounds. The present disclosure contemplates any and all such combinations in order to arrive at stable compounds. For purposes of this invention, the heteroatoms such as nitrogen may have hydrogen substituents and / or any suitable substituents described herein that satisfy the valence of the heteroatom and result in the formation of a stable moiety.

[0048] Two or more substituents may optionally be bonded to form an aryl, heteroaryl, cycloalkyl, or heterocyclyl group. Such so-called ring-forming substituents are typically, but not necessarily, found attached to a cyclic base structure. In one embodiment, the ring-forming substituents are bonded to adjacent members of the base structure. For example, two ring-forming substituents attached to adjacent members of a cyclic base structure form a fused ring structure. In another embodiment, the ring-forming substituents are bonded to one member of the base structure. For example, two ring-forming substituents attached to one member of a cyclic base structure form a spiro ring structure. In yet another embodiment, the ring-forming substituents are bonded to non-adjacent members of the base structure.

[0049] The compounds provided herein may exist in one or more specific geometric isomers, optical isomers, enantiomers, diastereomers, epimers, stereoisomers, tautomers, conformers, 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").

[0050] The compounds described herein may contain one or more asymmetric centers and therefore may exist in various isomeric forms, e.g., enantiomers and / or diastereomers. For example, the compounds described herein may be in the form of individual enantiomers, diastereomers, or geometric isomers, or may be in the form of mixtures of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomers. In one 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-performance liquid chromatography (HPLC) and the formation and crystallization of chiral salts, or preferred isomers can be prepared by asymmetric synthesis. 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 (EL Eliel, Ed., University of Notre Dame Press, Notre Dame, IN 1972). The present disclosure further encompasses the compounds described herein as individual isomers substantially free of other isomers or as mixtures of various isomers.

[0051] As used herein, a pure enantiomer compound is substantially free of other enantiomers or stereoisomers of the compound (i.e., in enantiomeric excess). In other words, the "S" form of a compound is substantially free of the "R" form of the compound and is therefore in enantiomeric excess over the "R" form. The terms "enantiomerically pure" or "pure enantiomer" refer to a compound that contains more than 75%, more than 80%, more than 85%, more than 90%, more than 91%, more than 92%, more than 93%, more than 94%, more than 95%, more than 96%, more than 97%, more than 98%, more than 99%, more than 99.5%, or more than 99.9% by weight of an enantiomer. In certain embodiments, the weight is based on the total weight of all enantiomers or stereoisomers of the compound.

[0052] In the compositions provided herein, the enantiomerically pure compound may be present together with other active or inactive ingredients. For example, a pharmaceutical composition containing an enantiomerically pure R compound may contain, for example, about 90% excipients and about 10% enantiomerically pure R compound. In certain embodiments, the enantiomerically pure R compound in such a composition may contain, for example, at least about 95% by weight of the R compound and up to about 5% by weight of the S compound, based on the total weight of the compound. For example, a pharmaceutical composition containing an enantiomerically pure S compound may contain, for example, about 90% excipients and about 10% of the enantiomerically pure S compound. In certain embodiments, the enantiomerically pure S compound in such a composition may contain, for example, at least about 95% by weight of the S compound and up to about 5% by weight of the R compound, based on the total weight of the compound.

[0053] In some embodiments, diastereomerically pure compounds may be present together with other active or inactive ingredients. For example, a pharmaceutical composition comprising a diastereomerically pure exo compound may contain, for example, about 90% excipients and about 10% diastereomerically pure exo compound. In certain embodiments, the diastereomerically pure exo compound in such a composition may contain, for example, at least about 95% by weight of the exo compound and up to about 5% by weight of the endo compound, based on the total weight of the compound. For example, a pharmaceutical composition comprising a diastereomerically pure endo compound may contain, for example, about 90% excipients and about 10% of the diastereomerically pure endo compound. In certain embodiments, the diastereomerically pure endo compound in such a composition may contain, for example, at least about 95% by weight of the endo compound and up to about 5% by weight of the exo compound, based on the total weight of the compound.

[0054] In some embodiments, isomerically pure compounds may be present together with other active or inactive ingredients. For example, a pharmaceutical composition comprising an isomerically pure exo compound may contain, for example, about 90% excipients and about 10% isomerically pure exo compound. In certain embodiments, the isomerically pure exo compound in such a composition may contain, for example, at least about 95% by weight of the exo compound and up to about 5% by weight of the endo compound, based on the total weight of the compound. For example, a pharmaceutical composition comprising an isomerically pure endo compound may contain, for example, about 90% excipients and about 10% of the isomerically pure endo compound. In certain embodiments, the isomerically pure endo compound in such a composition may contain, for example, at least about 95% by weight of the endo compound and up to about 5% by weight of the exo compound, based on the total weight of the compound.

[0055] In certain embodiments, the active ingredient can be formulated with few or no excipients or carriers.

[0056] The compounds described herein may contain one or more isotopic substitutions. For example, H is1 H, 2 H (D or deuterium), and 3 H (T or tritium), and C can be in any isotopic form. 12 C. 13 C, and 14 C can be any isotopic form, including O 16 O and 18 It can be any isotopic form including O, and N is 14 N and 15 N may be any isotopic form, including F. 18 F, 19 It can be any isotopic form containing F.

[0057] The term "pharmaceutically acceptable salt" is intended to include salts of active compounds prepared using relatively non-toxic acids or bases, depending on the specific substituents found on the compounds described herein.When a compound of the present disclosure contains a relatively acidic functional group, a base addition salt can be obtained by contacting the neutral form of such a compound with a sufficient amount of the desired base, either directly or in a suitable inert solvent.Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salts, or similar salts.When a compound of the present disclosure contains a relatively basic functional group, a neutral form of such a compound can be contacted with a sufficient amount of the desired acid, either directly or in a suitable inert solvent, to obtain an acid addition salt. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, monohydrogencarbonic acid, phosphoric acid, monohydrogenphosphate, dihydrogenphosphate, sulfuric acid, monohydrogensulfuric acid, hydroiodic acid, or phosphorous acid, as well as salts derived from organic acids such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-tolylsulfonic acid, citric acid, tartaric acid, and methanesulfonic acid. Also included are salts of amino acids such as alginate, and salts of organic acids such as glucuronic acid or galactunolonic acid (see, for example, Berge et al., Journal of Pharmaceutical Science 66:1-19 (1977)). Certain specific compounds of the present invention contain both basic and acidic functional groups, allowing the compounds to be converted into either base or acid addition salts. These salts can be prepared by methods known to those skilled in the art. Other pharmaceutically acceptable carriers known to those skilled in the art are suitable for the present invention.

[0058] In addition to salt forms, the present disclosure provides compounds in prodrug form. Prodrugs of the compounds described herein are compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the present invention. Furthermore, 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.

[0059] The term "solvate" refers to a form of a compound associated with a solvent, usually via a solvolysis reaction. This physical association may involve hydrogen bonding. Conventional solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, and the like. A compound of formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX) may be prepared, for example, in crystalline form and may be solvated. Suitable solvates include pharmaceutically acceptable solvates, further including both stoichiometric and non-stoichiometric solvates. In certain cases, a solvate may be isolated, for example, when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid. "Solvate" encompasses both solution-phase and isolatable solvates. Representative solvates include hydrates, ethanolates, and methanolates.

[0060] The term "hydrate" refers to a compound associated with water. Typically, the number of water molecules contained in a hydrate of a compound is a fixed ratio to the number of compound molecules in the hydrate. Thus, a hydrate of a compound can be represented, for example, by the general formula R-xH2O, where R is the compound and x is a number greater than 0. A given compound can form multiple types of hydrates, including, for example, a monohydrate (x is 1), a lower hydrate (x is a number greater than 0 and less than 1, e.g., a hemihydrate (R-0.5H2O)), and a polyhydrate (x is a number greater than 1, e.g., a dihydrate (R-2H2O) and a hexahydrate (R-6H2O)).

[0061] The term "tautomer" refers to interchangeable forms of a particular compound structure that differ in the substitution of hydrogen atoms and electrons. Thus, two structures can be in equilibrium due to the shift of π electrons and atoms (usually H). For example, enols and ketones are tautomers because they are rapidly interconverted by treatment with either acid or base. Another example of a tautomer is the aci- and nitro-forms of phenylnitromethane, which are similarly formed by treatment with acid or base. Tautomeric forms can be relevant to achieving optimal chemical reactivity and biological activity of a compound of interest.

[0062] Other definitions The following definitions are of more general terms used throughout this disclosure.

[0063] The articles "a" and "an" refer to one or to more than one (e.g., 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 otherwise specified.

[0064] The term "about" is used herein to mean within a typical acceptable range 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 ranges, it is understood that "about" can modify each of the numbers in the series or range.

[0065] As used herein, "obtain" or "obtaining" refers to obtaining a value, e.g., a numerical value, or an image, or a physical entity (e.g., a sample), by "directly obtaining" or "indirectly obtaining" the value or physical entity. "Directly obtaining" means performing a process (e.g., running an analytical method or protocol) to obtain the value or physical entity. "Indirectly obtaining" refers to receiving a value or physical entity from another party or source (e.g., a third-party laboratory that directly obtained the physical entity or value). Directly obtaining a value or physical entity includes performing a process that involves a physical change of a physical substance or the use of a machine or device. An example of directly obtaining a value is obtaining a sample from a human subject. Directly obtaining a value includes performing a process that uses a machine or device, e.g., a mass spectrometer, to obtain mass spectrometry data.

[0066] The terms "administer," "administering," or "administration," as used herein, refer to implantation, absorption, ingestion, injection, inhalation, or otherwise introduction of the pharmaceutical composition.

[0067] As used herein, the terms "condition," "disease," and "disorder" are used interchangeably.

[0068] An "effective amount" of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX) refers to an amount sufficient to elicit a desired biological response, i.e., treat a condition. As will be understood by those skilled in the art, the effective amount of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX) can vary depending on factors such 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 both therapeutic and prophylactic treatments. For example, in the treatment of cancer, an effective amount of a compound of the present invention can reduce tumor burden or halt tumor growth or spread.

[0069] A "therapeutically effective amount" of a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX) 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 refers to an amount of a therapeutic agent that, alone or in combination with other therapies, provides a therapeutic benefit in the treatment of a condition. The term "therapeutically effective amount" can encompass an amount that improves overall therapy, reduces or avoids the symptoms or causes of a condition, or enhances the therapeutic effect of another therapeutic agent.

[0070] The terms "peptide," "polypeptide," and "protein" are used interchangeably and refer to compounds composed of amino acid residues covalently linked by peptide bonds. A protein or peptide must contain at least two amino acids, and there is no limit to the maximum number of amino acids it may contain. A polypeptide includes any peptide or protein containing two or more amino acids joined to each other by peptide bonds. As used herein, the term refers to both short chains, e.g., also commonly referred to in the art as peptides, oligopeptides, and oligomers, and to the many types of longer chains commonly referred to in the art as proteins.

[0071] As used herein, "prevention," "prevent," and "preventing" refer to treatment that involves administering a therapy, e.g., administering a compound described herein (e.g., a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX)), prior to the onset of a disease, disorder, or condition to prevent the physical manifestation of the 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 occurred or been observed. In some embodiments, treatment includes prevention, while in other embodiments, it does not include prevention.

[0072] "Subjects" to which administration is intended include, but are not limited to, humans (i.e., male or female of any age, e.g., a pediatric subject (e.g., infant, child, adolescent) or an adult subject (e.g., a young adult, middle-aged adult, or elderly adult)) and / or other non-human animals, such as mammals (e.g., primates (e.g., cynomolgus monkeys, rhesus monkeys); commercially relevant mammals such as cows, 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 male or female and at any stage of development. The non-human animal may be a transgenic animal.

[0073] As used herein, the terms "treatment," "treat," and "treating" refer to the amelioration, alleviation, delay in onset, or inhibition of progression of one or more symptoms, manifestations, or underlying causes of a disease, disorder, or condition (e.g., those described herein), e.g., by performing a therapy, e.g., by administering a compound described herein (e.g., a compound of Formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), or (IX)). In one embodiment, treating includes a reduction, amelioration, alleviation, delay in onset, or inhibition of progression of a symptom of a disease, disorder, or condition. In one embodiment, treating includes a reduction, amelioration, alleviation, delay in onset, or inhibition of progression of a disease, disorder, or condition. In one embodiment, treating includes a reduction, amelioration, alleviation, reduction, or delay in onset of an underlying cause of a disease, disorder, or condition. In some embodiments, "treatment," "treat," and "treating" require that a sign or symptom of a disease, disorder, or condition has occurred or has been observed. In other embodiments, treatment may be administered when there are no signs or symptoms of the disease or condition, e.g., in prophylactic 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 disappeared, e.g., to delay or prevent recurrence. Treatment may also be continued after symptoms have disappeared, e.g., to delay or prevent recurrence. In some embodiments, treatment includes prevention, and in other embodiments, it does not include prevention.

[0074] "Proliferative disease" refers to a disease caused by the abnormal expansion of cells through proliferation (Walker, Cambridge Dictionary of Biology; Cambridge University Press: Cambridge, UK, 1990). Proliferative diseases can be associated with: 1) pathological proliferation of normal, quiescent cells; 2) pathological migration of cells from their normal location (e.g., metastasis of neoplastic cells); 3) pathological expression of proteolytic enzymes such as matrix metalloproteinases (e.g., collagenase, gelatinase, and elastase); 4) pathological angiogenesis, such as proliferative retinopathy and tumor metastasis; or 5) evasion of host immune surveillance and elimination of neoplastic cells. Exemplary proliferative diseases include cancer (i.e., "malignant neoplasms"), benign neoplasms, and angiogenesis.

[0075] "Non-proliferative disease" refers to a disease that does not spread primarily through abnormal cell proliferation. Non-proliferative diseases can be associated with any cell or tissue type in a subject. Exemplary non-proliferative diseases include nervous system diseases or disorders (e.g., repeat expansion diseases); autoimmune diseases 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; kidney diseases or disorders; and infectious diseases.

[0076] compound In one aspect, the present disclosure provides a compound of formula (I): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A is cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 optionally replaced by R B is B, C1-C6-alkyl, or C1-C6-heteroalkyl, where alkyl and heteroalkyl are selected from the group consisting of one or more R 10and B is cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is substituted with one or more R 1 optionally substituted with one or more R 1 and optionally replaced by L 1 and L 2 each independently represents absence, C-C-alkylene, C-C-heteroalkylene, —O—, —C(O)—, —N(R 4 )-, -N(R 4 )C(O)-, or -C(O)N(R 4 )-, where each alkylene and heteroalkylene is selected from one or more R 9 and Y is optionally substituted with N, C(R 6a ), or C(R 6a )(R 6b ), where the dashed line in the ring containing Y can be a single or double bond, valence permitting, and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -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 selected from the group consisting of one or more R 5 or two R 1The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 and each R 2 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -C(O)NR B R C , -NR B C(O)R D , or -S(O) x R D and R 3 is C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , C(O)NR B R C , -NR B C(O)R D , or -S(O) x R D and R 4 is hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D, -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 optionally replaced by R 6a and R 6b are independently hydrogen, C-C-alkyl, C-C-heteroalkyl, C-C-haloalkyl, or halo, and each R 7 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 9 and each R B and R C are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -OR A , -S(O) x R D or R B and R Ctogether with the atoms to which they are attached form one or more R 9 and each R D are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 9 and R 10 are independently C1-C6-alkyl, halo, or -OR A1 wherein n is 0, 1, or 2; m is 0, 1, 2, or 3; and x is 0, 1, or 2.

[0077] In another aspect, the present disclosure provides a compound of formula (II): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 and optionally replaced by L 1 and L 2 each independently represents absence, C-C-alkylene, C-C-heteroalkylene, —O—, —C(O)—, —N(R 8 )-, -N(R 8 )C(O)-, or -C(O)N(R 8 )-, where each alkylene and heteroalkylene is selected from one or more R 9 and each of W, X, and Z is independently C(R 3 ) or N, and Y is N, N(R 4a ), C(R 4b ), or C(R 4b )(R 4c ), where the dashed line in the ring containing Y can be a single or double bond, valence permitting, and each R1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -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 selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 optionally replaced by R 2 is absent, hydrogen, or C1-C6-alkyl, and R 3 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , -C(O)R D , or -S(O) x R D and R 4a is hydrogen, C-C-alkyl, C-C-heteroalkyl, or C-C-haloalkyl, and R 4b and R 4ceach independently represents hydrogen, C-C-alkyl, C-C-heteroalkyl, C-C-haloalkyl, halo, or -OR A and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 and each R 6 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R 8 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 9 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, halo, cyano, oxo, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and each R A are independently hydrogen, C-C alkyl, C-C haloalkyl, aryl, heteroaryl, C-C alkylene-aryl, C-C alkylene-heteroaryl, -C(O)R D , or -S(O) x RD and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, -OR A or R B and R C together with the atoms to which they are attached form one or more R 10 and each R D are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 10 is independently C1-C6-alkyl or halo, and x is 0, 1, or 2.

[0078] In another aspect, the present disclosure provides a compound of formula (III): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 and optionally replaced by L 1 and L 2 each independently represents absence, C-C-alkylene, C-C-heteroalkylene, —O—, —C(O)—, —N(R 8 )-, -N(R 8 )C(O)-, or -C(O)N(R 8 )-, where each alkylene and heteroalkylene is selected from one or more R 9 and each of X and Z is independently C(R 3 ) or N, and Y is N, C, or C(R 4b), where the dashed line in the ring containing Y can be a single or double bond, valence permitting, and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -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 selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 optionally replaced by R 2 is absent, hydrogen, or C1-C6-alkyl, and R 3 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , -C(O)R D , or -S(O) x R D and R 4bis hydrogen, C-C-alkyl, C-C-heteroalkyl, or C-C-haloalkyl, and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 and each R 6 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and R 7a is hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, oxo, or -OR A and R 7b is hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and each R 8 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 9 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, halo, cyano, oxo, -OR A , -NR B R C , -C(O)R D , or -C(O)OR Dand each R A are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 9 and each R B and R C are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -OR A , -S(O) x R D or R B and R C together with the atoms to which they are attached form one or more R 9 and each R D are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 10 is independently C1-C6-alkyl or halo, and x is 0, 1, or 2.

[0079] In another aspect, the present disclosure provides a compound of formula (IV): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 and W and X are independently C(R 3 ) or N, and L 1 and L 2 each independently represents absence, C-C-alkylene, C-C-heteroalkylene, —O—, —C(O)—, —N(R 4 )-, -N(R 4 )C(O)-, or -C(O)N(R 4 )-, where each alkylene and heteroalkylene is selected from one or more R 6 and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C2-C6 alkenylene-aryl, heteroaryl, C1-C6 alkylene-heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -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 selected from the group consisting of one or more R 5 or two R 1The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 optionally replaced by R 2a , R 2b , and R 2c are each independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -C(O)NR B R C , or -S(O) x R D and R 3 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -C(O)NR B R C , or -S(O) x R D and R 4 is hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B RC , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 6 and R 7 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, cycloalkyl, heterocyclyl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, cycloalkyl, heterocyclyl, -OR A , -S(O) x R D or R B and R C together with the atoms to which they are attached form one or more R 9 and each R D are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 9is independently C1-C6-alkyl or halo, and X is 0, 1, or 2.

[0080] In another aspect, the present disclosure provides a compound of formula (V): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 and W, X, and Y are each independently C(R 3 ) or N, wherein at least one of W, X, and Y is independently N; and L 1 and L 2 each independently represents absence, C-C-alkylene, C-C-heteroalkylene, —O—, —C(O)—, —N(R 4 )-, -N(R 4 )C(O)-, or -C(O)N(R 4 )-, where each alkylene and heteroalkylene is selected from one or more R 6 and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C2-C6 alkenylene-aryl, heteroaryl, C1-C6 alkylene-heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R Dwherein each alkyl, alkylene, alkenyl, alkenylene, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 optionally replaced by R 2 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -C(O)NR B R C , or -S(O) x R D and R 3 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -C(O)NR B R C , or -S(O) x R D and R 4 is hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NRB R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 6 and R 7 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, cycloalkyl, heterocyclyl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, cycloalkyl, heterocyclyl, -OR A , -S(O) x R D or R B and R C together with the atoms to which they are attached form one or more R 9 and each R Dare independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 9 is independently C1-C6-alkyl or halo, and x is 0, 1, or 2.

[0081] In another aspect, the present disclosure provides a compound of formula (VI): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 and W and X are independently C(R 3 ) or N, and L 1 and L 2 each independently represents absence, C-C-alkylene, C-C-heteroalkylene, —O—, —C(O)—, —N(R 4 )-, -N(R 4 )C(O)-, or -C(O)N(R 4 )-, where each alkylene and heteroalkylene is selected from one or more R 6 and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C2-C6 alkenylene-aryl, heteroaryl, C1-C6 alkylene-heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B RC , -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 selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 optionally replaced by R 2a , R 2b , and R 2c are each independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -C(O)NR B R C , or -S(O) x R D and R 3 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -C(O)NR B R C , or -S(O) x R D and R 4 is hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 6 and R 7 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, cycloalkyl, heterocyclyl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, cycloalkyl, heterocyclyl, -OR A , -S(O) x R D or R B and R C together with the atoms to which they are attached form one or more R 9and each R D are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 9 is independently C1-C6-alkyl or halo, and x is 0, 1, or 2.

[0082] In another aspect, the present disclosure provides a compound of formula (VII): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 and optionally replaced by L 1 and L 2 each independently represents absence, C-C-alkylene, C-C-heteroalkylene, —O—, —C(O)—, —N(R 4 )-, -N(R 4 )C(O)-, or -C(O)N(R 4 )-, where each alkylene and heteroalkylene is selected from one or more R 6 and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C2-C6 alkenylene-aryl, heteroaryl, C1-C6 alkylene-heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NRB 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 selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 optionally replaced by R 2a , R 2b , and R 2c are each independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -C(O)NR B R C , or -S(O) x R D and R 4 is hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D, -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 6 and R 7 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, cycloalkyl, heterocyclyl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, cycloalkyl, heterocyclyl, -OR A , -S(O) x R D or R B and R C together with the atoms to which they are attached form one or more R 9 and each R D are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 9 is independently C1-C6-alkyl or halo, and x is 0, 1, or 2.

[0083] In another aspect, the present invention provides a compound of formula (VIII): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 and optionally replaced by L 1 and L 2 each independently represents absence, C-C-alkylene, C-C-heteroalkylene, —O—, —C(O)—, —N(R 8 )-, -N(R 8 )C(O)-, or -C(O)N(R 8 )-, where each alkylene and heteroalkylene is selected from one or more R 9 and each of W, X, and Z is independently C(R 3 ) or N, and Y is N, C, or C(R 4b ), where the dashed line in the ring containing Y can be a single or double bond, valence permitting, and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C2-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R Dwherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 optionally replaced by R 2 is absent, hydrogen, or C1-C6-alkyl, and R 3 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and R 4b is hydrogen, C-C-alkyl, C-C-heteroalkyl, or C-C-haloalkyl, and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 and each R 6are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and R 7 is hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, oxo, or -OR A and each R 8 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 9 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, halo, cyano, oxo, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and each R A are independently hydrogen, C-C alkyl, C-C haloalkyl, aryl, heteroaryl, C-C alkylene-aryl, C-C alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, -OR A or R B and R C together with the atoms to which they are attached form one or more R 10 and each R D are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 10 is independently C1-C6-alkyl or halo, and x is 0, 1, or 2.

[0084] In another aspect, the present disclosure provides a compound of formula (IX): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 and optionally replaced by L 1 and L 2 Each of the groups is selected from the group consisting of absence, C-C-alkylene, C-C-heteroalkylene, —O—, —C(O)—, —N(R 8 )-, -N(R 8 )C(O)-, or -C(O)N(R 8 )-, where each alkylene and heteroalkylene is selected from one or more R 9 and each of X and Z is independently C(R 3 ) or N, and Y is N, N(R 4a ), C(R 4b ), or C(R 4b )(R 4c ), where the dashed line in the ring containing Y can be a single or double bond, valence permitting, and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C2-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x RD wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 optionally replaced by R 2 is absent, hydrogen, or C1-C6-alkyl, and R 3 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and R 4a is hydrogen, C-C-alkyl, C-C-heteroalkyl, or C-C-haloalkyl, and R 4b and R 4c each independently represents hydrogen, C-C-alkyl, C-C-heteroalkyl, C-C-haloalkyl, halo, or -OR A and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R Dwherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 and each R 6 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and R 7b is hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and each R 8 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 9 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, halo, cyano, oxo, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and each R A are independently hydrogen, C-C alkyl, C-C haloalkyl, aryl, heteroaryl, C-C alkylene-aryl, C-C alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, -OR A or R B and R C together with the atoms to which they are attached form one or more R 10 and each R Dare independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 10 is independently C1-C6-alkyl or halo, and x is 0, 1, or 2.

[0085] As outlined herein for compounds of formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), and (IX), each of A or B is independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which may be selected from one or more R 1 is optionally replaced by

[0086] In some embodiments, each of A and B is independently a monocyclic ring, e.g., a monocyclic cycloalkyl, a monocyclic heterocyclyl, a monocyclic aryl, or a monocyclic heteroaryl. The monocyclic ring can be saturated, partially unsaturated, or fully unsaturated (e.g., aromatic). In some embodiments, A or B is independently a monocyclic ring containing 3 to 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 independently selects one or more R 1 is a monocyclic ring optionally substituted with

[0087] In some embodiments, A or B is independently a bicyclic ring, e.g., a bicyclic cycloalkyl, a bicyclic heterocyclyl, a bicyclic aryl, or a bicyclic heteroaryl. The bicyclic ring can be saturated, partially unsaturated, or fully unsaturated (e.g., aromatic). In some embodiments, A or B is independently a bicyclic ring comprising a fused, bridged, or spiro ring system. In some embodiments, A or B is independently a bicyclic ring comprising 4 to 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 independently selects one or more R 1 is a bicyclic ring optionally substituted with

[0088] In some embodiments, A or B is independently a tricyclic ring, e.g., a tricyclic cycloalkyl, a tricyclic heterocyclyl, a tricyclic aryl, or a tricyclic heteroaryl. The tricyclic ring can be saturated, partially unsaturated, or fully unsaturated (e.g., aromatic). In some embodiments, A or B is independently a tricyclic ring containing a fused, bridged, or spiro ring system, or a combination thereof. In some embodiments, A or B is independently a tricyclic ring containing 6 to 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 independently selects one or more R 1 is a tricyclic ring optionally substituted with

[0089] In some embodiments, A or B is independently a monocyclic cycloalkyl, a monocyclic heterocyclyl, a monocyclic aryl, or a monocyclic heteroaryl. In some embodiments, A or B is independently a bicyclic cycloalkyl, a bicyclic heterocyclyl, a bicyclic aryl, or a bicyclic heteroaryl. In some embodiments, A or B is independently a tricyclic cycloalkyl, a tricyclic heterocyclyl, a tricyclic aryl, or a tricyclic heteroaryl. In some embodiments, A is a monocyclic heterocyclyl. In some embodiments, B is a monocyclic heterocyclyl. In some embodiments, A is a bicyclic heterocyclyl. In some embodiments, B is a bicyclic heterocyclyl. In some embodiments, A is a monocyclic heteroaryl. In some embodiments, B is a monocyclic heteroaryl. In some embodiments, A is a bicyclic heteroaryl. In some embodiments, B is a bicyclic heteroaryl.

[0090] In some embodiments, A or B is independently a nitrogen-containing heterocyclyl, for example, a heterocyclyl containing one or more nitrogen atoms. The one or more nitrogen atoms of the nitrogen-containing heterocyclyl can be located at any position on the ring. In some embodiments, the nitrogen-containing heterocyclyl is monocyclic, bicyclic, or tricyclic. In some embodiments, A or B is independently a heterocyclyl containing 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 a heterocyclyl containing one nitrogen atom. In some embodiments, B is a heterocyclyl containing one nitrogen atom. In some embodiments, A is a heterocyclyl containing two nitrogen atoms. In some embodiments, B is a heterocyclyl containing two nitrogen atoms. In some embodiments, A is a heterocyclyl containing three nitrogen atoms. In some embodiments, B is a heterocyclyl containing three nitrogen atoms. In some embodiments, A is a heterocyclyl containing four nitrogen atoms. In some embodiments, B is a heterocyclyl containing four nitrogen atoms. In some embodiments, A or B is independently a nitrogen-containing heterocyclyl containing one or more additional heteroatoms, such as one or more of oxygen, sulfur, boron, silicon, or phosphorus. In some embodiments, one or more nitrogens of the nitrogen-containing heterocyclyl can be, for example, R 1 is replaced by

[0091] In some embodiments, A or B is independently a nitrogen-containing heteroaryl, e.g., a heteroaryl containing one or more nitrogen atoms. The one or more nitrogen atoms of the nitrogen-containing heteroaryl can be present at any position in the ring. In some embodiments, the nitrogen-containing heteroaryl is monocyclic, bicyclic, or tricyclic. In some embodiments, A or B is independently a heteroaryl containing 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 a heteroaryl containing one nitrogen atom. In some embodiments, B is a heteroaryl containing one nitrogen atom. In some embodiments, A is a heteroaryl containing two nitrogen atoms. In some embodiments, B is a heteroaryl containing two nitrogen atoms. In some embodiments, A is a heteroaryl containing three nitrogen atoms. In some embodiments, B is a heteroaryl containing three nitrogen atoms. In some embodiments, A is a heteroaryl containing four nitrogen atoms. In some embodiments, B is a heteroaryl containing four nitrogen atoms. In some embodiments, A or B is independently a nitrogen-containing heteroaryl containing one or more additional heteroatoms, such as one or more of oxygen, sulfur, boron, silicon, or phosphorus. In some embodiments, one or more nitrogens in the nitrogen-containing heteroaryl can be, for example, R 1 is replaced by

[0092] In some embodiments, A is a nitrogen-containing 6-membered heterocyclyl, for example, a 6-membered heterocyclyl containing one or more nitrogen atoms. In some embodiments, A is a 6-membered heterocyclyl containing one nitrogen atom. In some embodiments, A is a 6-membered heterocyclyl containing two nitrogen atoms. In some embodiments, A is a 6-membered heterocyclyl containing three nitrogen atoms. In some embodiments, A is a 6-membered heterocyclyl containing four nitrogen atoms. The one or more nitrogen atoms of the nitrogen-containing 6-membered heterocyclyl can be located at any position on the ring. In some embodiments, A is a 6-membered heterocyclyl containing one or more R 1 In some embodiments, one or more nitrogens of the nitrogen-containing 6-membered heterocyclyl may be optionally substituted with, for example, R 1 In some embodiments, A is a nitrogen-containing 6-membered heterocyclyl containing one or more additional heteroatoms, such as one or more of oxygen, sulfur, boron, silicon, or phosphorus.

[0093] In some embodiments, B is a nitrogen-containing 5-membered heterocyclyl or heteroaryl, for example, a 5-membered heterocyclyl or heteroaryl containing one or more nitrogen atoms. In some embodiments, B is a 5-membered heterocyclyl containing one nitrogen atom. In some embodiments, B is a 5-membered heteroaryl containing one nitrogen atom. In some embodiments, B is a 5-membered heterocyclyl containing two nitrogen atoms. In some embodiments, B is a 5-membered heteroaryl containing two nitrogen atoms. In some embodiments, B is a 5-membered heterocyclyl containing three nitrogen atoms. In some embodiments, B is a 5-membered heteroaryl containing three nitrogen atoms. The one or more nitrogen atoms of the nitrogen-containing 5-membered heterocyclyl or heteroaryl can be located at any position on the ring. In some embodiments, B is selected from the group consisting of one or more R 1 In some embodiments, B is a nitrogen-containing 5-membered heterocyclyl optionally substituted with one or more R 1In some embodiments, one or more nitrogens of the nitrogen-containing 5-membered heterocyclyl or heteroaryl may be optionally substituted with, for example, R 1 In some embodiments, B is a nitrogen-containing 5-membered heterocyclyl or heteroaryl containing one or more additional heteroatoms, such as one or more of oxygen, sulfur, boron, silicon, or phosphorus.

[0094] In some embodiments, B is one or more R 1 In some embodiments, B is a 9-membered bicyclic heteroaryl containing one nitrogen atom. In some embodiments, B is a 9-membered bicyclic heteroaryl containing two nitrogen atoms. In some embodiments, B is a 9-membered bicyclic heteroaryl containing three nitrogen atoms. In some embodiments, B is a 9-membered bicyclic heteroaryl containing four nitrogen atoms. The one or more nitrogen atoms of the 9-membered bicyclic heteroaryl can be located at any position on the ring. In some embodiments, B is a 9-membered bicyclic heteroaryl containing one or more R 1 is a 9-membered bicyclic heteroaryl substituted with

[0095] In some embodiments, each of A and B is [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] wherein each R 1 is as defined herein. In one embodiment, A and B are each independently a saturated, partially saturated, or unsaturated (e.g., aromatic) derivative of one of the above rings. In one embodiment, A and B are each independently a stereoisomer of one of the above rings.

[0096] In some embodiments, each of A and B is [ka] [ka] are independently selected from 1 is as defined herein. In one embodiment, A and B are each independently a saturated, partially saturated, or unsaturated (e.g., aromatic) derivative of one of the above rings. In one embodiment, A and B are each independently a stereoisomer of one of the above rings.

[0097] In some embodiments, A is heterocyclyl. In some embodiments, A is nitrogen-containing heterocyclyl. In some embodiments, A is monocyclic nitrogen-containing heterocyclyl. In some embodiments, A is [ka] is selected from.

[0098] In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0099] In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0100] In some embodiments, A is [ka] is selected from.

[0101] In some embodiments, A is heteroaryl. In some embodiments, A is a nitrogen-containing heteroaryl. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl. In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0102] In some embodiments, A is [ka] In some embodiments, A is selected from: [ka] where R 1 is as defined herein. In some embodiments, A is [ka] is selected from.

[0103] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] is.

[0104] In some embodiments, B is heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] In some embodiments, B is selected from: [ka] where R 1 is as defined herein.

[0105] In some embodiments, B is [ka] is selected from.

[0106] In some embodiments, B is heterocyclyl. In some embodiments, B is nitrogen-containing heterocyclyl. In some embodiments, B is a monocyclic nitrogen-containing heterocyclyl or a bicyclic nitrogen-containing heterocyclyl.

[0107] In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1is as defined herein.

[0108] In some embodiments, B is [ka] is selected from.

[0109] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] is.

[0110] As outlined for formulas (I), (II), (III), (IV), (V), (VI), (VII), (VIII), and (IX), L 1 and L 2 each is independently absent or C-C-alkylene, C-C-heteroalkylene, —O—, —C(O)—, —N(R 8 )-, -N(R 8 )C(O)- or -C(O)N(R 8 )-group, where each alkylene and heteroalkylene can be one or more R 9 In some embodiments, L 1is absent or C1-C6-heteroalkylene. 1 is absent. In some embodiments, L 1 is C1-C6-heteroalkylene (e.g., -N(CH3)-). In some embodiments, L 2 is absent or C1-C6-heteroalkylene. 2 is absent. In some embodiments, L 2 is C1-C6-heteroalkylene (e.g., -N(CH3)-).

[0111] As outlined for formula (I), each of W, X, and Z is independently N or C(R 3 In some embodiments, W can be C(R 3 ) (e.g., CH). In some embodiments, W is N. In some embodiments, X is C(R 3 ) (e.g., CH). In some embodiments, X is N. In some embodiments, Z is C(R 3 ) (e.g., CH). In some embodiments, Z is N. In some embodiments, each of W and X is independently C(R 3 ) (e.g., CH). In some embodiments, each of W and Z is independently C(R 3 ) (e.g., CH). In some embodiments, each of X and Z is independently C(R 3 ) (e.g., CH). In some embodiments, each of W, X, and Z is independently C(R 3 ) (e.g., CH).

[0112] As outlined for formula (I), Y is N, N(R 4a ), C(R 4b ), or C(R 4b )(R 4c), where the dashed line in the ring containing Y can be a single or double bond, valence permitting. In some embodiments, Y can be N(R 4a ) or C(R 4b In some embodiments, Y is N(R 4a ) (e.g., NH). In some embodiments, Y is C(R 4b ) (e.g., CH).

[0113] In some embodiments, W is C(R 3 ) and Y is N(R 4a In some embodiments, W is CH and Y is NH. In some embodiments, X is C(R 3 ) and Y is N(R 4a In some embodiments, X is CH and Y is NH. In some embodiments, Z is C(R 3 ) and Y is N(R 4a In some embodiments, Z is CH and Y is NH. In some embodiments, W and Z are independently C(R 3 ) and Y is N(R 4a In some embodiments, W and X are independently C(R 3 ) and Y is NH. In some embodiments, W and Z are independently C(R 3 ) and Y is N(R 4a In some embodiments, W and Z are independently C(R 3 ) and Y is NH. In some embodiments, X and Z are independently C(R 3 ) and Y is N(R 4a In some embodiments, X and Z are independently C(R 3 ) and Y is NH. In some embodiments, each of W, X, and Z is independently C(R 3 ) and Y is N(R 4aIn some embodiments, each of W, X, and Z is independently CH and Y is NH.

[0114] In some embodiments, W is C(R 3 ) and Y is N. In some embodiments, W is CH and Y is N. In some embodiments, X is C(R 3 ) and Y is N. In some embodiments, X is CH and Y is N. In some embodiments, Z is C(R 3 ) and Y is N. In some embodiments, Z is CH and Y is N. In some embodiments, W and X are independently C(R 3 ) and Y is N. In some embodiments, W and X are independently C(R 3 ) and Y is N. In some embodiments, W and Z are independently C(R 3 ) and Y is N. In some embodiments, W and Z are independently C(R 3 ) and Y is N. In some embodiments, X and Z are independently C(R 3 ) and Y is N. In some embodiments, X and Z are independently C(R 3 ) and Y is N. In some embodiments, each of W, X, and Z is independently C(R 3 ) and Y is N. In some embodiments, each of W, X, and Z is independently CH and Y is N.

[0115] In some embodiments, R 2 is absent.

[0116] In some embodiments, R 1 is C1-C6-alkyl. In some embodiments, R 1 In some embodiments, A is 0 or 1 R 1In some embodiments, B is substituted with 0, 1, or 2 R 1 is replaced by

[0117] In some embodiments of Formula (II), A is bicyclic heteroaryl and B is monocyclic heterocyclyl. In some embodiments of Formula (II), Z is N. In some embodiments of Formula (II), each of W, X, and Z is independently C(R 3 ), e.g., is not (CH). In some embodiments of Formula (II), the compound is not a compound disclosed in WO2020 / 004594.

[0118] In some embodiments, for Formula (III), A is a bicyclic heteroaryl that does not contain oxygen. In some embodiments, A is one or more R 1 and bicyclic heteroaryl substituted by 1 is not halo. In some embodiments, A is [ka] isn't it.

[0119] In some embodiments, B is one or more R 1 is a nitrogen-containing heterocyclyl optionally substituted by 1 is not cycloalkyl (e.g., cyclopropyl). In some embodiments, B is unsubstituted piperidinyl (e.g., R 1 In some embodiments, B is [ka] Instead, in the formula, R 1 is C1-C6 alkyl (e.g., methyl) or cycloalkyl (e.g., cyclopropyl). In some embodiments, B is [ka] where R 1 is hydrogen. In some embodiments, B is [ka] In some embodiments, B is not [ka] isn't it.

[0120] In some embodiments, X is C(R 3 ) where R 3 is halo. In some embodiments, X is CF.

[0121] In some embodiments, the compound of formula (III) is not a compound disclosed in WO2020 / 004594. In some embodiments, the compound of formula (III) is [ka] or a pharmaceutically acceptable salt thereof.

[0122] In some embodiments, the present disclosure provides a compound of formula (Ii): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 and optionally replaced by L 1 and L 2 each independently represents absence, C-C-alkylene, C-C-heteroalkylene, —O—, —C(O)—, —N(R 4 )-, -N(R 4 )C(O)-, or -C(O)N(R 4)-, where each alkylene and heteroalkylene is selected from one or more R 7 and Y is optionally substituted with N, C(R 6a ), or C(R 6a )(R 6b ), where the dashed line in the ring containing Y can be a single or double bond, valence permitting, and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -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 selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 and each R 2 are independently hydrogen or C1-C6-alkyl, R 3 is C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D, or -C(O)OR D and R 4 is hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 optionally replaced by R 6a and R 6b are independently hydrogen, C-C-alkyl, C-C-heteroalkyl, C-C-haloalkyl, or halo, and each R 7 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A are independently hydrogen, C-C alkyl, C-C haloalkyl, aryl, heteroaryl, C-C alkylene-aryl, C-C alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, -OR A or R B and R Ctogether with the atoms to which they are attached form one or more R 9 and each R D are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 9 is independently C1-C6-alkyl or halo, n is 0, 1 or 2, m is 0, 1, 2 or 3 and x is 0, 1 or 2.

[0123] In some embodiments, A is one or more R 1 In some embodiments, A is a monocyclic nitrogen-containing heterocyclyl. In some embodiments, A is an optionally substituted piperidinyl. In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0124] In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0125] In some embodiments, A is [ka] is selected from.

[0126] In some embodiments, A is heteroaryl. In some embodiments, A is a nitrogen-containing heteroaryl. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl.

[0127] In some embodiments, A is [ka] In some embodiments, A is selected from: [ka] where R 1 is as defined herein. In some embodiments, A is [ka] is selected from.

[0128] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] is.

[0129] In some embodiments, B is heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] In some embodiments, B is selected from: [ka] where R 1 is as defined herein.

[0130] In some embodiments, B is [ka] is selected from.

[0131] In some embodiments, B is heterocyclyl. In some embodiments, B is nitrogen-containing heterocyclyl. In some embodiments, B is monocyclic nitrogen-containing heterocyclyl or bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1 is as defined herein.

[0132] In some embodiments, B is [ka] is selected from.

[0133] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] is.

[0134] In some embodiments, the compound of Formula (I) has the formula (Ia): [ka] 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 selected from the group consisting of one or more R 1 and optionally replaced by L1 are independently absent, C-C-alkylene, C-C-heteroalkylene, -O-, -C(O)-, -N(R 4 )-, -N(R 4 )C(O)-, or -C(O)N(R 4 )-, where each alkylene and heteroalkylene is selected from one or more R 7 and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -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 selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 and each R 2 are independently hydrogen or C1-C6-alkyl, R 3 is C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B RC , -C(O)R D , or -C(O)OR D and R 4 is hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 7 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A are independently hydrogen, C-C alkyl, C-C haloalkyl, aryl, heteroaryl, C-C alkylene-aryl, C-C alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, -OR A or R B and R C together with the atoms to which they are attached form one or more R 9and each R D are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 9 is independently C1-C6-alkyl or halo, n is 0, 1 or 2 and x is 0, 1 or 2.

[0135] In some embodiments, A is one or more R 1 In some embodiments, A is a monocyclic nitrogen-containing heterocyclyl. In some embodiments, A is an optionally substituted piperidinyl. In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0136] In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0137] In some embodiments, A is [ka] is selected from.

[0138] In some embodiments, A is heteroaryl. In some embodiments, A is a nitrogen-containing heteroaryl. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl.

[0139] In some embodiments, A is [ka] In some embodiments, A is selected from: [ka] where R 1 is as defined herein. In some embodiments, A is [ka] is selected from.

[0140] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] Some In an embodiment, A is [ka] is.

[0141] In some embodiments, B is heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] In some embodiments, B is selected from: [ka] where R 1 is as defined herein.

[0142] In some embodiments, B is [ka] is selected from.

[0143] In some embodiments, B is heterocyclyl. In some embodiments, B is nitrogen-containing heterocyclyl. In some embodiments, B is monocyclic nitrogen-containing heterocyclyl or bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1 is as defined herein.

[0144] In some embodiments, B is [ka] is selected from.

[0145] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] is.

[0146] In some embodiments, the compound of Formula (I) has the formula (Ib): [ka] 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 selected from the group consisting of one or more R 1 and optionally replaced by L 1 are independently absent, C-C-alkylene, C-C-heteroalkylene, -O-, -C(O)-, -N(R 4 )-, -N(R 4)C(O)-, or -C(O)N(R 4 )-, where each alkylene and heteroalkylene is selected from one or more R 7 and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -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 selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 and each R 2 are independently hydrogen or C1-C6-alkyl, R 3 is C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and R 4is hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 7 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A are independently hydrogen, C-C alkyl, C-C haloalkyl, aryl, heteroaryl, C-C alkylene-aryl, C-C alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, -OR A or R B and R C together with the atoms to which they are attached form one or more R 9 and each R Dare independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 9 is independently C1-C6-alkyl or halo, m is 0, 1, 2, or 3, and x is 0, 1, or 2.

[0147] In some embodiments, A is one or more R 1 In some embodiments, A is a monocyclic nitrogen-containing heterocyclyl. In some embodiments, A is an optionally substituted piperidinyl. In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0148] In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0149] In some embodiments, A is [ka] is selected from.

[0150] In some embodiments, A is heteroaryl. In some embodiments, A is a nitrogen-containing heteroaryl. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl.

[0151] In some embodiments, A is [ka] In some embodiments, A is selected from: [ka] where R 1 is as defined herein. In some embodiments, A is [ka] is selected from.

[0152] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] is.

[0153] In some embodiments, B is heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] In some embodiments, B is selected from: [ka] where R 1 is as defined herein.

[0154] In some embodiments, B is [ka] is selected from.

[0155] In some embodiments, B is heterocyclyl. In some embodiments, B is nitrogen-containing heterocyclyl. In some embodiments, B is monocyclic nitrogen-containing heterocyclyl or bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1is as defined herein. In some embodiments, B is [ka] wherein R 1 is as defined herein.

[0156] In some embodiments, B is [ka] is selected from.

[0157] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] is.

[0158] In some embodiments, the compound of Formula (I) has the formula (Ic): [ka] 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 selected from the group consisting of one or more R 1 and optionally replaced by L 1 are independently absent, C-C-alkylene, C-C-heteroalkylene, -O-, -C(O)-, -N(R 4 )-, -N(R 4 )C(O)-, or -C(O)N(R 4 )-, where each alkylene and heteroalkylene is selected from one or more R7 and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -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 selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 and each R 2 are independently hydrogen or C1-C6-alkyl, R 3 is C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and R 4 is hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 7 and each R 7 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A are independently hydrogen, C-C alkyl, C-C haloalkyl, aryl, heteroaryl, C-C alkylene-aryl, C-C alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, -OR A or R B and R C together with the atoms to which they are attached form one or more R 9 and each R Dare independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 9 is independently C1-C6-alkyl or halo, n is 0, 1 or 2, m is 0, 1, 2 or 3 and x is 0, 1 or 2.

[0159] In some embodiments, A is one or more R 1 In some embodiments, A is a monocyclic nitrogen-containing heterocyclyl. In some embodiments, A is an optionally substituted piperidinyl. In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0160] In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0161] In some embodiments, A is [ka] is selected from.

[0162] In some embodiments, A is heteroaryl. In some embodiments, A is a nitrogen-containing heteroaryl. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl.

[0163] In some embodiments, A is [ka] In some embodiments, A is selected from: [ka] where R 1 is as defined herein. In some embodiments, A is [ka] is selected from.

[0164] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] is.

[0165] In some embodiments, B is heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] In some embodiments, B is selected from: [ka] where R 1 is as defined herein.

[0166] In some embodiments, B is [ka] is selected from.

[0167] In some embodiments, B is heterocyclyl. In some embodiments, B is nitrogen-containing heterocyclyl. In some embodiments, B is monocyclic nitrogen-containing heterocyclyl or bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1 is as defined herein.

[0168] In some embodiments, B is [ka] is selected from.

[0169] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] is.

[0170] In some embodiments, the compound of Formula (I) is selected from the compounds in Table 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] Table 1-6 Table 1-7 Table 1-8 Table 1-9 Table 1-10 Table 1-11 Table 1-12 Table 1-13 Table 1-14 Table 1-15 Table 1-16 Table 1-17 Table 1-18 Table 1-19 Table 1-20 Table 1-21 Table 1-22 [Table 1-23] [Table 1-24] [Table 1-25] [Table 1-26]

[0171] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 185, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0172] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 186, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0173] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 2. In some embodiments, the compound of Formula (I) is compound 187, 188, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0174] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 4-fluoro-2-methylbenzo[d]oxazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 215, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0175] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 216, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0176] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 217, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0177] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,7-dimethylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 218, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0178] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 219, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0179] In some embodiments, for Formula (I), A is monocyclic heteroaryl (e.g., pyrazolyl), B is monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 220, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0180] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 6,8-dimethylimidazo[1,2-a]pyrazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 221, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0181] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 6,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 222, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0182] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 4,6-dimethylpyrazolo[1,5-a]pyrazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 223, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0183] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methylimidazo[1,2-a]pyrazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 224, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0184] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R6b ) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 225, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0185] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 4-fluoro-2-methylbenzo[d]thiazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 226, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0186] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 247, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0187] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 248, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0188] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 249, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0189] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 4-fluoro-2-methylbenzo[d]oxazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 250, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0190] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 251, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0191] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH2), and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 252, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0192] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 4-fluoro-2-methylbenzo[d]thiazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 253, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0193] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,7-dimethylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 254, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0194] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methylimidazo[1,2-a]pyrazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 255, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0195] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 256, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0196] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 257, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0197] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 6,8-dimethylimidazo[1,2-a]pyrazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 258, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0198] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 6,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 259, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0199] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 4,6-dimethylpyrazolo[1,5-a]pyrazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 260, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0200] In some embodiments, for Formula (I), A is monocyclic heteroaryl (e.g., pyrazyl), B is monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 261, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0201] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 262, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0202] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 263, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0203] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl), and L 1 and L 2is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 264, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0204] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 265, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0205] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-ethylpiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 266, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0206] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., 2,2-dimethylpiperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 267, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0207] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 268, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0208] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 269, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0209] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-ethylpiperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 270, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0210] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-methylpyrrolidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 271, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0211] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., 2-methylpiperidine), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 272, 273, 324, 328, 329, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0212] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 274, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0213] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., tetrahydro-2H-pyranyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 275, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0214] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 276, 403, 404, 578, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0215] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-methyl 2-methylpiperidine), and L 1 and L 2 is absent, Y is N, and R 2is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 277, 278, 325, 330, 331, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0216] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., 2,2-dimethylpiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 279, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0217] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., 8-azabicyclo[3.2.1]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 280, 326, 332, 333, 334, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0218] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., 2-methylpiperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 281, 327, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0219] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-methylpyrrolidinyl), and L 1 and L 2 is absent, and Y is C(R 6a )(R 6b ) (e.g., CH), and each R 2 is hydrogen, m is 0, and n is 2. In some embodiments, the compound of Formula (I) is compound 282, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0220] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., azepanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 283, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0221] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., 2-ethylpiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 304, 305, 328, 335, 336, 567, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0222] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 309, 410, 411, 579, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0223] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen, m is 0, and n is 1. In some embodiments, the compound of Formula (I) is compound 310, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0224] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 312, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0225] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 322, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0226] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., 2-methylpiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 and R 3 are independently hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is Compound 324, Compound 328, Compound 329, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0227] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., 1,2-dimethylpiperidinyl), and L 1 and L 2 is absent, Y is N, and R2 and R 3 are independently hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is Compound 325, Compound 330, Compound 331, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0228] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a bicyclic heterocyclyl (e.g., 8-azabicyclo[3.2.1]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 and R 3 are independently hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 326, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0229] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., 2-methylpiperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH2), and R 2 and R 3 are independently hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is Compound 327, Compound 332, Compound 333, Compound 334, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0230] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., 2-ethylpiperidinyl), and L 1and L 2 is absent, Y is N, and R 2 and R 3 are independently hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is Compound 335, Compound 336, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0231] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is Compound 368, Compound 369, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0232] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 370, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0233] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., 3-fluoropiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 372, 568, 569, 570, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0234] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-imidazolyl), B is a bicyclic heterocyclyl (e.g., 2-oxa-5-azaspiro[3.5]nonanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 375, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0235] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-imidazolyl), B is a monocyclic heterocyclyl (e.g., 3-fluoropiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 378, 571, 572, 573, 574, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0236] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-b]pyridazinyl), B is a monocyclic heterocyclyl (e.g., 3-fluoropiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 379, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0237] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is Compound 380, Compound 425, Compound 426, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0238] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is methyl and R 3is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 381, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0239] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazinyl), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is Compound 382, ​​Compound 392, 575, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0240] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-cyano-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 383, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0241] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2is absent, and Y is C(R 6a ) (e.g., CH) and R 2 and R 3 are each hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 384 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0242] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is cyano, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 387, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0243] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., Cl), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 390, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0244] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydroxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is Compound 391, Compound 448, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0245] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 1-(2-methylimidazo[1,2-a]pyridin-8-yl)ethanoyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 393, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0246] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 7-cyano-2-methyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 394, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0247] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is Compound 395, Compound 396, 576, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0248] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is methyl, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is Compound 397, Compound 398, 577, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0249] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is methoxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 399, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0250] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 400, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0251] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-ethylpiperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 401, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0252] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-ethylpiperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 402, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0253] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is methylsulfonyl, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 409, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0254] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 412, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0255] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 7-chloro-2-methyl-2H-indazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 413, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0256] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 6-hydroxy-2-methyl-2H-indazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 414, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0257] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 415, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0258] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-a]pyridinyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 416, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0259] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 4-fluoro-2-methyl-1,3-benzoxazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 417, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0260] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,4-dimethylbenzoxazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 418, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0261] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 6-hydroxy-2,4-dimethyl-2H-indazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 419, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0262] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 7-fluoro-6-hydroxy-2-methyl-2H-indazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 420, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0263] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 6-hydroxy-2,7-dimethyl-2H-indazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 421, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0264] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is methyl, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 423, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0265] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methylimidazo[1,2-a]pyrazinyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 428, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0266] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 1,2,4-trimethyl-1H-benzimidazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 429, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0267] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 4-fluoro-1,2-dimethyl-1H-benzimidazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 430, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0268] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,7-dimethylpyrazolo[4,3-b]pyridinyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 431, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0269] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydroxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 432, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0270] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-cyano-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3is hydroxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 433, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0271] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., 8-cyano-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 434, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0272] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is methyl and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 440, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0273] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl), and L 1 and L 2 is absent, and Y is C(R 6a) (e.g., CH) and R 2 is methyl and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 441, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0274] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-cyano-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is methyl and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 442, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0275] In some embodiments, for Formula (V), A is a bicyclic heteroaryl (e.g., 8-cyano-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH2), and R 2 is hydrogen and R 3 is hydroxyl, m is 1, and n is 2. In some embodiments, the compound of Formula (I) is compound 443, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0276] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazinyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 444, compound 445, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0277] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazinyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is halo (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is Compound 446, Compound 447, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0278] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a bicyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydroxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 448, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0279] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is methoxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 449, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0280] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is methyl and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 451, compound 452, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0281] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 453, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0282] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl), B is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-a]pyrazinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 454, 580, 581, 582, 583, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0283] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-cyano-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is methyl and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 456, compound 457, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0284] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is methyl and R 3 is halogen (e.g., F), m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 461, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0285] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is methyl and R 3 is hydroxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 462, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0286] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydroxyl, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 466, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0287] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is methyl, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is Compound 467, Compound 468, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0288] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydroxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 469, compound 470, 584, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0289] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a bicyclic heterocyclylamino (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 471, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0290] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a secondary amino (e.g., ethylmethylamino), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 472, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0291] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a secondary amino (e.g., N,N-dimethylethylamino), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 473, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0292] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 474, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0293] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-cyano-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 475, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0294] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 476, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0295] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 7-fluoro-6-hydroxy-2-methyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a) (e.g., CH) and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 477, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0296] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-6-hydroxy-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 478, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0297] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 479, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0298] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 480, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0299] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 481, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0300] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methyl-2,4,6,7-tetrahydro-5-pyrazolo[4,3-c]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 509, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0301] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl), B is a bicyclic heterocyclylamino (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 510, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0302] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methyl-2H-pyrazolo[4,3-b]pyridinyl), B is a bicyclic heterocyclylamino (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 511, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0303] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), B is a bicyclic heterocyclylamino (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 512, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0304] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,4-dimethylbenzo[d]oxazolyl), B is a bicyclic heterocyclylamino (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 513, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0305] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-methoxy-2-methylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 514, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0306] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-(1-fluoro)-ethylpiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydrogen, m is 1, 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.

[0307] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methylimidazo[1,2-b]pyridazyl-8-carboxylic acid), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, 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.

[0308] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methylimidazo[1,2-b]pyridazyl-8-carboxylate), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, 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.

[0309] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., N,2-methylimidazo[1,2-b]pyridazyl-8-carboxamide), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 518, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0310] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methyl-8-phenoxyimidazo[1,2-b]pyridazinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 519, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0311] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-(2-methylimidazo[1,2-b]pyridazin-8-yl)acetonitrile), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 520, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0312] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 5-methyl-1-pyrazolo[4,5-c]pyridin-4(5H)-one), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 521, 522, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0313] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methylimidazo[1,2-b]pyridazyl-8-carboxamide), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 523, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0314] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., N,N,2-methylimidazo[1,2-b]pyridazyl-8-carboxamide), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 524, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0315] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., (2-methylimidazo[1,2-b]pyridazin-8-yl)methanol), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 525, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0316] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., (8-(benzyloxy)-2-methylimidazo[1,2-b]pyridazinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 526, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0317] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., methyl (2-(2-methylimidazo[1,2-b]pyridazin-8-yl)acetate), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 527, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0318] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., (2-(2-methylimidazo[1,2-b]pyridazin-8-yl)acetamide), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 528, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0319] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., ethyl 2-methylimidazo[1,2-b]pyridazine-8-carboxylate), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 529, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0320] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methyl-5-pyrazolo[4,3-c]pyridin-4(2H)-one), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 530, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0321] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-(2-methylimidazo[1,2-b]pyridazin-8-yl)acetic acid), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 531, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0322] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., N,N-dimethyl-2-(2-methylimidazo[1,2-b]pyridazin-8-yl)acetamide), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 532, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0323] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-(2-methylimidazo[1,2-b]pyridazin-8-yl)ethan-1-ol), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 533, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0324] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., N-methyl-2-(2-methylimidazo[1,2-b]pyridazin-8-yl)acetamide), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 534, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0325] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-((4H-1,2,4-triazol-3-yl)methyl)-2-methylimidazo[1,2-b]pyridazinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 535, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0326] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-((1H-tetrazol-5-yl)methyl)-2-methylimidazo[1,2-b]pyridazinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 536, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0327] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-ethylpiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 537, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0328] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-(1-fluoro)-ethylpiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 538, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0329] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 539, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0330] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 540, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0331] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3is hydroxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 541, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0332] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-ethylpiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydroxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 542, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0333] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydroxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 543, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0334] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-(2-fluorophenoxy)-2-methylimidazo[1,2-b]pyridazinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 544, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0335] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-(3-fluorophenoxy)-2-methylimidazo[1,2-b]pyridazinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 545, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0336] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-(4-fluorophenoxy)-2-methylimidazo[1,2-b]pyridazinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 546, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0337] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-(3-methoxyphenoxy)-2-methylimidazo[1,2-b]pyridazinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 547, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0338] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-phenoxy-2-methylimidazo[1,2-b]pyridazinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 548, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0339] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-phenoxy-2-methylimidazo[1,2-b]pyridazinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 549, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0340] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methyl-8-(pyridin-3-yloxy)imidazo[1,2-b]pyridazinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 550, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0341] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 1-(2-methylimidazo[1,2-b]pyridazin-8-yl)pyridin-4(1H)-one), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 551, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0342] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 1-(2-methylimidazo[1,2-b]pyridazin-8-yl)pyridin-2(1H)-one), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 552, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0343] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-(1-fluoro)-ethylpiperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydroxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 553, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0344] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 554, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0345] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,4-dimethylbenzo[d]oxazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 555, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0346] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 556, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0347] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydroxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 557, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0348] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is ethyl, and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 558, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0349] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is vinyl and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 559, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0350] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 8-cyano-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and Y is C(R 6a ) (e.g., CH) and R 2 is hydrogen and R 3 is hydrogen, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 560, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0351] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3is hydroxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 561, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0352] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methyl-2H-pyrazolo[4,3-b]pyridinyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is hydroxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 562, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0353] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2-methyl-2H-pyrazolo[4,3-b]pyridinyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 563, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0354] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,4-dimethylbenzo[d]oxazolyl), B is a bicyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3is hydroxy, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 564, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0355] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a bicyclic heterocyclyl (e.g., N-methyl-4-azaspiro[2.5]octanyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is fluoro, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 565, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0356] In some embodiments, for Formula (I), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, Y is N, and R 2 is hydrogen and R 3 is amino, m is 1, and n is 1. In some embodiments, the compound of Formula (I) is compound 566, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0357] In some embodiments, the compound of formula (II) is a compound of formula (II-a): [ka] 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 may contain one or more R 1 and optionally replaced by L 1 is absent, C1-C6-alkylene, C1-C6-heteroalkylene, -O-, -C(O)-, -N(R 8 )-, -N(R 8 )C(O)-, or -C(O)N(R 8 )-, where each alkylene and heteroalkylene is selected from one or more R 9 and each of W, X, and Z is independently C(R 3 ) or N, and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -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 selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5optionally replaced by R 3 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D and R 4a is hydrogen, C-C-alkyl, C-C-heteroalkyl, or C-C-haloalkyl, and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 and each R 6 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R 8 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 9 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, halo, cyano, oxo, -OR A , -NRB R C , -C(O)R D , or -C(O)OR D and each R A are independently hydrogen, C-C alkyl, C-C haloalkyl, aryl, heteroaryl, C-C alkylene-aryl, C-C alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, -OR A or R B and R C together with the atoms to which they are attached form one or more R 10 and each R D are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 10 is independently C1-C6-alkyl or halo, and x is 0, 1, or 2.

[0358] In some embodiments, A is one or more R 1 In some embodiments, A is a monocyclic nitrogen-containing heterocyclyl. In some embodiments, A is an optionally substituted piperidinyl. In some embodiments, A is [ka] wherein R 1 is as defined herein. In some embodiments, A is [ka] wherein R 1 is as defined herein. In some embodiments, A is [ka] is selected from.

[0359] In some embodiments, A is heteroaryl. In some embodiments, A is a nitrogen-containing heteroaryl. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl.

[0360] In some embodiments, A is [ka] In some embodiments, A is selected from: [ka] where R 1 is as defined herein. In some embodiments, A is [ka] is selected from.

[0361] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] is.

[0362] In some embodiments, B is heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] In some embodiments, B is selected from: [ka] where R 1 is as defined herein.

[0363] In some embodiments, B is [ka] is selected from.

[0364] In some embodiments, B is heterocyclyl. In some embodiments, B is nitrogen-containing heterocyclyl. In some embodiments, B is monocyclic nitrogen-containing heterocyclyl or bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1 is as defined herein.

[0365] In some embodiments, B is [ka] is selected from.

[0366] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] is.

[0367] In some embodiments, L 1is absent or N(CH). In some embodiments, L 1 is absent. In some embodiments, L 1 is N(CH3).

[0368] In some embodiments, each of W, X, and Z is independently N or C(R 3 In some embodiments, W can be C(R 3 ) (e.g., CH). In some embodiments, W is N. In some embodiments, X is C(R 3 ) (e.g., CH). In some embodiments, X is N. In some embodiments, Z is C(R 3 ) (e.g., CH). In some embodiments, Z is N. In some embodiments, each of W and X is independently C(R 3 ) (e.g., CH). In some embodiments, each of W and Z is independently C(R 3 ) (e.g., CH). In some embodiments, each of X and Z is independently C(R 3 ) (e.g., CH). In some embodiments, each of W, X, and Z is independently C(R 3 ) (e.g., CH).

[0369] In some embodiments, R 4a is hydrogen or C1-C6 alkyl. In some embodiments, R 4a is hydrogen.

[0370] In some embodiments, R 1 is C1-C6-alkyl. In some embodiments, R 1 In some embodiments, A is 0 or 1 R 1 In some embodiments, B is substituted with 0, 1, or 2 R 1 is replaced by

[0371] In some embodiments, A is bicyclic heteroaryl and B is monocyclic heterocyclyl. In some embodiments of Formula (II), Z is N. In some embodiments of Formula (II), each of W, X, and Z is independently C(R 3 ), e.g., not (CH).

[0372] In some embodiments, the compound of Formula (II) is a compound of Formula (II-b): [ka] 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 selected from the group consisting of one or more R 1 and Y is optionally substituted with N, N(R 4a ), C(R 4b ), or C(R 4b )(R 4c ), where the dashed line in the ring containing Y can be a single or double bond, valence permitting, and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R Dwherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 optionally replaced by R 2 is absent, hydrogen, or C1-C6-alkyl, and R 4a is hydrogen, C-C-alkyl, C-C-heteroalkyl, or C-C-haloalkyl, and R 4b and R 4c each independently represents hydrogen, C-C-alkyl, C-C-heteroalkyl, C-C-haloalkyl, halo, or -OR A and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 and each R 6are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A are independently hydrogen, C-C alkyl, C-C haloalkyl, aryl, heteroaryl, C-C alkylene-aryl, C-C alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, -OR A or R B and R C together with the atoms to which they are attached form one or more R 10 and each R D are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 10 is independently C1-C6-alkyl or halo, and x is 0, 1, or 2.

[0373] In some embodiments, A is one or more R 1 In some embodiments, A is a monocyclic nitrogen-containing heterocyclyl. In some embodiments, A is an optionally substituted piperidinyl. In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0374] In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0375] In some embodiments, A is [ka] is selected from.

[0376] In some embodiments, A is heteroaryl. In some embodiments, A is a nitrogen-containing heteroaryl. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl.

[0377] In some embodiments, A is [ka] In some embodiments, A is selected from: [ka] where R 1 is as defined herein. In some embodiments, A is [ka] is selected from.

[0378] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] is.

[0379] In some embodiments, B is heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] In some embodiments, B is selected from: [ka] where R 1 is as defined herein.

[0380] In some embodiments, B is [ka] is selected from.

[0381] In some embodiments, B is heterocyclyl. In some embodiments, B is nitrogen-containing heterocyclyl. In some embodiments, B is monocyclic nitrogen-containing heterocyclyl or bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1 is as defined herein.

[0382] In some embodiments, B is [ka] is selected from.

[0383] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] is.

[0384] As outlined, Y is a function of N, N(R 4a ), C(R 4b ), or C(R 4b )(R 4c ), where the dashed line in the ring containing Y can be a single or double bond, valence permitting. In some embodiments, Y can be N(R 4a ) or C(R 4b In some embodiments, Y is N(R 4a ) (e.g., NH). In some embodiments, Y is C(R 4b ) (e.g., CH).

[0385] In some embodiments, R 2 is absent.

[0386] In some embodiments, R 1 is C1-C6-alkyl. In some embodiments, R 1 In some embodiments, A is 0 or 1 R 1 In some embodiments, B is substituted with 0, 1, or 2 R 1 In some embodiments, A is a bicyclic heteroaryl and B is a monocyclic heterocyclyl.

[0387] In some embodiments, the compound of Formula (II) is a compound of Formula (II-c): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A is one or more R 1 and B is a monocyclic nitrogen-containing heterocyclyl optionally substituted with one or more R 1wherein each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -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 selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R Dwherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 optionally replaced by R 4a is hydrogen, C-C-alkyl, C-C-heteroalkyl, or C-C-haloalkyl, and each R 6 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A are independently hydrogen, C-C alkyl, C-C haloalkyl, aryl, heteroaryl, C-C alkylene-aryl, C-C alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, -OR A or R B and R C together with the atoms to which they are attached form one or more R 10 and each R D are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 10 is independently C1-C6-alkyl or halo, and x is 0, 1, or 2.

[0388] In some embodiments, A is one or more R 1In some embodiments, A is a monocyclic nitrogen-containing heterocyclyl. In some embodiments, A is an optionally substituted piperidinyl. In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0389] In some embodiments, A is [ka] wherein R 1 is as defined herein.

[0390] In some embodiments, A is [ka] is selected from.

[0391] In some embodiments, A is heteroaryl. In some embodiments, A is a nitrogen-containing heteroaryl. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl.

[0392] In some embodiments, A is [ka] In some embodiments, A is selected from: [ka] where R 1 is as defined herein. In some embodiments, A is [ka] is selected from.

[0393] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] is.

[0394] In some embodiments, B is heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] In some embodiments, B is selected from: [ka] where R 1 is as defined herein.

[0395] In some embodiments, B is [ka] is selected from.

[0396] In some embodiments, B is heterocyclyl. In some embodiments, B is nitrogen-containing heterocyclyl. In some embodiments, B is monocyclic nitrogen-containing heterocyclyl or bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1 is as defined herein. In some embodiments, B is [ka] wherein R 1 is as defined herein.

[0397] In some embodiments, B is [ka] is selected from.

[0398] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] is.

[0399] In some embodiments, R 1 is C1-C6-alkyl. In some embodiments, R 1 In some embodiments, A is 0 or 1 R 1 In some embodiments, B is substituted with 0, 1, or 2 R 1 is replaced by

[0400] In some embodiments, the compound of Formula (II) is selected from the compounds in Table 2, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4] [Table 2-5] [Table 2-6]

[0401] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 100, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0402] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 101, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0403] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 102, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0404] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 103, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0405] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 104, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0406] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 105, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0407] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 106, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0408] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 107, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0409] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperazinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 108, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0410] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperazinyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 109, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0411] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperazinyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 110, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0412] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 111, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0413] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 112, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0414] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 113, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0415] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 114, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0416] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 115, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0417] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 116, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0418] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 117, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0419] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 118, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0420] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 119, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0421] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 is -N(R 8 )-(e.g., -N(CH3)-), and L 2 is absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is Compound 120, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0422] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), and L 1 is -N(R 8 )-(e.g., -N(CH3)-), and L 2 is absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 121, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0423] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), and L 1 is -N(R 8 )-(e.g., -N(CH3)-); and L 2is absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 122, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0424] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 1 is -N(R 8 )-(e.g., -N(CH3)-), and L 2 is absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 123, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0425] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 124, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0426] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 125, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0427] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 126, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0428] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 127, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0429] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 128, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0430] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 129, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0431] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), and L 1 and L2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is Compound 130, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0432] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 131, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0433] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 132, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0434] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 133, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0435] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 134, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0436] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 135, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0437] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperazyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 136, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0438] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperazyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 137, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0439] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperazyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), and L 1 and L 2are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 138, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0440] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperazyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 139, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0441] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 140, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0442] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 141, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0443] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 142, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0444] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 1 and L 2 are each absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 143, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0445] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 is -N(R 8 )-(e.g., -N(CH3)-), and L 2 is absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 144, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0446] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), and L 1 is -N(R 8 )-(e.g., -N(CH3)-), and L 2 is absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 145, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0447] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), and L 1 is -N(R 8 )-(e.g., -N(CH3)-), and L 2 is absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 146, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0448] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 1 is -N(R 8 )-(e.g., -N(CH3)-), and L 2 is absent, and X and W are each independently C(R 3 ) (e.g., CH), Z is N, and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) and (II-a) is compound 147, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0449] In some embodiments, for Formula (II), A is a bicyclic heterocyclyl (e.g., 2,7-dimethyl-2H-indazolyl), B is a monocyclic heteroaryl (e.g., N-methylpiperazyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 165, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0450] In some embodiments, for Formula (II), A is a bicyclic heterocyclyl (e.g., 2,7-dimethyl-2H-indazolyl), B is a monocyclic heteroaryl (e.g., piperazyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 166, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0451] In some embodiments, for Formula (II), A is a bicyclic heterocyclyl (e.g., 2,7-dimethyl-2H-indazolyl), B is a monocyclic heteroaryl (e.g., N-methylpiperidinyl), and L 1 is absent, L 2 is -N(R 8 )—(e.g., —N(H)—), and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 167, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0452] In some embodiments, for Formula (II), A is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl), B is a monocyclic heteroaryl (e.g., piperidinyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 189, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0453] In some embodiments, for Formula (II), A is a bicyclic heterocyclyl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heteroaryl (e.g., 4,7-diazaspiro[2.5]octanyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 190, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0454] In some embodiments, for Formula (II), A is a bicyclic heterocyclyl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heteroaryl (e.g., 4,7-diazaspiro[2.5]octanyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 191, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0455] In some embodiments, for Formula (II), A is a bicyclic heterocyclyl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heteroaryl (e.g., piperidinyl), and L 1 is absent, L 2 is -N(R 8 )—(e.g., —N(H)—), and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) is compound 192, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0456] In some embodiments, for Formula (II), A is a bicyclic heterocyclyl (e.g., 5-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heteroaryl (e.g., piperidinyl), and L 1 is absent, L 2 is -N(R 8 )—(e.g., —N(H)—), and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) is compound 193, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0457] In some embodiments, for Formula (II), A is a bicyclic heterocyclyl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heteroaryl (e.g., piperidinyl), and L 1 is absent, L 2 is -N(R 8 )—(e.g., —N(H)—), and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II) is compound 238, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0458] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), and L 1 is -N(R 8 )-(e.g., -N(CH3)-), and L 2 is absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 239, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0459] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazinyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 483, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0460] In some embodiments, for Formula (II), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazinyl), and L 1 and L 2 are each absent, and X, W, and Z are each independently C(R 3 ) (e.g., CH), and Y is N(R 4a ) (e.g., NH) and R 2 is absent. In some embodiments, the compound of Formula (II), (II-a), (II-b), and (II-c) is compound 484, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0461] As outlined for formula (III), Y is N, C, or C(R b ), where the dashed line in the ring containing Y can be a single or double bond, valence permitting. In some embodiments, Y is N or C. In some embodiments, Y is N (e.g., N). In some embodiments, Y is C.

[0462] In some embodiments, Z is C(R 3 ) and Y is N. In some embodiments, Z is CH and Y is N. In some embodiments, X is C(R 3 ) and Y is N. In some embodiments, X is CH and Y is N. In some embodiments, Z is C(R 3) and Y is N. In some embodiments, Z is CH and Y is N. In some embodiments, Z and X are independently C(R 3 ) and Y is N. In some embodiments, Z and X are independently CH and Y is N. In some embodiments, X and Z are independently C(R 3 ) and Y is N. In some embodiments, X and Z are independently C(R 3 ) and Y is N. In some embodiments, X and Z are independently CH and Y is N.

[0463] In some embodiments, the compound of formula (III) is a compound of formula (III-a): [ka] 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 selected from the group consisting of one or more R 1 and optionally replaced by L 1 is absent, C1-C6-alkylene, C1-C6-heteroalkylene, -O-, -C(O)-, -N(R 8 )-, -N(R 8 )C(O)-, or -C(O)N(R 8 )-, where each alkylene and heteroalkylene is selected from one or more R 9 and each of X and Z is independently C(R 3 ) or N, and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C2-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NRB R C , -NR B C(O)R D , -NO2, -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 selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 optionally replaced by R 3 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R Dwherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 and each R 6 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and R 7a is hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, oxo, or -OR A and R 7b is hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and each R 8 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 9 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, halo, cyano, oxo, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and each R A are independently hydrogen, C-C alkyl, C-C haloalkyl, aryl, heteroaryl, C-C alkylene-aryl, C-C alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, -OR A or R B and R C together with the atoms to which they are attached form one or more R 10 and each RD are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 10 is independently C1-C6-alkyl or halo, and X is 0, 1, or 2.

[0464] In some embodiments, A is one or more R 1 In some embodiments, A is a monocyclic nitrogen-containing heterocyclyl. In some embodiments, A is an optionally substituted piperidinyl. In some embodiments, A is [ka] where each R 1 is independently hydrogen or C1-C6-alkyl. In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] is.

[0465] In some embodiments, A is one or more R 1In some embodiments, A is a heteroaryl optionally substituted with: In some embodiments, A is a bicyclic nitrogen-containing heteroaryl. In some embodiments, A is an optionally substituted indazolyl. In some embodiments, A is an optionally substituted imidazo[1,2-a]pyridinyl. In some embodiments, A is [ka] where each R 1 is as defined herein. In some embodiments, A is [ka] In some embodiments, A is [ka] where each R 1 is as defined herein. In some embodiments, A is [ka] In some embodiments, A is [ka] is.

[0466] In some embodiments, B is one or more R 1 In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is an optionally substituted indazolyl. In some embodiments, B is [ka] In some embodiments, B is selected from: [ka] In some embodiments, B is selected from: [ka] In some embodiments, B is [ka] is.

[0467] In some embodiments, B is one or more R 1 In some embodiments, B is a heterocyclyl optionally substituted with: In some embodiments, B is a monocyclic nitrogen-containing heterocyclyl. In some embodiments, B is an optionally substituted piperazinyl. In some embodiments, B is [ka] where R 1 is as defined herein. In some embodiments, B is [ka] In some embodiments, B is [ka] is.

[0468] In some embodiments, L 1 is absent.

[0469] In some embodiments, each of X and Z is independently N or C(R 3 In some embodiments, X can be C(R 3 ) (e.g., CH). In some embodiments, X is N. In some embodiments, Z is C(R 3) (e.g., CH). In some embodiments, Z is N. In some embodiments, each of X and Z is independently C(R 3 ) (e.g., CH). In some embodiments, each of X and Z is independently C(R 3 ) (e.g., CH).

[0470] In some embodiments, R 1 is C1-C6-alkyl. In some embodiments, R 1 In some embodiments, A is 0 or 1 R 1 In some embodiments, B is substituted with 0, 1, or 2 R 1 In some embodiments, R 7a and R 7b Each of is independently hydrogen.

[0471] In some embodiments, the compound of formula (III) is a compound of formula (III-b): [ka] 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 selected from the group consisting of one or more R 1 and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B RC , -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 selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 optionally replaced by R 3 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -S(O) x R D and each R 5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 and each R6 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and R 7b is hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and each R A are independently hydrogen, C-C alkyl, C-C haloalkyl, aryl, heteroaryl, C-C alkylene-aryl, C-C alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, -OR A or R B and R C together with the atoms to which they are attached form one or more R 10 and each R D are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 10 is independently C1-C6-alkyl or halo, and x is 0, 1, or 2.

[0472] In some embodiments, the compound of formula (III) is a compound of formula (III-c): [ka] 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 selected from the group consisting of one or more R 1 and each R 1 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -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 selected from the group consisting of one or more R 5 or two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl may be selected from one or more R 5 optionally replaced by R 3 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -S(O) x R D and each R5 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 6 and each R 6 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and R 7b is hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and each R A are independently hydrogen, C-C alkyl, C-C haloalkyl, aryl, heteroaryl, C-C alkylene-aryl, C-C alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and each R B and R C are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, -OR A or R B and R C together with the atoms to which they are attached form one or more R 10 and each RD are independently hydrogen, C-C alkyl, C-C alkenyl, C-C alkynyl, C-C heteroalkyl, C-C haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C-C alkylene-aryl, or C-C alkylene-heteroaryl; and each R 10 is independently C1-C6-alkyl or halo, and x is 0, 1, or 2.

[0473] In some embodiments, A is one or more R 1 In some embodiments, A is a monocyclic nitrogen-containing heterocyclyl. In some embodiments, A is an optionally substituted piperidinyl. In some embodiments, A is [ka] where each R 1 is independently hydrogen or C1-C6-alkyl. In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] is.

[0474] In some embodiments, A is one or more R 1In some embodiments, A is a heteroaryl optionally substituted with: In some embodiments, A is a bicyclic nitrogen-containing heteroaryl. In some embodiments, A is an optionally substituted indazolyl. In some embodiments, A is an optionally substituted imidazo[1,2-a]pyridinyl. In some embodiments, A is [ka] where each R 1 is as defined herein. In some embodiments, A is [ka] In some embodiments, A is [ka] where each R 1 is as defined herein. In some embodiments, A is [ka] In some embodiments, A is [ka] is.

[0475] In some embodiments, B is one or more R 1 In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is an optionally substituted indazolyl. In some embodiments, B is [ka] In some embodiments, B is selected from: [ka] In some embodiments, B is selected from: [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] is.

[0476] In some embodiments, Y is N, where the dashed line in the ring containing Y can be a single or double bond, valence permitting. In some embodiments, Y is N or C(R 4b In some embodiments, Y is N (e.g., N). In some embodiments, Y is C(R 4b ) (e.g., CH).

[0477] In some embodiments, L 1 is absent. In some embodiments, R 2 is absent.

[0478] In some embodiments, R 7a and R 7b Each of is independently hydrogen.

[0479] In some embodiments, R 1 is C1-C6-alkyl. In some embodiments, R 1 In some embodiments, A is 0 or 1 R 1 In some embodiments, B is substituted with 0, 1, or 2 R 1 is replaced by

[0480] In some embodiments, the compound of Formula (III) is selected from the compounds in Table 3, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. [Table 3-1] [Table 3-2] [Table 3-3] [Table 3-4] [Table 3-5] [Table 3-6] [Table 3-7] [Table 3-8] [Table 3-9] [Table 3-10] [Table 3-11] [Table 3-12] [Table 3-13] [Table 3-14]

[0481] In some embodiments, for Formula (III), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 152, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0482] In some embodiments, for Formula (III), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 153, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0483] In some embodiments, for Formula (III), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 156, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0484] In some embodiments, for Formula (III), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 157, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0485] In some embodiments, for Formula (III), A is a monocyclic heterocyclyl (e.g., 1,2,3,6-tetrahydropyridinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 158, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0486] In some embodiments, for Formula (III), A is a monocyclic heterocyclyl (e.g., N-methyl-1,2,3,6-tetrahydropyridinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 159, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0487] In some embodiments, for Formula (III), A is a bicyclic heterocyclyl (e.g., 8-azabicyclo[3.2.1]oct-2-enyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 160, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0488] In some embodiments, for Formula (III), A is a bicyclic heterocyclyl (e.g., N-methyl 8-azabicyclo[3.2.1]oct-2-enyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 161, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0489] In some embodiments, for Formula (III), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 is -N(R 8 )-(e.g., -NH-), and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III) and (III-a) is compound 162, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0490] In some embodiments, for Formula (III), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 is -N(R 8 )-(e.g., -NH-), and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7bare each independently hydrogen. In some embodiments, the compound of Formula (III) and (III-a) is compound 163, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0491] In some embodiments, for Formula (III), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 172, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0492] In some embodiments, for Formula (III), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), and L 1 and L 2 is absent, and X is C(R 3 ) (e.g., CH), Z and Y are each independently N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-b) is compound 173, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0493] In some embodiments, for Formula (III), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 174, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0494] In some embodiments, for Formula (III), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., N-methylpiperazyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 175, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0495] In some embodiments, for Formula (III), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl), B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 176, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0496] In some embodiments, for Formula (III), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 177, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0497] In some embodiments, for Formula (III), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 178, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0498] In some embodiments, for Formula (III), A is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-b) is compound 179, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0499] In some embodiments, for Formula (III), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 is -N(R 8 )-(e.g., -N(CH3)-), and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III) and (III-a) is compound 180, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0500] In some embodiments, for Formula (III), A is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 181, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0501] In some embodiments, for Formula (III), A is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 182, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0502] In some embodiments, for Formula (III), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 is -N(R 8 )-(e.g., -NH-), and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III) and (III-a) is compound 203, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0503] In some embodiments, for Formula (III), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 1 is -N(R 8 )-(e.g., -NH-), and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III) and (III-a) is compound 204, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0504] In some embodiments, for Formula (III), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3 ) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 205, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0505] In some embodiments, for Formula (III), A is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 1 and L 2 is absent, and X and Z are each independently C(R 3) (e.g., CH), Y is N, and R 2 is absent, R 7a and R 7b are each independently hydrogen. In some embodiments, the compound of Formula (III), (III-a), and (III-c) is compound 206, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0506] In some embodiments, for Formula (III), A is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl), and L 1 and L 2 is absent, and ...

Claims

(i) A compound of formula (I): 【Chemical 1】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof (In the formula, A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R １ optionally replaced by L １ and L ２ Each of the is independently absent, C １ -C ６ - alkylene, C １ -C ６ -heteroalkylene, -O-, -C(O)-, -N(R ４ ) -, -N(R ４ )C(O)-, or -C(O)N(R ４ )—, where each alkylene and heteroalkylene is selected from one or more R ７ optionally replaced by Y is N, C(R ６ａ ), or C(R ６ａ ) (R ６ｂ ) wherein the dashed line in the ring containing Y can be a single or double bond, valence permitting; Each R １ are 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 ２ -C ６ Alkenylene-aryl, heteroaryl, 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 selected from one or more R ５ or Two R's １ The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R ５ optionally replaced by Each R ２ are 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, halo, cyano, cycloalkyl, heterocyclyl, -OR Ａ , -NR Ｂ R Ｃ , -C(O)R Ｄ , -C(O)OR Ｄ , —C(O)NR Ｂ R Ｃ , -NR Ｂ C(O)R Ｄ , or -S(O) ｘ R Ｄ and 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, -OR Ａ , -NR Ｂ R Ｃ , -C(O)R Ｄ , -C(O)OR Ｄ , C(O)NR Ｂ R Ｃ , -NR Ｂ C(O)R Ｄ , or -S(O) ｘ R Ｄ and R ４ is hydrogen, C １ -C ６ - alkyl, or C １ -C ６ -haloalkyl, Each R ５ are independently 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, oxo, 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 wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R ７ optionally replaced by R ６ａ and R ６ｂ are independently hydrogen, C １ -C ６ -Alkyl, C １ -C ６ -heteroalkyl, C １ -C ６ -haloalkyl or halo, Each R ７ are independently １ -C ６ -Alkyl, C １ -C ６ -heteroalkyl, C １ -C ６ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR Ａ and Each R Ａ are 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, C １ -C ６ Alkylene-heteroaryl, —C(O)R Ｄ , or -S(O) ｘ R Ｄ wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R ９ optionally replaced by Each R Ｂ and R Ｃ are 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, C １ -C ６ alkylene-heteroaryl, -OR Ａ , -S(O) ｘ R Ｄ or R Ｂ and R Ｃ together with the atoms to which they are attached, form one or more R ９ forming a 3- to 7-membered heterocyclyl ring optionally substituted with Each R Ｄ are 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, and each R ９ are independently １ -C ６ -alkyl, halo, or -OR Ａ１ and Each R Ａ１ is hydrogen or C １ -C ６ - alkyl, Each R ９ and R １０ are independently １ -C ６ -alkyl, halo, or -OR Ａ１ and m is 0, 1, 2, or 3; n is 0, 1, or 2; x is 0, 1, or 2. or (ii) A compound of formula (II): 【Chemical 32】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof (In the formula, A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R 1 ; each of L 1 and L 2 is independently absent, 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 )—, wherein each alkylene and heteroalkylene is optionally substituted with one or more R 9 ; each of W, X, and Z is independently C(R 3 ) or N; Y is N, N(R 4a ), C(R 4b ), or C(R 4b )(R 4c ), where the dashed line in the ring containing Y may be a single or double bond, valence permitting; 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 5 ; or two R 1 groups together with the atoms to which they are attached form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R 5 ; R 2 is absent, hydrogen or C 1 -C 6 -alkyl; 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, -OR A , -NR B R C , -C(O)R D , -C(O)OR D or -S(O) x R D , R 4a is hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -heteroalkyl, or C 1 -C 6 -haloalkyl; each of R 4b and R 4c is independently hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -heteroalkyl, C 1 -C 6 -haloalkyl, halo, or —OR A ; each R 5 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, oxo, 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 , wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R 6 ; each R 6 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 8 is independently hydrogen, C 1 -C 6 -alkyl, or C 1 -C 6 -haloalkyl; each R 9 is independently C 1 -C 6 -alkyl, C 1 -C 6 -heteroalkyl, C 1 -C 6 -haloalkyl, cycloalkyl, halo, cyano, oxo, —OR A , —NR B R C , —C(O)R D , or —C(O)OR D ; each R A 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, C 1 -C 6 alkylene-heteroaryl, -C(O)R D , or -S(O) xR D , wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R 9 ; each R B and R C independently is 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, C 1 -C 6 alkylene-heteroaryl, -OR A , -S(O) x R D , or R B and R C together with the atoms to which they are attached form a 3- to 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 10 is independently C 1 -C 6 -alkyl or halo; x is 0, 1, or 2. or (iii) A compound of formula (III): 【Chemistry 52】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof (In the formula, A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R 1 ; each of L 1 and L 2 is independently absent, 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 )—, wherein each alkylene and heteroalkylene is optionally substituted with one or more R 9 ; Each of X and Z is independently C(R 3 ) or N; Y is N, C, or C(R 4b ), where the dashed line in the ring containing Y may be a single or double bond, valence permitting; 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 5 ; or two R 1 groups together with the atoms to which they are attached form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R 5 ; R 2 is absent, hydrogen or C 1 -C 6 -alkyl; R 3 is 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, halo, cyano, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -S(O) x R D , R 4b is hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -heteroalkyl, or C 1 -C 6 -haloalkyl; each R 5 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, oxo, 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 , wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R 6 ; each R 6 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 ; R 7a is hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -heteroalkyl, C 1 -C 6 -haloalkyl, halo, cyano, oxo, or —OR A ; R 7b is hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -heteroalkyl, C 1 -C 6 -haloalkyl, halo, cyano, or —OR A ; each R 8 is independently hydrogen, C 1 -C 6 -alkyl, or C 1 -C 6 -haloalkyl; each R 9 is independently C 1 -C 6 -alkyl, C 1 -C 6 -heteroalkyl, C 1 -C 6 -haloalkyl, cycloalkyl, halo, cyano, oxo, —OR A , —NR B R C , —C(O)R D , or —C(O)OR D ; 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 A , or R B and R C together with the atoms to which they are attached form a 3- to 7-membered heterocyclyl ring optionally substituted with one or more R 10 ; 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 10 is independently C 1 -C 6 -alkyl or halo; x is 0, 1, or 2. or (iv) A compound of formula (IV): 【Chemical 72】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof (In the formula, 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 X are each independently C(R 3 ) or N, where one of W and X is independently N; each of L 1 and L 2 is independently absent, C 1 -C 6 -alkylene, C 1 -C 6 -heteroalkylene, —O—, —C(O)—, —N(R 4 )—, —N(R 4 )C(O)—, or —C(O)N(R 4 )—, wherein each alkylene and heteroalkylene is optionally substituted with one or more 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 2 -C 6 alkenylene-aryl, heteroaryl, 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 5 ; or two R 1 groups together with the atoms to which they are attached form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R 5 ; R 2a , R 2b and R 2c are each 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, halo, cyano, cycloalkyl, heterocyclyl, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -C(O)NR B R C or -S(O) x R D ; R 3 is 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, halo, cyano, cycloalkyl, heterocyclyl, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -C(O)NR B R C or -S(O) x R D , R 4 is hydrogen, C 1 -C 6 -alkyl or C 1 -C 6 -haloalkyl; each R 5 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, oxo, 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 , wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R 7 ; each R 6 and R 7 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 A is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 haloalkyl, aryl, heteroaryl, C 1 -C 6 alkylene-aryl, C 1 -C 6 alkylene-heteroaryl, cycloalkyl, heterocyclyl, —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, C 1 -C 6 haloalkyl, aryl, heteroaryl, C 1 -C 6 alkylene-aryl, C 1 -C 6 alkylene-heteroaryl, cycloalkyl, heterocyclyl, -OR A , -S(O) x R D ; or R B and R C together with the atoms to which they are attached form a 3- to 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 9 is independently C 1 -C 6 -alkyl or halo; x is 0, 1, or 2. or (v) A compound of formula (V): 【Chemistry 100】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof (In the formula, A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R 1 ; W, X, and Y are each independently C(R 3 ) or N, where at least one of W, X, and Y is independently N; each of L 1 and L 2 is independently absent, C 1 -C 6 -alkylene, C 1 -C 6 -heteroalkylene, —O—, —C(O)—, —N(R 4 )—, —N(R 4 )C(O)—, or —C(O)N(R 4 )—, wherein each alkylene and heteroalkylene is optionally substituted with one or more 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 2 -C 6 alkenylene-aryl, heteroaryl, 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 5 ; or two R 1 groups together with the atoms to which they are attached form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R 5 ; R 2 is 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, halo, cyano, cycloalkyl, heterocyclyl, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -C(O)NR B R C or -S(O) x R D , R 3 is 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, halo, cyano, cycloalkyl, heterocyclyl, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -C(O)NR B R C or -S(O) x R D , R 4 is hydrogen, C 1 -C 6 -alkyl or C 1 -C 6 -haloalkyl; each R 5 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, oxo, 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 , wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R 7 ; each R 6 and R 7 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 A is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 haloalkyl, aryl, heteroaryl, C 1 -C 6 alkylene-aryl, C 1 -C 6 alkylene-heteroaryl, cycloalkyl, heterocyclyl, —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, C 1 -C 6 haloalkyl, aryl, heteroaryl, C 1 -C 6 alkylene-aryl, C 1 -C 6 alkylene-heteroaryl, cycloalkyl, heterocyclyl, -OR A , -S(O) x R D ; or R B and R C together with the atoms to which they are attached form a 3- to 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 9 is independently C 1 -C 6 -alkyl or halo; x is 0, 1, or 2. A compound selected from one of:

2. The compound of claim 1, wherein in formula (I), (II), (III), (IV), or (V), one of A and B is independently a nitrogen-containing heterocyclyl, an oxygen-containing heterocyclyl, or a nitrogen-containing heteroaryl.

3. In formula (I), (II), (III), (IV), or (V), one of A and B is 【Chemistry 2】 wherein R １ The compound of claim 1, wherein:

4. In formula (I), (II), (III), (IV), or (V), one of A and B is 【Chemistry 13】 wherein R １ The compound of claim 1, wherein:

5. In formula (I), (i) L １ and L ２ Each of these is, independently, absent; (ii) Y is C(R 6a ) (e.g., CH) or N; (iii) R 2 is hydrogen or alkyl (e.g., CH 3 ); (iv) n is 1 or 2; and / or (v) m is 0 or 1; The compound of claim 1.

6. The compound of formula (I) (i) A compound of formula (Ia): 【Chemistry 18】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, R ２ , R ３ and its subvariables are as defined in claim 1; or (ii) Compound of formula (I-b): 【Chemistry 19】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, R 2 , R 3 , and subvariables thereof are as defined in claim 1. The compound of claim 1.

7. In formula (II), (i) L １ and L ２ Each of these is, independently, absent; (ii) W is C(R 3 ) (e.g., CH); (iii) X is C(R 3 ) (e.g., CH); (iv) Z is C(R 3 ) (e.g., CH); and / or (v) Y is N(R 4a ) or C(R 4b ), (e.g., NH); The compound of claim 1.

8. The compound of formula (II) (i) A compound of formula (II-a): 【Chemistry 48】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L １ , W, X, Z, R ４ａ and its subvariables are as defined in claim 1; (ii) Compound of formula (II-b): 【Chemistry 49】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, Y, R 2 and subvariables thereof are as defined in claim 1; (iii) Compound of formula (II-c): 【Chemistry 50】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, Y, R 4a and subvariables thereof are as defined in claim 1; or (iv) Compound of formula (II-d): 【Chemistry 51】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , R 4a , and subvariables thereof are as defined in claim 1; The compound of claim 1.

9. In formula (III), (i) L １ and L ２ Each of these is, independently, absent; (ii) X is C(R 3 ) (e.g., CH); (iii) Z is C(R 3 ) (e.g., CH); and / or (iv) Y is N; The compound of claim 1.

10. The compound of formula (III) (i) A compound of formula (III-a): 【Chemical Formula 67】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, X, Z, R ７ｂ and its subvariables are as defined in claim 1; (ii) A compound of formula (III-b): 【Chemistry 68】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, R 3 , R 7b and subvariables thereof are as defined in claim 1; or (iii) Compound of formula (III-c): 【Chemical Formula 69】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, R 3 , R 7b , and subvariables thereof are as defined in claim 1; The compound of claim 1.

11. In formula (IV), (i) L １ and L ２ Each of these is, independently, absent; (ii)(a) W is C(R 3 ) (e.g., CH); or (b) W is N; (iii) X is N; and / or (iv) (a) each of W and X is N; or (b) W is C(R 3 ) (e.g., CH) and X is N; and / or (v) each of R 2a , R 2b , and R 2c is independently hydrogen or alkyl (e.g., CH 3 ); The compound of claim 1.

12. In the formula (IV), the compound of the formula (IV) is (i) Compound of formula (IV-a): 【Chemistry 94】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L １ , L ２ , R ２ａ , R ２ｂ , R ２ｃ and its subvariables are as defined in claim 1; (ii) Compound of formula (IV-d): 【Chemistry 97】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, R 2b , R 3 , and subvariables thereof are as defined in claim 1; or (iii) Compound of formula (IV-e): 【Chemistry 98】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , R 2a , R 2b , R 2c , R 3 , and subvariables thereof are as defined in claim 1. The compound of claim 1.

13. In formula (V), (i) L １ and L ２ Each of these is absent; (ii)(a) W is C(R 3 ) (e.g., CH); or (b) W is N; and / or (iii) X is C(R 3 ) (e.g., CH); and / or (iv) Y is C(R 3 ) (e.g., CH); The compound of claim 1.

14. The compound of formula (V) (i) A compound of formula (Va): 【Chemical 122】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L １ , L ２ , R ２ , R ３ and its subvariables are as defined in claim 1; or (ii) A compound of formula (V-e): 【126】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , R 2a , R 2b , R 2c , R 3 , and subvariables thereof are as defined in claim 1. The compound of claim 1.

15. 2. The compound of claim 1, wherein the compound is a compound provided in one of Tables 1, 2, 3, 4, or 5, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. (i) A compound of formula (VI): 【128】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof (In the formula, A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R １ optionally replaced by W and X are each independently C(R ３ ) or N, L １ and L ２ Each of the is independently absent, C １ -C ６ - alkylene, C １ -C ６ -heteroalkylene, -O-, -C(O)-, -N(R ４ ) -, -N(R ４ )C(O)-, or -C(O)N(R ４ )—, where each alkylene and heteroalkylene is selected from one or more R ６ optionally replaced by Each R １ are 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 ２ -C ６ Alkenylene-aryl, heteroaryl, 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 selected from one or more R ５ or Two R's １ The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R ５ optionally replaced by R ２ａ , R ２ｂ , and R ２ｃ are each 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, halo, cyano, cycloalkyl, heterocyclyl, -OR Ａ , -NR Ｂ R Ｃ , -C(O)R Ｄ , -C(O)OR Ｄ , —C(O)NR Ｂ R Ｃ , or -S(O) ｘ R Ｄ and R ３ is 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, halo, cyano, cycloalkyl, heterocyclyl, -OR Ａ , -NR Ｂ R Ｃ , -C(O)R Ｄ , -C(O)OR Ｄ , —C(O)NR Ｂ R Ｃ , or -S(O) ｘ R Ｄ and R ４ is hydrogen, C １ -C ６ - alkyl, or C １ -C ６ -haloalkyl, Each R ５ are independently 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, oxo, 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 wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R ７ optionally replaced by Each R ６ and R ７ are independently １ -C ６ -Alkyl, C １ -C ６ -heteroalkyl, C １ -C ６ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR Ａ and Each R Ａ are independently hydrogen, C １ -C ６ Alkyl, C １ -C ６ Heteroalkyl, C １ -C ６ Haloalkyl, aryl, heteroaryl, C １ -C ６ Alkylene-aryl, C １ -C ６ Alkylene-heteroaryl, cycloalkyl, heterocyclyl, —C(O)R Ｄ , or -S(O) ｘ R Ｄ and Each R Ｂ and R Ｃ are independently hydrogen, C １ -C ６ Alkyl, C １ -C ６ Heteroalkyl, C １ -C ６ Haloalkyl, aryl, heteroaryl, C １ -C ６ Alkylene-aryl, C １ -C ６ Alkylene-heteroaryl, cycloalkyl, heterocyclyl, -OR Ａ , -S(O) ｘ R Ｄ or R Ｂ and R Ｃ together with the atoms to which they are attached, form one or more R ９ forming a 3- to 7-membered heterocyclyl ring optionally substituted with Each R Ｄ are 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 ９ are independently １ -C ６ - alkyl or halo, x is 0, 1, or 2. or (ii) A compound of formula (VII): 【Chemistry 156】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof (In the formula, A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R 1 ; each of L 1 and L 2 is independently absent, C 1 -C 6 -alkylene, C 1 -C 6 -heteroalkylene, —O—, —C(O)—, —N(R 4 )—, —N(R 4 )C(O)—, or —C(O)N(R 4 )—, wherein each alkylene and heteroalkylene is optionally substituted with one or more 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 2 -C 6 alkenylene-aryl, heteroaryl, 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 5 ; or two R 1 groups together with the atoms to which they are attached form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R 5 ; R 2a , R 2b and R 2c are each 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, halo, cyano, cycloalkyl, heterocyclyl, -OR A , -NR B R C , -C(O)R D , -C(O)OR D , -C(O)NR B R C or -S(O) x R D ; R 4 is hydrogen, C 1 -C 6 -alkyl or C 1 -C 6 -haloalkyl; each R 5 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, oxo, 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 , wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R 7 ; each R 6 and R 7 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 A is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 haloalkyl, aryl, heteroaryl, C 1 -C 6 alkylene-aryl, C 1 -C 6 alkylene-heteroaryl, cycloalkyl, heterocyclyl, —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, C 1 -C 6 haloalkyl, aryl, heteroaryl, C 1 -C 6 alkylene-aryl, C 1 -C 6 alkylene-heteroaryl, cycloalkyl, heterocyclyl, -OR A , -S(O) x R D ; or R B and R C together with the atoms to which they are attached form a 3- to 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 9 is independently C 1 -C 6 -alkyl or halo; x is 0, 1, or 2. A compound selected from one of:

17. The compound of claim 16, wherein in formula (VI) or (VII), one of A and B is independently a nitrogen-containing heterocyclyl or a nitrogen-containing heteroaryl.

18. In formula (VI), (i) One of A and B is 【129】 wherein R １ is as defined in claim 16; and / or (ii) one of A and B is 【Chemistry 139】 wherein R 1 is as defined in claim 16; 17. The compound of claim 16.

19. In formula (VI), (i) L １ and L ２ Each of these is, independently, absent; (ii)(a) each of W and X is N; (b) W is N and X is C(R 3 ) (e.g., CH); (c) W is C(R 3 ) (e.g., CH) and X is N; or (d) W is C(R 3 ) (e.g., CH) and X is C(R 3 ) (e.g., CH); and / or (iii) each of R 2a , R 2b , and R 2c is independently hydrogen or alkyl (e.g., CH 3 ); 17. The compound of claim 16.

20. The compound of formula (VI) (i) A compound of formula (VI-a): 【148】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L １ , L ２ , R ２ａ , R ２ｂ , R ２ｃ and its subvariables are as defined in claim 16; (ii) Compound of formula (VI-b): 【149】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, R 2c , and subvariables thereof are as defined in claim 16; (iii) Compound of formula (VI-c): 【Chemistry 150】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , R 2a , R 2b , R 2c , R 3 , and subvariables thereof are as defined in claim 16; (iv) Compound of formula (VI-d): 【Chemistry 151】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, R 3 , and subvariables thereof are as defined in claim 16; (v) Compound of formula (VI-e): 【Chemistry 152】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , R 2a , R 2b , R 2c , R 3 , and subvariables thereof are as defined in claim 16; (vi) Compound of formula (VI-f): 【Chemistry 153】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, R 3 , and subvariables thereof are as defined in claim 16; (vii) Compound of formula (VI-g): 【Chemistry 154】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , R 2a , R 2b , R 2c , R 3 , and subvariables thereof are as defined in claim 16; or (viii) Compound of formula (VI-h): 【Chemistry 155】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, R 3 , and subvariables thereof are as defined in claim 16.

17. The compound of claim 16.

21. In formula (VII), A is a nitrogen-containing heteroaryl and B is a nitrogen-containing heterocyclyl, wherein each heterocyclyl and heteroaryl is selected from one or more R １ 17. The compound of claim 16, optionally substituted with

22. In formula (VII), (i) One of A and B is 【Chemistry 157】 wherein R １ is as defined in claim 16; and / or (ii) one of A and B is 【Chemistry 165】 wherein R 1 is as defined in claim 16; 17. The compound of claim 16.

23. In formula (VII), (i) L １ and L ２ are independently absent; and / or (ii) each of R 2a , R 2b , and R 2c is independently selected from hydrogen or alkyl (e.g., CH 3 ); 17. The compound of claim 16.

24. In the formula (VII), the compound of formula (VII) is (i) A compound of formula (VII-a): 【176】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L １ , L ２ and its subvariables are as defined in claim 16; or (ii) Compound of formula (VII-ab): 【Chemical 177】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, and subvariables thereof are as defined in claim 16.

17. The compound of claim 16.

25. 17. The compound of claim 16, wherein the compound of formula (VI) or (VII) is a compound provided in Table 6 or 7, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

26. 1. A composition for use in treating a proliferative disorder in a subject, comprising administering to said subject a compound of formula (XIII), wherein said compound of formula (IX) is 【Chemical 229】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof (In the formula, A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R １ optionally replaced by L １ and L ２ Each of the is independently absent, 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 )—, where each alkylene and heteroalkylene is selected from one or more R ９ optionally replaced by Each of W, X, and Z is independently C(R ３ ) or N, Y is N, C, or C(R ４ｂ ) wherein the dashed line in the ring containing Y can be a single or double bond, valence permitting; Each R １ are 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 ２ -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 selected from one or more R ５ or Two R's １ The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R ５ optionally replaced by R ２ is absent, hydrogen, or C １ -C ６ - alkyl, R ３ is 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, halo, cyano, -OR Ａ , -NR Ｂ R Ｃ , -C(O)R Ｄ , or —C(O)OR Ｄ and R ４ｂ is hydrogen, C １ -C ６ -Alkyl, C １ -C ６ -heteroalkyl, or C １ -C ６ -haloalkyl, Each R ５ are independently 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, oxo, 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 wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R ６ optionally replaced by Each R ６ are independently １ -C ６ -Alkyl, C １ -C ６ -heteroalkyl, C １ -C ６ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR Ａ and R ７ is hydrogen, C １ -C ６ -Alkyl, C １ -C ６ -heteroalkyl, C １ -C ６ -haloalkyl, halo, cyano, oxo, or -OR Ａ and Each R ８ are independently hydrogen, C １ -C ６ - alkyl, or C １ -C ６ -haloalkyl, Each R ９ are independently １ -C ６ -Alkyl, C １ -C ６ -heteroalkyl, C １ -C ６ -haloalkyl, cycloalkyl, halo, cyano, oxo, -OR Ａ , -NR Ｂ R Ｃ , -C(O)R Ｄ , or —C(O)OR Ｄ and Each R Ａ are 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 and Each R Ｂ and R Ｃ are independently hydrogen, C １ -C ６ Alkyl, C １ -C ６ Heteroalkyl, cycloalkyl, heterocyclyl, -OR Ａ or R Ｂ and R Ｃ together with the atoms to which they are attached, form one or more R １０ forming a 3- to 7-membered heterocyclyl ring optionally substituted with Each R Ｄ are 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 １０ are independently １ -C ６ - alkyl or halo, and x is 0, 1, or 2.

27. 27. The composition for use of claim 26, wherein the compound is formulated as a pharmaceutical composition.

28. 27. The composition for use according to claim 26, wherein the proliferative disease is cancer.

29. 29. The composition for use of claim 28, wherein the cancer is selected from adenoid cystic carcinoma, colon cancer, leukemia, lung cancer, prostate cancer, or ovarian cancer.

30. 1. A composition for use in treating a proliferative disorder in a subject, comprising administering to said subject a compound of formula (IX), wherein said compound of formula (IX) is 【Chemistry 230】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof (In the formula, A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R １ optionally replaced by L １ and L ２ Each of these is absent, 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 )—, where each alkylene and heteroalkylene is selected from one or more R ９ optionally replaced by Each of X and Z is independently C(R ３ ) or N, Y is N, N(R ４ａ ), C(R ４ｂ ), or C(R ４ｂ ) (R ４ｃ ) wherein the dashed line in the ring containing Y can be a single or double bond, valence permitting; Each R １ are 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 ２ -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 selected from one or more R ５ or Two R's １ The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R ５ optionally replaced by R ２ is absent, hydrogen, or C １ -C ６ - alkyl, R ３ is 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, halo, cyano, -OR Ａ , -NR Ｂ R Ｃ , -C(O)R Ｄ , or —C(O)OR Ｄ and R ４ａ is hydrogen, C １ -C ６ -Alkyl, C １ -C ６ -heteroalkyl, or C １ -C ６ -haloalkyl, R ４ｂ and R ４ｃ each independently represents hydrogen, C １ -C ６ -Alkyl, C １ -C ６ -heteroalkyl, C １ -C ６ -haloalkyl, halo, or -OR Ａ and Each R ５ are independently 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, oxo, 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 wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R ６ optionally replaced by Each R ６ are independently １ -C ６ -Alkyl, C １ -C ６ -heteroalkyl, C １ -C ６ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR Ａ and R ７ｂ is hydrogen, C １ -C ６ -Alkyl, C １ -C ６ -heteroalkyl, C １ -C ６ -haloalkyl, halo, cyano, or -OR Ａ and Each R ８ are independently hydrogen, C １ -C ６ - alkyl, or C １ -C ６ -haloalkyl, Each R ９ are independently １ -C ６ -Alkyl, C １ -C ６ -heteroalkyl, C １ -C ６ -haloalkyl, cycloalkyl, halo, cyano, oxo, -OR Ａ , -NR Ｂ R Ｃ , -C(O)R Ｄ , or —C(O)OR Ｄ and Each R Ａ are 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 and Each R Ｂ and R Ｃ are independently hydrogen, C １ -C ６ Alkyl, C １ -C ６ Heteroalkyl, cycloalkyl, heterocyclyl, -OR Ａ or R Ｂ and R Ｃ together with the atoms to which they are attached, form one or more R １０ forming a 3- to 7-membered heterocyclyl ring optionally substituted with Each R Ｄ are 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 １０ are independently １ -C ６ - alkyl or halo, and x is 0, 1, or 2.

31. 31. The composition for use of claim 30, wherein the compound is formulated as a pharmaceutical composition.

32. 31. The composition for use according to claim 30, wherein the proliferative disease is cancer.

33. 33. The composition for use of claim 32, wherein the cancer is selected from adenoid cystic carcinoma, colon cancer, leukemia, lung cancer, prostate cancer, or ovarian cancer.

34. A pharmaceutical composition comprising the compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

35. The compound of claim 34, (i) modifying a target nucleic acid (e.g., RNA, e.g., pre-mRNA); (ii) binds to a target nucleic acid (e.g., RNA, e.g., pre-mRNA); or (iii) stabilizes a target nucleic acid (e.g., RNA, e.g., pre-mRNA); The compound of claim 1.

36. A method of forming a complex comprising a spliceosome component (e.g., a major spliceosome component or a minor spliceosome component), a nucleic acid (e.g., DNA, RNA, e.g., pre-mRNA), and a compound of claim 1, comprising: contacting the nucleic acid (e.g., DNA, RNA, e.g., pre-mRNA) with a compound of formula (I), (II), (III), (IV), (V), (VI), or (VII).

37. A composition for treating a disease or disorder in a subject, comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, or a composition thereof.

38. The disease or disorder: (i) a proliferative disease (e.g., cancer, benign neoplasm, or inflammatory disease); (ii) a nervous system disease or disorder, an autoimmune disease or disorder, an 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 kidney disease or disorder, or an infectious disease; (iii) a nervous system disease or disorder; and / or (iv) Huntington's disease 38. The composition of claim 37, comprising:

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