Compounds and methods for modulating splicing

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 / 238,691 filed August 30, 2021, U.S. Patent Application No. 63 / 238,694 filed August 30, 2021, U.S. Patent Application No. 63 / 282,906 filed November 24, 2021, U.S. Patent Application No. 63 / 283,132 filed November 24, 2021, U.S. Patent Application No. 63 / 393,205 filed July 28, 2022, and U.S. Patent Application No. 63 / 393,206 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 using them. In one embodiment, the compounds described herein are compounds of Formula (I) or (II) (e.g., compounds of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m)) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers thereof. Accordingly, the present disclosure provides compounds of the present invention (e.g., compounds of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m), and pharmaceutically acceptable salts, solvates, hydrates, and the like thereof). Methods are provided for using the compounds described herein (e.g., tautomers, tautomers, stereoisomers, and compositions thereof) to target, and in embodiments bind to, or form complexes 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, and U6atac snRNPs), or combinations thereof. In another aspect, the compounds described herein can be used to alter the composition or make-up of nucleic acids (e.g., pre-mRNA or mRNA (e.g., mRNA resulting from pre-mRNA and pre-mRNA), e.g., by increasing or decreasing splicing at splice sites. 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 (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m), 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 a benign neoplasm). In some embodiments, the compounds described herein (e.g., compounds of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m), 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 (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, and 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.

[0005] In another 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, X, Y, Z, L 1 , L 2 , R 2 , m, and their subvariables are 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, M, P, W, U, X, Y, Z, L 1 , L 2 , and its subvariables are as described herein.

[0007] In another aspect, the present invention provides a pharmaceutical composition comprising a compound of Formula (I) or (II) (e.g., a compound of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), or (Ii)), 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) or (II) (e.g., a compound of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m)), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0008] In another aspect, the disclosure provides a method for modulating splicing, e.g., splicing of a nucleic acid (e.g., DNA or RNA, e.g., pre-mRNA), with a compound of Formula (I) or (II) (e.g., a compound of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m)) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another aspect, the present disclosure provides compositions for use in modulating splicing, e.g., splicing of nucleic acids (e.g., DNA or RNA, e.g., pre-mRNA), with a compound of Formula (I) or (II) (e.g., a compound of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m)) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. Modulation of splicing can include affecting any step involved in splicing and can include events upstream or downstream of the splicing event. For example, in some embodiments, a compound of Formula (I) or (II) 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 a pre-mRNA or a component of the splicing machinery, such as the U1 snRNP. In some embodiments, a compound of Formula (I) or (II) 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) or (II) increases or decreases splicing at a splice site on a target nucleic acid (e.g., an RNA, e.g., a precursor RNA, e.g., a pre-mRNA) by about 0.5% or more (e.g., about 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 90%, 95% or more) relative to a reference (e.g., in the absence of a compound of Formula (I) or (II), e.g., a healthy or diseased cell or tissue). In some embodiments, the presence of a compound of Formula (I) or (II) 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) or (II)).

[0009] 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) or (II) (e.g., a compound of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m)) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or a 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 present disclosure provides methods for treating and / or preventing non-proliferative diseases, disorders, or conditions. In yet other embodiments, the present disclosure provides methods for treating and / or preventing nervous system diseases or disorders, autoimmune diseases or disorders, immunodeficiency diseases or disorders, lysosomal storage diseases or disorders, cardiovascular diseases or disorders, metabolic diseases or disorders, respiratory diseases or disorders, renal diseases or disorders, or infectious diseases.

[0010] 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) or (II) (e.g., a compound of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m)) 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) or (II) (e.g., a compound of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m)) 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) or (II) (e.g., a compound of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m)) 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) or (II) to a biological sample, cell, or subject includes inhibiting cell growth or inducing cell death.

[0011] 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) or (II) (e.g., a compound of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m)) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or a 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 present disclosure provides methods for treating and / or preventing non-proliferative diseases, disorders, or conditions. In yet other embodiments, the present disclosure provides methods for treating and / or preventing nervous system diseases or disorders, autoimmune diseases or disorders, immunodeficiency diseases or disorders, lysosomal storage diseases or disorders, cardiovascular diseases or disorders, metabolic diseases or disorders, respiratory diseases or disorders, renal diseases or disorders, or infectious diseases.

[0012] In another aspect, the disclosure provides a composition for use in 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) or (II) (e.g., a compound of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m)) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another aspect, the disclosure provides a composition for use in 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) or (II) (e.g., a compound of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m)) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another aspect, the present disclosure provides a composition for use in modifying a target protein isoform in a biological sample or a subject with a compound of Formula (I) or (II) (e.g., a compound of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m)) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. Another aspect of the present disclosure relates to a composition for use in inhibiting the activity of a target protein in a biological sample or a subject. In some embodiments, administration of a compound of Formula (I) or (II) to a biological sample, cell, or subject includes inhibiting cell growth or inducing cell death.

[0013] In another aspect, the disclosure features a kit including a container having a compound of Formula (I) or (II) (e.g., a compound of Formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), or (II-m)), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or pharmaceutical composition thereof. In certain embodiments, the kits described herein further include instructions for administering a compound of Formula (I) or (II), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or pharmaceutical composition thereof.

[0014] 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 WO2021 / 174165, a compound other than a target nucleic acid (e.g., DNA, RNA, e.g., pre-mRNA), or a target protein. 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 WO2021 / 174165, each of which is incorporated by reference in its entirety.

[0015] 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

[0016] 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.

[0017] 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.

[0018] 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.

[0019] 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.

[0020] 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.

[0021] 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.

[0022] 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.

[0023] 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").

[0024] 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").

[0025] 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.

[0026] As used herein, "heteroaryl" refers to a radical of a 5- to 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 contributed to the aromatic ring system ("5- to 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").

[0027] 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.

[0028] 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.

[0029] 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 8 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.

[0030] 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).

[0031] 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)-.

[0032] 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.

[0033] As used herein, the term "halogen" or "halo" refers to fluorine, chlorine, bromine or iodine.

[0034] As used herein, the term "hydroxy" refers to --OH.

[0035] As used herein, the term "nitro" refers to a substituent having two oxygen atoms bonded to a nitrogen atom, eg, --NO.sub.2.

[0036] 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.

[0037] 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. In one embodiment, the term "nucleic acid" includes a gene, cDNA, pre-mRNA, or mRNA, where the nucleic acid molecule is 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.

[0038] As used herein, "oxo" refers to carbonyl, i.e., --C(O)--.

[0039] As used herein with respect to compounds of formula (I) or (II), the symbol " [ka] " refers to a point of attachment to another moiety or functional group within a compound.

[0040] 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 which satisfy the valence of the heteroatom and result in the formation of a stable moiety.

[0041] 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.

[0042] 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").

[0043] 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.

[0044] 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.

[0045] 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.

[0046] 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.

[0047] 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.

[0048] In certain embodiments, the active ingredient can be formulated with few or no excipients or carriers.

[0049] 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.

[0050] 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.

[0051] 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.

[0052] The term "solvate" refers to a form of a compound associated with a solvent, usually through a solvolysis reaction. This physical association may involve hydrogen bonding. Conventional solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, etc. Compounds of formula (I) or (II) may be prepared, for example, in crystalline form and solvated. Suitable solvates include pharmaceutically acceptable solvates, further including both stoichiometric and non-stoichiometric solvates. In certain cases, solvates 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.

[0053] 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)).

[0054] 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.

[0055] Other definitions The following definitions are of more general terms used throughout this disclosure.

[0056] 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.

[0057] 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.

[0058] 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.

[0059] The terms "administer," "administering," or "administration," as used herein, refer to implantation, absorption, ingestion, injection, inhalation, or otherwise introduction of the pharmaceutical composition.

[0060] As used herein, the terms "condition," "disease," and "disorder" are used interchangeably.

[0061] An "effective amount" of a compound of formula (I) or (II) refers to an amount sufficient to induce a desired biological response, i.e., to treat a condition. As will be understood by those skilled in the art, the effective amount of a compound of formula (I) or (II) 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 therapeutic and prophylactic treatments. For example, in the treatment of cancer, an effective amount of a compound of the present invention can reduce tumor tissue burden or stop tumor growth or spread.

[0062] A "therapeutically effective amount" of a compound of Formula (I) or (II) is an amount sufficient to provide a therapeutic benefit in the treatment of a condition or to delay or minimize one or more symptoms associated with the condition. In some embodiments, a therapeutically effective amount is an amount sufficient to provide a therapeutic benefit in the treatment of a condition or to minimize one or more symptoms associated with the condition. A therapeutically effective amount of a compound 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.

[0063] 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.

[0064] 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) or (II)), 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.

[0065] "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.

[0066] 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 of the symptoms, manifestations, or underlying causes of a disease, disorder, or condition (e.g., those described herein), e.g., by administering a therapy, e.g., a compound described herein (e.g., a compound of Formula (I) or (II)). In one embodiment, treating includes a reduction, amelioration, alleviation, delay in onset, or inhibition of progression of the symptoms of a disease, disorder, or condition. In one embodiment, treating includes a reduction, amelioration, alleviation, delay in onset, or inhibition of progression of the manifestations of a disease, disorder, or condition. In one embodiment, treating includes a reduction, amelioration, alleviation, reduction, or delay in onset of the underlying causes 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 performed 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 resolved, e.g., to delay or prevent recurrence. Treatment may also be continued after symptoms have resolved, e.g., to delay or prevent recurrence. In some embodiments, treatment includes prevention, and in other embodiments, it does not include prevention.

[0067] "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.

[0068] "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.

[0069] compound The present disclosure provides a compound of formula (I): [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 X, Y, and Z are each independently C(R 3a ), C(R 3a )(R 3b ), N, N(R 3c), or O, where at least one of X, Y, and Z is N, N(R 3c ), or O, and the bonds in the ring containing X, Y, and Z may be single or double bonds, valence permitting; 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 5 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 , -SR E , 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 6 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 is selected from the group consisting of one or more R 6 and each R 2are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and R 3a and R 3b are each independently hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D or R 3a and R 3b together with the carbon atom to which they are attached form an oxo group, and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, C1-C6 alkylene-cycloalkyl, heterocyclyl, C1-C6 alkylene-heterocyclyl, aryl, C1-C6 alkylene-aryl, heteroaryl, C1-C6 alkylene-heteroaryl, or -C(O)R D and each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 8 and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , 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 11 and each R 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 8 is C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , or -S(O) x R D and each R 11 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R Aare 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 R B and R C each independently represents hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, or -OR A or R B and R C together with the atoms to which they are attached form one or more R 7 and each R D and R E 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 A1 is hydrogen or C1-C6-alkyl, m is 0, 1 or 2 and x is 0, 1 or 2.

[0070] 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 M and P are each independently selected from the group consisting of C(R 2 ) or N, U and W are each independently C or N, and X, Y, and Z are each independently C(R 3a ), N, N(R 3c), O, or S, where at least one of X, Y, and Z is N or N(R3 c ), and the bonds in the rings containing U, W, X, Y, and Z may be single or double bonds, valence permitting; 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 5 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 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 6 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 is selected from the group consisting of one or more R 6 and each R 2are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and R 3a 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 , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)OR D , or -S(O) x R D , or -C(O)R D and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, C1-C6 alkylene-cycloalkyl, heterocyclyl, C1-C6 alkylene-heterocyclyl, aryl, C1-C6 alkylene-aryl, heteroaryl, C1-C6 alkylene-heteroaryl, or -C(O)R D and each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 8 and each R 4 are independently hydrogen, C-C-alkyl, C-C-heteroalkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 11 and each R A are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and R B and R C each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl, -OR A , -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -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 7and 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 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 11 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0071] As generally described herein for formulas (I) and (II), A and B are each independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which may contain one or more R 1 is optionally replaced by

[0072] 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

[0073] 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

[0074] 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

[0075] 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.

[0076] 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 are R 1 is replaced by

[0077] 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 are R 1 is replaced by

[0078] 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 is optionally substituted with 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.

[0079] 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.

[0080] 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

[0081] In some embodiments, each of A and B is independently: [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.

[0082] In some embodiments, each of A and B is [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.

[0083] In some embodiments, one of A and B is independently: [ka] wherein each R 1 is as defined herein. In some embodiments, one of A and B is [ka] wherein each R 1aare independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and each alkyl, heteroalkyl, and haloalkyl is selected from one or more R 7 In some embodiments, one of A and B is independently [ka] where each R 1a are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and each alkyl, heteroalkyl, and haloalkyl is selected from one or more R 7 is optionally replaced by

[0084] In some embodiments, one of A and B is [ka] In some embodiments, one of A and B is independently selected from: [ka] In some embodiments, one of A and B is independently selected from: [ka] is.

[0085] In some embodiments, one of A and B is independently a monocyclic heterocyclyl or a bicyclic heterocyclyl, each of which is selected from the group consisting of one or more R 1 In some embodiments, one of A and B independently is optionally substituted with one or more R 1 In some embodiments, one of A and B independently is selected from the group consisting of one or more R1 In some embodiments, one of A and B is [ka] wherein R is independently selected from 1 is as defined herein. In some embodiments, one of A and B is [ka] wherein R is independently selected from 1 is as defined herein. In some embodiments, one of A and B is [ka] where R 1 is as defined herein. In some embodiments, A 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. In some embodiments, A is [ka] In some embodiments, A is selected from: [ka] In some embodiments, one of A and B is independently selected from: [ka] is.

[0086] As outlined herein, for formulas (I) and (II), L 1 and L 2 are each independently absent or C-C-alkylene, C-C-heteroalkylene, -O-, -C(O)-, -N(R 4 )-, -N(R 4 )C(O)- or -C(O)N(R 4 )-group, where each alkylene and heteroalkylene may be one or more R 5 is optionally replaced by

[0087] In some embodiments, L 1 is absent. In some embodiments, L 1 is C1-C6-alkylene (e.g., C1-alkylene, C2-alkylene, C3-alkylene, C4-alkylene, C5-alkylene, or C6-alkylene). 1 is an unsubstituted C1-C6 alkylene. In some embodiments, L 1 is a substituted C1-C6-alkylene, e.g., one or more R 5 In some embodiments, L is a C1-C6 alkylene substituted with 1 is one R 5 In some embodiments, L is a C1-alkylene substituted with 1 is —CH— (or methylene). In some embodiments, L 1 is —C(O)— (or carbonyl).

[0088] In some embodiments, L 1is absent, C1-C6-alkylene, C1-C6-heteroalkylene, -N(R 4 )C(O)-, or -C(O)N(R 4 )-, where each alkylene and heteroalkylene is selected from one or more R 5 is optionally replaced by

[0089] In some embodiments, L 1 is C1-C6 heteroalkylene (e.g., C1-heteroalkylene, C2-heteroalkylene, C3-heteroalkylene, C4-heteroalkylene, C5-heteroalkylene, or C6-heteroalkylene). 1 is unsubstituted C1-C6 heteroalkylene. In some embodiments, L 1 is a substituted heteroalkylene, e.g., one or more R 5 In some embodiments, the heteroalkylene includes one or more heteroatoms. In some embodiments, the heteroalkylene includes one or more of oxygen, sulfur, nitrogen, boron, silicon, or phosphorus. In some embodiments, L 1 is -N(R 4 )C(O)—. In some embodiments, L 1 is -C(O)N(R 4 In some embodiments, L 1 is -C(O)N(H)-.

[0090] In some embodiments, L 1 is oxygen. In some embodiments, L 1 is R 4 In some embodiments, L 1 is R 4 In some embodiments, L 1 is -N(R 4 )-, for example, -N(CH3)-. In some embodiments, L 1In some embodiments, L 1 is -O-.

[0091] In some embodiments, L 2 is absent, C1-C6-alkylene, C1-C6-heteroalkylene, -N(R 4 )C(O)-, or -C(O)N(R 4 )-, where each alkylene and heteroalkylene is selected from one or more R 5 In some embodiments, L 2 is unsubstituted C1-C6 heteroalkylene. In some embodiments, L 2 is a substituted heteroalkylene, e.g., one or more R 5 In some embodiments, the heteroalkylene includes one or more heteroatoms. In some embodiments, the heteroalkylene includes one or more of oxygen, sulfur, nitrogen, boron, silicon, or phosphorus. In some embodiments, L 2 is -N(R 4 )C(O)—. In some embodiments, L 2 is -C(O)N(R 4 In some embodiments, L 2 is -C(O)N(H)-.

[0092] In some embodiments, L 2 is R 4 In some embodiments, L 2 is R 4 In some embodiments, L 2 is -N(R 4 )-, for example, -N(CH3)-. In some embodiments, L 2 is -NH-.

[0093] As outlined herein, for formula (I), X, Y, and Z are each independently C(R3a ), C(R 3a )(R 3b ), N, or N(R 3c ), or O. In some embodiments, at least one of X, Y, and Z is N or N(R 3c In some embodiments, at least one of X, Y, and Z is O. In some embodiments, at least two of X, Y, and Z are N or N(R 3c In some embodiments, X is N. In some embodiments, X is N(R 3c In some embodiments, X is O. In some embodiments, X is C(R 3a ) (e.g., CH). In some embodiments, X is C(R 3a )(R 3b In some embodiments, Y is N. In some embodiments, Y is N(R 3c In some embodiments, Y is C(R 3a ) (e.g., CH). In some embodiments, Y is C(R 3a )C(R 3b ). In some embodiments, Z is N. In some embodiments, Z is N(R 3c In some embodiments, Z is C(R 3a ) (e.g., CH). In some embodiments, Z is C(R 3a )C(R 3b In some embodiments, two of X, Y, and Z are N and the other of X, Y, and Z is C(R 3a ) (e.g., CH). In some embodiments, one of X, Y, and Z is C(R 3a ) (e.g., CH), and the others of X, Y, and Z are each independently N. In some embodiments, X and Y are each independently N, and Z is C(R 3a ) (e.g., CH). In some embodiments, X is C(R3a ) (e.g., CH), and Y and Z are each independently N.

[0094] In some embodiments, X, Y, and Z are each independently N or C(R 3a ) where at least one of X, Y, and Z is N, and the bond in the ring containing X, Y, and Z can be a single or double bond, valence permitting.

[0095] In some embodiments, X is C(R 3a ) and Y is C(R 3a ) and Z is O. In some embodiments, X is C(R 3a ) and Y is C(R 3a ), Z is O, and y is 0. In some embodiments, X is C(R 3a ) and Y is C(R 3a ), Z is O, and the bond between X and Y is a double bond. In some embodiments, X is C(R 3a ) and Y is C(R 3a ), Z is O, and the bond between Y and Z is a single bond.

[0096] In some embodiments, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] is.

[0097] In some embodiments of Formulas (I) and (II), R 1 is hydrogen. In some embodiments, R 1 is C1-C6-alkyl. In some embodiments, R 1 is C-C-alkenyl. In some embodiments, R 1 is C2-C6-alkynyl. In some embodiments, R 1 is C1-C6-heteroalkyl. In some embodiments, R 1 is C-C-haloalkyl (e.g., —CF). In some embodiments, R 1 is C-alkyl (e.g., methyl). In some embodiments, R 1 is unsubstituted C-C-alkyl, unsubstituted C-C-alkenyl, unsubstituted C-C-alkynyl, unsubstituted C-C-heteroalkyl, or unsubstituted C-C-haloalkyl. 1 is one or more R 6 In some embodiments, R 1 is one or more R 6 In some embodiments, R 1 is one or more R 6 In some embodiments, R 1 is one or more R 6 In some embodiments, R is C-C-heteroalkyl substituted with 1 is one or more R 6In some embodiments, R 1 is methyl.

[0098] In some embodiments, R 1 is cycloalkyl (e.g., 3- to 7-membered cycloalkyl). In some embodiments, R 1 is heterocyclyl (e.g., 3- to 7-membered heterocyclyl). In some embodiments, R 1 is aryl. In some embodiments, R 1 is C1-C6 alkylene-aryl (e.g., benzyl). In some embodiments, R 1 is C1-C6 alkenylene-aryl. In some embodiments, R 1 is C1-C6 alkylene-heteroaryl. In some embodiments, R 1 is heteroaryl. In some embodiments, R 1 is an unsubstituted cycloalkyl, an unsubstituted heterocyclyl, an unsubstituted aryl, an unsubstituted C-C alkylene-aryl, an unsubstituted C-C alkenylene-aryl, an unsubstituted C-C alkylene-heteroaryl, or an unsubstituted heteroaryl. 1 is one or more R 6 In some embodiments, R 1 is one or more R 6 In some embodiments, R is a heterocyclyl substituted with 1 is one or more R 6 In some embodiments, R 1 is one or more R 6 In some embodiments, R 1 is one or more R 6 In some embodiments, R 1 is one or more R 6In some embodiments, R is a C1-C6 alkylene-heteroaryl substituted with 1 is one or more R 6 and heteroaryl substituted with

[0099] In some embodiments, R 1 -OR A In some embodiments, R 1 is -NR B R C (e.g., NH or NMe). In some embodiments, R 1 is -NR B C(O)R D In some embodiments, R 1 is -C(O)NR B R C In some embodiments, R 1 is -C(O)R D In some embodiments, R 1 is -C(O)OR D In some embodiments, R 1 -SR E In some embodiments, R 1 is -S(O) x R D In some embodiments, R 1 is halo, e.g., fluoro, chloro, bromo, or iodo. In some embodiments, R 1 is cyano. In some embodiments, R 1 is nitro (—NO). In some embodiments, R 1 is oxo.

[0100] In some embodiments, two R 1 The groups, together with the atom to which they are attached, form a 3- to 7-membered cycloalkyl. In some embodiments, two R 1 The groups, together with the atoms to which they are attached, form a 3- to 7-membered heterocyclyl.1 The groups, together with the atoms to which they are attached, form a 5- or 6-membered aryl. In some embodiments, two R 1 The groups, together with the atoms to which they are attached, form a 5- or 6-membered heteroaryl. A cycloalkyl, heterocyclyl, aryl, or heteroaryl can be joined by one or more R 6 may be substituted with

[0101] In some embodiments of Formulas (I) and (II), R 2 is hydrogen. In some embodiments, R 2 is halo (e.g., fluoro, chloro, bromo, or iodo). In some embodiments, R 2 is cyano. In some embodiments, R 2 is C1-C6-alkyl. In some embodiments, R 2 is C-C-alkenyl. In some embodiments, R 2 is C2-C6-alkynyl. In some embodiments, R 2 -OR A (e.g., —OH).

[0102] In some embodiments, R 3a , R 3b , or both are independently hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D In some embodiments, R 3a and R 3b are each independently hydrogen or C-C-alkyl. 3a is hydrogen. In some embodiments, R 3b is hydrogen. In some embodiments, R 3ais C1-C6-alkyl (e.g., methyl). In some embodiments, R 3b is C1-C6-alkyl (e.g., methyl). In some embodiments, R 3a is halo (e.g., fluoro, chloro, bromo, or iodo). In some embodiments, R 3b is halo (e.g., fluoro, chloro, bromo, or iodo). In some embodiments, R 3a is cyano. In some embodiments, R 3b is cyano. In some embodiments, R 3a -OR A (e.g., —OH). In some embodiments, R 3b -OR A (e.g., —OH). In some embodiments, R 3a is -NR B R C In some embodiments, R 3b is -NR B R C In some embodiments, R 3a is -C(O)R D In some embodiments, R 3b is -C(O)R D In some embodiments, R 3a is -C(O)OR D In some embodiments, R 3b is -C(O)OR D In some embodiments, R 3a and R 3b taken together with the carbon atom to which they are attached form an oxo group.

[0103] In some embodiments, R 3c is hydrogen. In some embodiments, R 3c is C1-C6-alkyl. In some embodiments, R 3c is methyl. In some embodiments, R 3cis not hydrogen. 3c is not methyl. In some embodiments, R 3c is C1-C6 alkyl. In some embodiments, R 3c is one or more R 8 C1-C6 substituted with

[0104] In some embodiments, R 4 is hydrogen. In some embodiments, R 4 is C1-C6 alkyl. In some embodiments, R 4 is C1-C6 haloalkyl (e.g., -CF3 or -CHF2). In some embodiments, R 4 is methyl.

[0105] In some embodiments, R 5 is hydrogen. In some embodiments, R 5 is C1-C6-alkyl. In some embodiments, R 5 is C1-C6-heteroalkyl. In some embodiments, R 5 is C-C-haloalkyl. In some embodiments, R 5 is cycloalkyl. In some embodiments, R 5 is halo (e.g., fluoro, chloro, bromo, or iodo). In some embodiments, R 5 is cyano. In some embodiments, R 5 is oxo. In some embodiments, R 5 -OR A In some embodiments, R 5 is -NR B R C In some embodiments, R 5 is -C(O)R D or -C(O)OR D is.

[0106] In some embodiments, R 6 is C1-C6-alkyl. In some embodiments, R 6 is C-C-alkenyl. In some embodiments, R 6 is C2-C6-alkynyl. In some embodiments, R 6 is C1-C6-heteroalkyl. In some embodiments, R 6 is C-C-haloalkyl. In some embodiments, R 6 is unsubstituted C-C-alkyl, unsubstituted C-C-alkenyl, unsubstituted C-C-alkynyl, unsubstituted C-C-haloalkyl, or unsubstituted C-C-heteroalkyl. 6 is one or more R 11 In some embodiments, R 6 is one or more R 11 In some embodiments, R 6 is one or more R 11 In some embodiments, R 6 is one or more R 11 In some embodiments, R 6 is one or more R 11 is a C1-C6-heteroalkyl substituted with

[0107] In some embodiments, R 6 is cycloalkyl. In some embodiments, R 6 is heterocyclyl. In some embodiments, R 6 is aryl. In some embodiments, R 6 is heteroaryl. In some embodiments, R 6 is an unsubstituted cycloalkyl, an unsubstituted heterocyclyl, an unsubstituted aryl, or an unsubstituted heteroaryl. In some embodiments, R 6is one or more R 11 In some embodiments, R 6 is one or more R 11 In some embodiments, R is a heterocyclyl substituted with 6 is one or more R 11 In some embodiments, R 6 is one or more R 11 and heteroaryl substituted with

[0108] In some embodiments, R 6 is halo (e.g., fluoro, chloro, bromo, or iodo). In some embodiments, R 6 is cyano. In some embodiments, R 6 is oxo. In some embodiments, R 6 -OR A In some embodiments, R 6 is -NR B R C In some embodiments, R 6 is -NR B C(O)R D In some embodiments, R 6 is —NO. In some embodiments, R 6 is -C(O)NR B R C In some embodiments, R 6 is -C(O)R D In some embodiments, R 6 is -C(O)OR D In some embodiments, R 6 -SR E In some embodiments, R 6 is -S(O) x R D is.

[0109] In some embodiments, R 7is C1-C6-alkyl. In some embodiments, R 7 is halo (e.g., fluoro, chloro, bromo, or iodo). In some embodiments, R 7 is cyano. In some embodiments, R 7 is oxo. In some embodiments, R 7 -OR A1 (e.g., —OH).

[0110] In some embodiments, R 11 is C1-C6-alkyl. In some embodiments, R 11 is C1-C6-heteroalkyl. In some embodiments, R 11 is C-C-haloalkyl (e.g., —CF). In some embodiments, R 11 is cycloalkyl. In some embodiments, R 11 is heterocyclyl. In some embodiments, R 11 is aryl. In some embodiments, R 11 is heteroaryl. In some embodiments, R 11 is halo. In some embodiments, R 11 is cyano. In some embodiments, R 11 is oxo. In some embodiments, R 11 -OR A is.

[0111] In some embodiments of Formulas (I) and (II), R A is hydrogen. In some embodiments, R A is C1-C6-alkyl (e.g., methyl). In some embodiments, R A is C1-C6 haloalkyl. In some embodiments, R A is aryl. In some embodiments, R A is heteroaryl. In some embodiments, RA is C1-C6 alkylene-aryl (e.g., benzyl). In some embodiments, R A is C1-C6 alkylene-heteroaryl. In some embodiments, R A is C(O)R D In some embodiments, R A is -S(O) x R D is.

[0112] In some embodiments, R B , R C , or both, independently, hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, cycloalkyl, heterocyclyl, or -OR A In some embodiments, R B and R C Each of R is independently hydrogen. B and R C Each of is independently C1-C6 alkyl. In some embodiments, R B and R C is hydrogen and R B and R C and the other is C1-C6 alkyl. In some embodiments, R B and R C together with the atoms to which they are attached form one or more R 7 forms a 3- to 7-membered heterocyclyl ring optionally substituted with

[0113] In some embodiments, R D , R E , or both 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 (e.g., benzyl), or C-C alkylene-heteroaryl. D and RE Each of R is independently hydrogen. D and R E Each of is independently C1-C6 alkyl. In some embodiments, R D is hydrogen. In some embodiments, R E is hydrogen. In some embodiments, R D is C1-C6 alkyl (e.g., methyl). In some embodiments, R E is C1-C6 alkyl (e.g., methyl). In some embodiments, R D is C1-C6 heteroalkyl. In some embodiments, R E is C1-C6 heteroalkyl. In some embodiments, R D is C1-C6 haloalkyl. In some embodiments, R E is C1-C6 haloalkyl. In some embodiments, R D is cycloalkyl. In some embodiments, R E is cycloalkyl. In some embodiments, R D is heterocyclyl. In some embodiments, R E is heterocyclyl. In some embodiments, R D is aryl. In some embodiments, R E is aryl. In some embodiments, R D is heteroaryl. In some embodiments, R E is heteroaryl. In some embodiments, R D is C1-C6 alkylene-aryl (e.g., benzyl). In some embodiments, R E is C1-C6 alkylene-aryl (e.g., benzyl). In some embodiments, R D is C1-C6 alkylene-heteroaryl. In some embodiments, R E is a C1-C6 alkylene-heteroaryl.

[0114] In some embodiments, R A1 is hydrogen. In some embodiments, R A1 is C1-C6-alkyl (e.g. methyl).

[0115] In some embodiments, m is 0, 1, or 2. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, x is 0, 1, or 2. In some embodiments, x is 0. In some embodiments, x is 1. In some embodiments, x is 2. In some embodiments, y is 0 or 1. In some embodiments, y is 0.

[0116] In some embodiments, the compound of Formula (I) is a compound of 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 X, Y, and Z are each independently C(R 3a ), C(R 3a )(R 3b ), N, N(R 3c ), or O, where at least one of X, Y, and Z is N, N(R 3c ), or O, and the bonds in the ring containing X, Y, and Z may be single or double bonds, valence permitting; L 1 is absent, C1-C6-alkylene, C1-C6-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 5 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 , -SR E , 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 6 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 is selected from the group consisting of one or more R 6 and each R 2 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and R 3a and R 3b are each independently hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D, or -C(O)OR D or R 3a and R 3b together with the carbon atom to which they are attached form an oxo group, and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, C1-C6 alkylene-cycloalkyl, heterocyclyl, C1-C6 alkylene-heterocyclyl, aryl, C1-C6 alkylene-aryl, heteroaryl, C1-C6 alkylene-heteroaryl, or -C(O)R D and each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 8 and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , 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 11 and each R 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 8 is C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , or -S(O) x R D and each R 11 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 R B and R C each independently represents hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, or -OR A or R B and R C together with the atoms to which they are attached form one or more R 7 and each RD and R E 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 A1 is hydrogen or C1-C6-alkyl, m is 0, 1 or 2 and x is 0, 1 or 2.

[0117] In some embodiments, the compound of Formula (I) is a compound of 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 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 5 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)NRB R C , -C(O)R D , -C(O)OR D , -SR E , 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 6 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 is selected from the group consisting of one or more R 6 and each R 2 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, C1-C6 alkylene-cycloalkyl, heterocyclyl, C1-C6 alkylene-heterocyclyl, aryl, C1-C6 alkylene-aryl, heteroaryl, C1-C6 alkylene-heteroaryl, or -C(O)R D and each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 8 and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , 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 11 and each R 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 8 is C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , or -S(O) x R D and each R 11 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -ORA 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 R B and R C each independently represents hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, or -OR A or R B and R C together with the atoms to which they are attached form one or more R 7 and each R D and R E 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 A1 is hydrogen or C1-C6-alkyl, m is 0, 1 or 2 and x is 0, 1 or 2.

[0118] In some embodiments, the compound of Formula (I) is a compound of 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 each R 1are 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 , -SR E , 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 6 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 is selected from the group consisting of one or more R 6 and each R 2 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, C1-C6 alkylene-cycloalkyl, heterocyclyl, C1-C6 alkylene-heterocyclyl, aryl, C1-C6 alkylene-aryl, heteroaryl, C1-C6 alkylene-heteroaryl, or -C(O)R Dand each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 8 and each R 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , 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 11 and each R 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 8 is C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , or -S(O) x R D and each R 11are 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 R B and R C each independently represents hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, or -OR A or R B and R C together with the atoms to which they are attached form one or more R 7 and each R D and R E 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 A1 is hydrogen or C1-C6-alkyl, m is 0, 1 or 2 and x is 0, 1 or 2.

[0119] In some embodiments, the compound of Formula (I) is a compound of Formula (Id): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, and B is cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 and each R 1are 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 , -SR E , 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 6 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 is selected from the group consisting of one or more R 6 and each R 2 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, C1-C6 alkylene-cycloalkyl, heterocyclyl, C1-C6 alkylene-heterocyclyl, aryl, C1-C6 alkylene-aryl, heteroaryl, C1-C6 alkylene-heteroaryl, or -C(O)R Dand each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 8 and each R 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , 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 11 and each R 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 8 is C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , or -S(O) x R D and each R 11are 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 R B and R C each independently represents hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, or -OR A or R B and R C together with the atoms to which they are attached form one or more R 7 and each R D and R E 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 A1 is hydrogen or C1-C6-alkyl, m is 0, 1 or 2 and x is 0, 1 or 2.

[0120] In some embodiments, the compound of Formula (I) is a compound of Formula (Ie): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, and A is cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 and each R 1are 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 , -SR E , 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 6 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 is selected from the group consisting of one or more R 6 and each R 2 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, C1-C6 alkylene-cycloalkyl, heterocyclyl, C1-C6 alkylene-heterocyclyl, aryl, C1-C6 alkylene-aryl, heteroaryl, C1-C6 alkylene-heteroaryl, or -C(O)R Dand each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 8 and each R 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , 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 11 and each R 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 8 is C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , or -S(O) x R D and each R 11are 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 R B and R C each independently represents hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, or -OR A or R B and R C together with the atoms to which they are attached form one or more R 7 and each R D and R E 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 A1 is hydrogen or C1-C6-alkyl, m is 0, 1 or 2, p is 0, 1, 2 or 3 and x is 0, 1 or 2.

[0121] In some embodiments, the compound of formula (I) is a compound of formula (If): [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 1and optionally replaced by L 2 is absent, C1-C6-alkylene, C1-C6-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 5 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 , -SR E , 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 6 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 is selected from the group consisting of one or more R 6 and each R 2 are independently hydrogen, C-C-alkyl, C-C-alkenyl, C-C-alkynyl, C-C-heteroalkyl, C-C-haloalkyl, halo, cyano, -N(R B )(R C ), or -ORA and R 3a is hydrogen, C1-C6-alkyl, 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 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, C1-C6 alkylene-cycloalkyl, heterocyclyl, C1-C6 alkylene-heterocyclyl, aryl, C1-C6 alkylene-aryl, heteroaryl, C1-C6 alkylene-heteroaryl, or -C(O)R D and each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 8 and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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)ORD , -SR E , 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 11 and each R 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 8 are independently C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , or -S(O) x R D and each R 11 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 R B and R C each independently represents hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, or -OR A or R B and R Ctogether with the atoms to which they are attached form one or more R 7 and each R D and R E 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 A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0122] In some embodiments, R 2 is halo. In some embodiments, R 2 is fluoro. In some embodiments, R 2 -OR A In some embodiments, R 2 is -N(R B )(R C )

[0123] In some embodiments, the compound of Formula (I) is a compound of Formula (Ig): [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 2 is absent, C1-C6-alkylene, C1-C6-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 5 and each R 1are 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 , -SR E , 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 6 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 is selected from the group consisting of one or more R 6 and each R 2 are independently hydrogen, C-C-alkyl, C-C-alkenyl, C-C-alkynyl, C-C-heteroalkyl, C-C-haloalkyl, halo, cyano, -N(R B )(R C ), or -OR A and R 3a is hydrogen, C1-C6-alkyl, 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 3cis hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, C1-C6 alkylene-cycloalkyl, heterocyclyl, C1-C6 alkylene-heterocyclyl, aryl, C1-C6 alkylene-aryl, heteroaryl, C1-C6 alkylene-heteroaryl, or -C(O)R D and each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 8 and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , 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 11 and each R 7is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 8 are independently C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , or -S(O) x R D and each R 11 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 R B and R C each independently represents hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, or -OR A or R B and R C together with the atoms to which they are attached form one or more R 7 and each R D and R Eare 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 A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0124] In some embodiments, the compound of Formula (I) is a compound of Formula (Ih): [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 2 is absent, C1-C6-alkylene, C1-C6-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 5 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 , -SRE , 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 6 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 is selected from the group consisting of one or more R 6 and each R 2 are independently hydrogen, C-C-alkyl, C-C-alkenyl, C-C-alkynyl, C-C-heteroalkyl, C-C-haloalkyl, halo, cyano, -N(R B )(R C ), or -OR A and R 3a is hydrogen, C1-C6-alkyl, 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 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, C1-C6 alkylene-cycloalkyl, heterocyclyl, C1-C6 alkylene-heterocyclyl, aryl, C1-C6 alkylene-aryl, heteroaryl, C1-C6 alkylene-heteroaryl, or -C(O)R D and each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 8 and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R5 are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , 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 11 and each R 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 8 are independently C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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 , -SR E , or -S(O) x RD and each R 11 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 R B and R C each independently represents hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, or -OR A or R B and R C together with the atoms to which they are attached form one or more R 7 and each R D and R E 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 A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0125] In some embodiments of any one of Formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), and (Ig), R 3c is not hydrogen or methyl. 3c is not hydrogen. 3c is not methyl. In some embodiments, R 3cis not ethyl. In some embodiments, the compound of Formula (I) is not compound 143, 207, 208, 209, 210, 211, 212, 228, 229, 230, 231, 234, 235, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 249, 250, 251, 252, 253, 258, 259, 260, 269, 270, 272, 273, 274, 275, 277, 278, 279, 280, 281, 284, 285, 286, or 287. In some embodiments, the compound of Formula (I) is not compound 284.

[0126] 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 1-69

Table 1-90

Table 1-97

Table 1-100

Table 1-110

[0127] In some embodiments, the compound of Formula (I) is selected from compounds 288-363. In some embodiments, the compound of Formula (I) is selected from compounds 118, 119, 140, 141, 142, 143, 145, 146, 147, 148, 149, 150, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 217, 218, 219, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 2 4, 235, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 249, 250, 251, 252, 253, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, or 287. In some embodiments, the compound of Formula (I) is selected from 141, 143, 190, 198, 202, 207, 208, 209, 210, 228, 229, 234, 237, 239, 240, 242, 243, 246, 250, 251, 252, 255, 258, 260, 266, 269, 272, 275, 277, 278, 279, 284, 285, 288, 293, 293, 294, 296, 298, 301, 302, 306, 310, 312, 314, 315, 350, and 351.

[0128] In some embodiments, the compound of Formula (I) is a) Compound 288, b) Compound 289, c) Compound 290, d) Compound 291, e) Compound 292, f) Compound 293, g) Compound 294, h) Compound 295, i) Compound 296, j) Compound 297, k) Compound 298, l) Compound 299, m) Compound 300, n) Compound 301, o) Compound 302, p) Compound 303, q) Compound 304, r) Compound 305, s) Compound 306, t) Compound 307, Compound 307, u) Compound 308, v) Compound 309, w) Compound 310, x) Compound 311, y) Compound 312, z) Compound 313, aa) Compound 314, bb) Compound 315, cc) Compound 316, dd) Compound 317 , ee) compound 318, ff) compound 319, gg) compound 320, hh) compound 321, ii) compound 322, jj) compound 323, kk) compound 324, ll) compound 325, mm) compound 326, nn) ​​compound 327 , oo) compound 328, pp) compound 329, qq) compound 330, compound rr) compound 331, ss) compound 332, tt) compound 333, uu) compound 334, vv) compound 335, ww) compound 336, xx) compound Compound 337, yy) Compound 338, zz) Compound 339, aaa) Compound 340, bbb) Compound 341, ccc) Compound 342, ddd) Compound 343, eee) Compound 344, fff) Compound 345, ggg) Compound 346, hhh) Compound 347, iii) Compound 348, jjj) Compound 349, kkk) Compound 350, lll) Compound 351, mmm) Compound 352, nnn) Compound 353, ooo) Compound 354, ppp) Compound 355, qqq) Compound 356, rrr) Compound 357, sss) Compound 358, ttt) Compound 359, uuu) Compound 360, vvv) Compound 361, www) Compound 362, or xxx) Compound 363.

[0129] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., imidazo[1,2-b]pyridazinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and Compound (Ii) is Compound 118, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0130] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., imidazo[1,2-b]pyridazinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X and Y are each independently C(R 3a ) (e.g., CH), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is Compound 119, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0131] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., imidazo[1,2-b]pyridazinyl), and L 1 is absent or -N(R 4 )- and L 2 is absent or -C(O)N(R 4 )—(e.g., —C(O)N(H)—). In some embodiments, for Formula (I), the compound is selected from compounds 118, 141, 228, 229, 242, 243, 269, and 277.

[0132] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), where X is N and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ie), (If), and (Ii) is Compound 140, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0133] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), where X is O and Y is C(R 3a ) (e.g., C(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ie), (If), and (Ii) is Compound 141, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0134] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is Compound 142, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0135] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 143, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0136] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is Compound 145, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0137] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is N(R 3c ) (e.g., NH), and Y is C(R 3a ) (e.g., C(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ie), (If), and (Ii) is Compound 146, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0138] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is N(R 3c ) (e.g., NH), Y is N, Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ie), (If), and (Ii) is Compound 147, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0139] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is Compound 148, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0140] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., CH), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is Compound 149, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0141] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), where X is N and Y is C(R 3a ) (e.g., CH), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ie), (If), and (Ii) is Compound 150, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0142] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), where X is O and Y is C(R 3a ) (e.g., C(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ie), (If), and (Ii) is compound 187, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0143] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a )(R 3b ) (e.g., CH2), and Y is C(R 3a )(R 3b ) (e.g., CH), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ie), (If), and (Ii) is compound 188, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0144] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 1-methylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 189, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0145] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2-methylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is Compound 190, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0146] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 1,2-dimethylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is Compound 191, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0147] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2-ethylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is Compound 192, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0148] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2,2-dimethylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 193, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0149] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., 4,7-diazaspiro[2.5]octanyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 194, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0150] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is Compound 195, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0151] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 4-(N-ethyl)aminopiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is Compound 196, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0152] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 4-(N-tert-butyl)aminopiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 197, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0153] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 4-(N,N-dimethyl)aminopiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is Compound 198, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0154] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., octahydropyrrolo[1,2-a]pyrazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is Compound 199, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0155] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 1-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 1 is -N(R 4 )-(e.g., -N(CH3)-), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I) and (Ia) is compound 200, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0156] In some embodiments, for Formula (I), A is a bicyclic 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 is -N(R 4 )-(e.g., -N(CH3)-), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I) and (Ia) is compound 201, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0157] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 3-(N,N-dimethyl)aminopyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 202, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0158] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 3-(N-tert-butyl)aminopyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 203, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0159] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 1,3′-bipyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 204, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0160] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., 2,6-diazaspiro[3.3]heptanyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 205, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0161] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., 2-methyl-2,6-diazaspiro[3.3]heptanyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 206, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0162] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 1-methylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4)—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 207, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0163] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 208, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0164] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 1-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 209, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0165] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 1-ethylpiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 210, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0166] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2,6-dimethylpiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 211, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0167] 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 212, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0168] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 4-fluoro-2-methyl-2H-indazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 217, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0169] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 4-fluoro-2-methylbenzo[d]oxazolyl), and L 2 is -C(O)N(R4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 218, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0170] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 4-fluoro-2-methylbenzo[d]thiazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 219, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0171] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2-methylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 228, 352, 353, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0172] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 1,2-dimethylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 229, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0173] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 230, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0174] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 4-fluoro-2-methyl-2H-indazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 231, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0175] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 4-fluoro-2-methylbenzo[d]oxazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 234, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0176] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 4-fluoro-2-methylbenzo[d]thiazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 235, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0177] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 237, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0178] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 238, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0179] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2-ethylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 239, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0180] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2,2-dimethylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 240, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0181] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., 4,7-diazaspiro[2.5]octanyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 241, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0182] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., 2,6-diazaspiro[3.3]heptanyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 242, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0183] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., 2-methyl-2,6-diazaspiro[3.3]heptanyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 243, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0184] 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 is -N(R 4 )-(e.g., -N(CH3)-), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 244, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0185] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 1 is -N(R 4 )-(e.g., -N(CH3)-), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 245, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0186] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2-methylimidazo[1,2-a]pyrazinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 246, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0187] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 4,6-dimethylpyrazolo[1,5-a]pyrazinyl), and L 2 is -C(O)N(R4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 247, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0188] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 3-(N-tert-butyl)-aminopyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) 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 heterocyclyl (e.g., octahydropyrrolo[1,2-a]pyrazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 250, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0190] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 4-(N,N-dimethyl)aminopiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 251, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0191] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 4-(N-ethyl)aminopiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 252, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0192] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 6,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) 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 heterocyclyl (e.g., (1R,5S)-3,8-diazabicyclo[3.2.1]octanyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 255, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0194] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 1-methylpiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 256, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0195] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 1-ethylpiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 257, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0196] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 3-(N,N-methyl)aminopyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 258, 350, 351, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0197] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 4-(N-tert-butyl)aminopiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 259, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0198] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., (1R,5S)-3,8-diazabicyclo[3.2.1]octanyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 260, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0199] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 261, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0200] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 262, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0201] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2-methylimidazo[1,2-a]pyrazinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 263, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0202] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 6,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (Ig), and (Ih) is compound 264, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0203] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 4,6-dimethylpyrazolo[1,5-a]pyrazinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (Ig), and (Ih) is compound 265, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0204] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 266, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0205] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 8-methyl-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 267, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0206] In some embodiments, for Formula (I), A is monocyclic heterocyclyl (e.g., piperazinyl), B is monocyclic heteroaryl (e.g., pyrazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), and (Ih) is compound 268, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0207] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 269, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0208] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., piperazinyl), B is a monocyclic heteroaryl (e.g., pyrazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), and (Ie) is compound 270, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0209] 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), (Ie), (If), (Ih), and (Ii) is compound 271, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0210] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 1,3′-bipyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 272, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0211] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 6,8-dimethylimidazo[1,2-a]pyrazinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 273, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0212] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4)—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 274, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0213] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 275, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0214] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2-methylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 277, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0215] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 3-(N,N-dimethyl)aminopyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 278, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0216] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., (1R,5S)-3,8-diazabicyclo[3.2.1]octanyl), B is a bicyclic heteroaryl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 279, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0217] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), and (Ie) is compound 280, 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]pyridazinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), and (Ie) is compound 281, 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]pyridazinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), and (Ie) 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., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), B is a monocyclic heterocyclyl (e.g., piperidinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is C(R 3a ) (e.g., C(CH3)), Z is O, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Ic), and (Ie) is compound 283, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0221] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CHCH)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 284, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0222] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperidinyl), B is a bicyclic heteroaryl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 285, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0223] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NH), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 286, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0224] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 1-methylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NH), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 287, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0225] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CHCH)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 288, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0226] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., (1R,5S)-3,8-diazabicyclo[3.2.1]octanyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CHCH)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 289, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0227] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH(CH3)2)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 290, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0228] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CHCHOH)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 291, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0229] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH2CHOCH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 292, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0230] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-a]pyrazinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 293, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0231] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ), where R 3c is C1-C6-cycloalkyl (e.g., cyclopropyl), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 294, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0232] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ), where R 3c is heterocyclyl (e.g., oxetane), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 295, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0233] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 3-(N-cyclopropyl)aminopyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 296, 371, 372, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0234] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., C(CH3)), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 297, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0235] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 3-(N-methyl)aminopyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 298, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0236] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., 1,6-diazaspiro[3.4]octanyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 299, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0237] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, and R 2is C1-C6 alkyl (e.g., CH3), y is 0, and m is 1. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 300, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0238] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., 1,7-diazaspiro[3.5]nonanyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 301, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0239] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CH2CH2CH2OCH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 302, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0240] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, and R 2 is halo (e.g., F), y is 0, and m is 1. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 303, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0241] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) and R 3cis tetrahydro-2H-pyranyl, Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 304, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0242] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NCH2CH2F), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 305, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0243] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., NCH2CH2OCH3), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 306, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0244] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 4-(N-ethyl)aminopiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NCH2CH2OCH3), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 307, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0245] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) and R 3c is R 8 C1-C6 alkyl substituted with R 8is heterocyclyl (e.g., oxetanyl), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 308, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0246] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NCH2C(O)N(CH3)2), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 309, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0247] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 3-(N-ethyl)aminopyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., NCH2CH2OCH3), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 310, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0248] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, and R 2 -OR A (e.g., OCH3), y is 0, and m is 1. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 311, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0249] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., NCH2CH2CH2CH3), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 312, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0250] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) and R 3c is R 8 C1-C6-alkyl substituted with R 8 is heteroaryl (e.g., pyridyl), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 313, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0251] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 8-cyano-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 314, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0252] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-6-methoxy-2-methyl-2H-indazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 315, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0253] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CHCF)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 316, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0254] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) and R 3c is R 8 C1-C6 alkyl substituted with R 8 is heterocyclyl (e.g., oxiranyl), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 317, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0255] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) and R 3c is R 8 C1-C6 alkyl substituted with R 8 is heteroaryl (e.g., pyrimidyl), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 318, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0256] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 319, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0257] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 320, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0258] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 1,2,4-trimethyl-1H-benzo[d]imidazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 321, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0259] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 322, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0260] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 8-methoxy-2-methylimidazo[1,2-a]pyrazinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 323, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0261] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 324, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0262] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 6-hydroxy-2,7-dimethyl-2H-indazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 325, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0263] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 326, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0264] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 3-methaneaminopyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 327, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0265] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 4-(N-acyl)aminopiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4)—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 328, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0266] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CHCH(OH)CH(OH))), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 329, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0267] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 3-(N,N-diethyl)aminopyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CH2CHOCH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 330, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0268] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CHCOOH)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 331, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0269] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 4-fluoro-1,2-dimethyl-1H-benzo[d]imidazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 332, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0270] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 333, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0271] 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 334, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0272] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 4-methaneaminopiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 335, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0273] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 4-methyl-4 aminopiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 336, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0274] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CHCHCl)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 337, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0275] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) and R 3c is R 8 C1-C6 alkyl substituted with R 8 is heterocyclyl (e.g., oxetanyl), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 338, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0276] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CHC(O)CH)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 339, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0277] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) and R 3c is R 8 C1-C6 alkyl substituted with R 8 is heteroaryl (e.g., 1H-indazolyl), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 340, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0278] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) and R 3c is R 8 C1-C6 alkyl substituted with R 8is heteroaryl (e.g., pyrazolyl), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 341, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0279] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 2-methylimidazo[1,2-a]pyrazine-8(7H)-I), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 342, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0280] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-7-methoxy-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 343, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0281] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 6-methoxy-2,7-dimethyl-2H-indazolyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 344, 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., 4-(N-cyclopropyl)aminopiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 345, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0283] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 4-fluoro-3-(N-methylamino)pyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 346, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0284] In some embodiments, for Formula (I), A is —N(R B )(R C ) (e.g., —NH(CH2-py)), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L is a monocyclic heterocyclyl (e.g., piperidinyl) substituted with 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 347, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0285] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., 2,7-diazaspiro[3.5]nonanyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 348, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0286] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., 1,8-diazaspiro[4.5]decanyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH3)), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 349, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0287] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CHC(CH(OH))), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 354, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0288] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) and R 3c is R 8 cycloalkyl (e.g., cyclobutyl) substituted with R 8 is OR A (e.g., OH), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 355, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0289] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c );R 3cis heterocyclyl (e.g., tetrahydrofuranyl), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 356, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0290] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NCHCH(OH)CH), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 357, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0291] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) and R 3c is R 8 C1-C6 alkyl substituted with one R 8 is cycloalkyl (e.g., cyclobutyl), and one R 8 -OR A(e.g., —OH), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 358, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0292] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl), B is a bicyclic heteroaryl (e.g., 8-hydroxy-2-methylimidazo[1,2-a]pyrazinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NCH3), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 359, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0293] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NCH3), Z is N, and R 2 is OR A(e.g., OH), y is 0, and m is 1. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 360, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0294] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NCH3), Z is N, and R 2 is halo (e.g., F), y is 0, and m is 1. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 361, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0295] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NCH3), Z is N, and R 2 is -N(R B )(R C) (e.g., —NH(CH3)), y is 0, and m is 1. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 362, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0296] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) and R 3c is C1-C6 alkyl (e.g., vinyl), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 363, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0297] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CHCFCH), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 364, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0298] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) and R 3c is R 8 cycloalkyl (e.g., cyclobutyl) substituted with R 8 is heterocyclyl (e.g., oxetanyl), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 365, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0299] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) and R 3c is R 8 C1-C6 alkyl substituted with R 8is heteroaryl (e.g., oxazolyl), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 366, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0300] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CHCH(CH)OCH), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 367, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0301] In some embodiments, for Formula (I), 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 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) and R 3c is R 8 C1-C6 alkyl substituted with R 8is heteroaryl substituted with C-C alkyl (e.g., 1H-1,2,3-triazolyl), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 368, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0302] In some embodiments, for Formula (I), A is —NR B R C (e.g., —NHCHCHOH), B is a monocyclic heterocyclyl (e.g., piperidinyl) substituted with 8-fluoro-2-methylimidazo[1,2-a]pyridinyl, and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 369, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0303] In some embodiments, for Formula (I), A is —NR B R C (e.g., —NH) and haloalkyl (e.g., —CF), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., N(CH), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 370, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0304] In some embodiments, for Formula (I), A is —NR B R C (e.g., —NHC(CHCH)CHF), B is a monocyclic heterocyclyl (e.g., pyrrolidinyl) substituted with (e.g., —NHC(CHCH)CHF), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., N(CH), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 373, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0305] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 3-(N-methyl)aminopyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., NCH2CH3), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 374, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0306] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 3-(N,N-dimethyl)aminopyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NCH2CH3), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 375, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0307] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 4-(N-cyclopropyl)aminopiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c) (e.g., NCH2CH3), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 376, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0308] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 2,6-dimethylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NCH2CH3), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 377, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0309] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 1-methylpiperazinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NCH2CH3), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 378, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0310] In some embodiments, for Formula (I), A is a bicyclic heterocyclyl (e.g., 4,7-diazaspiro[2.5]octanyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NCH2CH3), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 379, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0311] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 4-(N-ethyl)aminopiperidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L 2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NCH2CH3), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 378, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0312] In some embodiments, for Formula (I), A is a monocyclic heterocyclyl (e.g., 3-aminopyrrolidinyl), B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl), and L2 is -C(O)N(R 4 )—(e.g., —C(O)N(H)—), and X is C(R 3a ) (e.g., CH), and Y is N(R 3c ) (e.g., NCH3), Z is N, y is 0, and m is 0. In some embodiments, the compound of Formula (I), (Ia), (Ib), (Id), (Ie), (If), (Ii), and (Ij) is compound 381, 382, ​​or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0313] The present disclosure further features a compound of formula (II). 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 M and P are each independently selected from the group consisting of C(R 2 ) or N, U and W are each independently C or N, and X, Y, and Z are each independently C(R 3a ), N, N(R 3c ) or S, where at least one of X, Y, and Z is N or N(R 3c ), and the bonds in the rings containing U, W, X, Y, and Z may be single or double bonds, valence permitting; 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 5and 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 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 6 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 is selected from the group consisting of one or more R 6 and each R 2 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and R 3a 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 , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)ORD , or -S(O) x R D , or -C(O)R D and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -S(O) x R D , or -C(O)R D and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 11 and each R Aare independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and R B and R C each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl, -OR A , -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -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 7 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 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 11 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0314] In some embodiments of Formula (II), [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] In some embodiments, [ka] teeth, [ka] is.

[0315] 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 may contain one or more R 1 M and P are each independently selected from the group consisting of C(R 2 ) or N, and X, Y, and Z are each independently C(R 3a ), N, N(R 3c ) or S, where at least one of X, Y, and Z is N or N(R 3c ), the bonds in the ring containing X, Y, and Z may be single or double bonds, valence permitting; L 1 and L 2 each independently represents absence, C-C-alkylene, C-C-heteroalkylene, —O—, —C(O)—, —N(R 4 )-, -N(R4 )C(O)-, or -C(O)N(R 4 )-, where each alkylene and heteroalkylene is selected from one or more R 5 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 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 6 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 is selected from the group consisting of one or more R 6 and each R 2 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and R 3a 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, -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)OR D , or -S(O) x R D , or -C(O)R D and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -S(O) x R D , or -C(O)R D and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 11and each R A are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and R B and R C each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl, -OR A , -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -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 7 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 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 11 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0316] 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 and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which may contain one or more R 1 M and P are each independently selected from the group consisting of C(R 2 ) or N, and X, Y, and Z are each independently C(R 3a ), N, N(R 3c ) or S, where at least one of X, Y, and Z is N or N(R 3c ), the bonds in the ring containing X, Y, and Z may be single or double bonds, 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 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 6 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 is selected from the group consisting of one or more R 6 and each R 2 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and R 3a 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 , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)OR D , or -S(O) x R D , or -C(O)R D and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -S(O) x R D , or -C(O)R D and each R 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 11 and each R A are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and R B and R C each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl, -OR A , -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -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 7 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 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 11are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0317] In some embodiments, the compound of formula (II) is a compound of formula (II-d): [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 X, Y, and Z are each independently C(R 3a ), N, N(R 3c ) or S, where at least one of X, Y, and Z is N or N(R 3c ), the bonds in the ring containing X, Y, and Z may be single or double bonds, valence permitting; 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 5 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 6 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 is selected from the group consisting of one or more R 6 optionally replaced by R 3a 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 , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)OR D , or -S(O) x R D , or -C(O)R D and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -S(O) x R D , or -C(O)R D and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 11 and each R A are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and R B and R C each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl, -OR A , -C(O)NR B R C, -C(O)R D , -C(O)OR D , or -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 7 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 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 11 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0318] In some embodiments, the compound of formula (II) is a compound of formula (II-e): [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 X, Y, and Z are each independently C(R 3a ), N, N(R 3c ) or S, where at least one of X, Y, and Z is N or N(R 3c), the bonds in the ring containing X, Y, and Z may be single or double bonds, valence permitting; 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 5 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 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 6 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 is selected from the group consisting of one or more R 6 optionally replaced by R 3a is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -ORA , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)OR D , or -S(O) x R D , or -C(O)R D and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -S(O) x R D , or -C(O)R D and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 11 and each R A are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and R B and R C each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl, -OR A , -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -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 7 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 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 11are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0319] In some embodiments, the compound of formula (II) is a compound of formula (II-f): [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 U and W are each independently C or N; and X, Y, and Z are each independently C(R 3a ), N, N(R 3c ) or S, where at least one of X, Y, and Z is N or N(R 3c ), and the bonds in the rings containing U, W, X, Y, and Z may be single or double bonds, valence permitting; 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 5 and each R 1are 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 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 6 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 is selected from the group consisting of one or more R 6 optionally replaced by R 3a 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 , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)OR D , or -S(O) x R D , or -C(O)R D and R 3cis hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -S(O) x R D , or -C(O)R D and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 11 and each R A are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O)x R D and R B and R C each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl, -OR A , -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -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 7 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 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 11 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0320] In some embodiments, the compound of Formula (II) is a compound of Formula (II-g): [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 U and W are each independently C or N; and X, Y, and Z are each independently C(R 3a ), N, N(R 3c ) or S, where at least one of X, Y, and Z is N or N(R 3c ), and the bonds in the rings containing U, W, X, Y, and Z may be single or double bonds, 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 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 6 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 is selected from the group consisting of one or more R 6 optionally replaced by R 3ais hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)OR D , or -S(O) x R D , or -C(O)R D and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -S(O) x R D , or -C(O)R D and each R 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 11 and each R Aare independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and R B and R C each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl, -OR A , -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -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 7 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 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 11 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0321] In some embodiments, the compound of Formula (II) is a compound of Formula (II-h): [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 X, Y, and Z are each independently C(R 3a ), N, N(R 3c ) or S, where at least one of X, Y, and Z is N or N(R 3c ), the bonds in the ring containing X, Y, and Z may be single or double bonds, valence permitting; 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 5 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 6 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 is selected from the group consisting of one or more R 6 optionally replaced by R 3a 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 , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)OR D , or -S(O) x R D , or -C(O)R D and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -S(O) x R D , or -C(O)R D and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 11 and each R A are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and R B and R C each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl, -OR A , -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -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 7and 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 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 11 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0322] In some embodiments, the compound of formula (II) is a compound of formula (II-i): [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 X, Y, and Z are each independently C(R 3a ), N, N(R 3c ) or S, where at least one of X, Y, and Z is N or N(R 3c ), the bonds in the ring containing X, Y, and Z may be single or double bonds, valence permitting; 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 5 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 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 6 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 is selected from the group consisting of one or more R 6 optionally replaced by R 3a 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 , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)OR D , or -S(O) x R D , or -C(O)R D and R3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -S(O) x R D , or -C(O)R D and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 11 and each R A are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D, or -S(O) x R D and R B and R C each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl, -OR A , -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -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 7 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 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 11 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0323] In some embodiments, the compound of formula (II) is a compound of formula (II-j): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, and B is cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 X, Y, and Z are each independently C(R 3a ), N, N(R 3c ) or S, where at least one of X, Y, and Z is N or N(R 3c ), the bonds in the ring containing X, Y, and Z may be single or double bonds, valence permitting, and M and P are each independently C(R 2 ) 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 5 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 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 6or 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 is selected from the group consisting of one or more R 6 and each R 2 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and R 3a 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 , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)OR D , or -S(O) x R D , or -C(O)R D and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -S(O) x R D , or -C(O)R D and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 11 and each R A are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and R B and R C each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl, -OR A , -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -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 7and 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 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 11 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0324] In some embodiments, the compound of Formula (II) is a compound of Formula (II-k): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, and B is cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 X, Y, and Z are each independently C(R 3a ), N, N(R 3c ) or S, where at least one of X, Y, and Z is N or N(R 3c ), the bonds in the ring containing X, Y, and Z may be single or double bonds, valence permitting, and M and P are each independently C(R 2 ) 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 5 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 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 6 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 is selected from the group consisting of one or more R 6 and each R 2 are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR A and R 3a 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 , -NRB C(O)R D , -NO2, -C(O)NR B R C , -C(O)OR D , or -S(O) x R D , or -C(O)R D and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -S(O) x R D , or -C(O)R D and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 11and each R A are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and R B and R C each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl, -OR A , -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -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 7 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 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 11 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0325] In some embodiments, the compound of formula (II) is a compound of formula (II-l): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, and B is cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 and U and W are each independently C or N; and X, Y, and Z are each independently C(R 3a ), N, N(R 3c ) or S, where at least one of X, Y, and Z is N or N(R 3c ), and the bonds in the rings containing U, W, X, Y, and Z may be single or double bonds, valence permitting; 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 5 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 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 6 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 is selected from the group consisting of one or more R 6 optionally replaced by R 3a 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 , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)OR D , or -S(O) x R D , or -C(O)R D and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -S(O) x R D , or -C(O)R D and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 11 and each R A are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and R B and R C each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl, -OR A , -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D or R B and R Ctogether with the atoms to which they are attached form one or more R 7 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 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 11 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0326] In some embodiments, the compound of formula (II) is a compound of formula (II-m): [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, and B is cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is selected from the group consisting of one or more R 1 and U and W are each independently C or N; and X, Y, and Z are each independently C(R 3a ), N, N(R 3c ) or S, where at least one of X, Y, and Z is N or N(R 3c ), and the bonds in the rings containing U, W, X, Y, and Z may be single or double bonds, valence permitting; L 1 and L 2 each independently represents absence, C-C-alkylene, C-C-heteroalkylene, —O—, —C(O)—, —N(R4 )-, -N(R 4 )C(O)-, or -C(O)N(R 4 )-, where each alkylene and heteroalkylene is selected from one or more R 5 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 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 6 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 is selected from the group consisting of one or more R 6 optionally replaced by R 3a 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 , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)OR D, or -S(O) x R D , or -C(O)R D and R 3c is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR A , -S(O) x R D , or -C(O)R D and each R 4 are independently hydrogen, C-C-alkyl, or C-C-haloalkyl, and each R 5 are independently hydrogen, 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 6 are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R 11 and each R Aare independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, -C(O)R D , or -S(O) x R D and R B and R C each independently represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl, -OR A , -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -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 7 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 7 is C1-C6-alkyl, halo, cyano, oxo, or -OR A1 and each R 11 are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and each R A1 is hydrogen or C1-C6-alkyl and x is 0, 1 or 2.

[0327] In some embodiments, the compound of formula (II) is selected from the compounds in Table 2, or a pharmaceutically acceptable salt thereof. [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4] [Table 2-5] [Table 2-6] [Table 2-7] [Table 2-8] [Table 2-9] [Table 2-10] [Table 2-11] [Table 2-12] [Table 2-13] [Table 2-14] [Table 2-15] [Table 2-16] [Table 2-17] [Table 2-18] [Table 2-19] [Table 2-20] [Table 2-21] [Table 2-22] [Table 2-23]

[0328] Pharmaceutical Compositions, Kits, and Administration The present invention provides pharmaceutical compositions comprising a compound of Formula (I) or (II), for example, a compound of Formula (I) or (II) described herein or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer, and optionally a pharmaceutically acceptable excipient. In certain embodiments, the pharmaceutical compositions described herein comprise a compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof and, optionally, a pharmaceutically acceptable excipient. In certain embodiments, the compound of Formula (I) or (II) or a pharmaceutically acceptable salt thereof, solvate, hydrate, tautomer, or stereoisomer thereof is provided in an effective amount in the pharmaceutical composition. In certain embodiments, the effective amount is a therapeutically effective amount. In certain embodiments, the effective amount is a prophylactically effective amount.

[0329] The pharmaceutical compositions described herein can be prepared by any method known in the art of pharmacology. In general, such preparative methods include the step of bringing into association a compound of Formula (I) or (II) (the "active ingredient") with the carrier and / or one or more other accessory ingredients, and then, if necessary and / or desired, shaping and / or packaging the product into the desired single or multi-dose unit.

[0330] Pharmaceutical compositions can be prepared, packaged, and / or sold in bulk, as a single unit dose, and / or as a plurality of single unit doses. As used herein, a "unit dose" is a discrete amount of a pharmaceutical composition containing a predetermined amount of an active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient that would be administered to a subject and / or a convenient fraction of such a dosage, for example, one-half or one-third of such a dosage.

[0331] The relative amounts of active ingredient, pharmaceutically acceptable excipient, and / or any additional ingredients in a pharmaceutical composition of the invention will vary depending on the characteristics, size, and / or condition of the subject being treated, as well as the route by which the composition is administered. By way of example, the composition may contain from 0.1% to 100% (w / w) active ingredient.

[0332] The term "pharmaceutically acceptable excipient" refers to a non-toxic carrier, adjuvant, diluent, or vehicle that does not destroy the pharmacological activity of the compound being formulated. Pharmaceutically acceptable excipients useful in preparing the pharmaceutical compositions of the present invention are any of those well known in the art of pharmaceutical formulation, including inert diluents, dispersing and / or granulating agents, surfactants and / or emulsifying agents, disintegrating agents, binders, preservatives, buffers, lubricants, and / or oils. Pharmaceutically acceptable excipients useful in preparing pharmaceutical compositions of the present invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins such as human serum albumin, buffers such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulosic substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol, and wool fat.

[0333] Compositions of the present invention can be administered orally, parenterally (including subcutaneously, intramuscularly, intravenously, and intradermally), by inhalation spray, topically, rectally, nasally, buccally, vaginally, or via an implanted reservoir. In some embodiments, provided compounds or compositions are administrable intravenously and / or orally.

[0334] The term "parenteral" as used herein includes subcutaneous, intravenous, intramuscular, intraocular, intravitreal, intraarticular, intrasynovial, intrasternal, intrathecal, intrahepatic, intraperitoneal, intralesional, and intracranial injection or infusion techniques. Preferably, the compositions are administered orally, subcutaneously, intraperitoneally, or intravenously. Sterile injectable forms of the compositions of the present invention may be aqueous or oily suspensions. These suspensions may be formulated using suitable dispersing or wetting agents and suspending agents according to techniques known in the art. Sterile injectable preparations may also be sterile injectable solutions or suspensions in non-toxic parenterally acceptable diluents or solvents, such as 1,3-butanediol solutions. Acceptable vehicles and solvents that can be used include water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are commonly used as solvents or suspending media.

[0335] The pharmaceutically acceptable compositions of the present invention can be orally administered in any orally acceptable dosage form, including, but not limited to, capsules, tablets, aqueous suspensions, or solutions. For tablets for oral use, commonly used carriers include lactose and cornstarch. Lubricants, such as magnesium stearate, are also typically added. For oral administration in capsule form, useful diluents include lactose and dried cornstarch. When an oral aqueous suspension is required, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening, flavoring, or coloring agents may also be added. In some embodiments, the provided oral formulations are formulated for immediate release or sustained / delayed release. In some embodiments, the compositions are suitable for buccal or sublingual administration, including tablets, lozenges, and pastilles. The provided compounds may also be in microencapsulated form.

[0336] Alternatively, the pharmaceutically acceptable compositions of the present invention can be administered in the form of suppositories for rectal administration.The pharmaceutically acceptable compositions of the present invention can be administered topically, especially when the target of treatment includes areas or organs that are easily accessible by topical application, including diseases of the eye, skin, or lower intestinal tract.Suitable topical formulations can be easily prepared for each of these areas or organs.

[0337] For ophthalmic use, provided pharmaceutically acceptable compositions may be formulated as a micronized suspension or in an ointment such as petrolatum.

[0338] In order to prolong the effect of a drug, it is often desirable to delay the absorption of the drug from subcutaneous or intramuscular injection.This can be achieved by using a liquid suspension of crystalline or amorphous material with poor water solubility.The absorption rate of the drug then depends on its dissolution rate, which may depend on crystal size and crystalline form.Alternatively, delayed absorption of parenterally administered drug forms can be achieved by dissolving or suspending the drug in an oil vehicle.

[0339] While the description of pharmaceutical compositions provided herein is primarily directed to pharmaceutical compositions suitable for administration to humans, those skilled in the art will understand that such compositions are generally suitable for administration to animals of all kinds. Modifications of pharmaceutical compositions suitable for administration to humans to make them suitable for administration to a variety of animals are well understood, and an ordinarily skilled veterinary pharmacologist can design and / or perform such modifications with routine experimentation.

[0340] The compound provided herein is typically formulated in unit dosage form, for example, single unit dosage form, for ease of administration and uniformity of dosage.However, it will be understood that the total daily use amount of the composition of the present invention can be determined by the attending physician within the scope of sound medical judgment.The specific therapeutically effective dose level for any specific subject or organism is determined according to various factors, including the severity of the disease and disorder being treated; the activity of the specific active ingredient being used; the specific composition being used; the age, weight, general health condition, sex and diet of the subject; the administration time, administration route and excretion rate of the specific active ingredient being used; the duration of treatment; the drugs used in combination with or simultaneously with the specific active ingredient being used; and similar factors well known in the medical field.

[0341] The exact amount of compound required to achieve an effective dose will vary from subject to subject, depending, for example, on the subject's species, age, and general condition, the severity of any side effects or disorders, the characteristics of the particular compound(s), the mode of administration, etc. The desired dose can be delivered three times a day, twice a day, once a day, every other day, every third day, weekly, every two weeks, every three weeks, or every four weeks. In certain embodiments, the desired dose can be delivered using multiple administrations (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or more administrations).

[0342] In certain embodiments, an effective amount of a compound when administered one or more times per day to a 70 kg adult human may contain from about 0.0001 mg to about 3000 mg, about 0.0001 mg to about 2000 mg, about 0.0001 mg to about 1000 mg, about 0.001 mg to about 1000 mg, about 0.01 mg to about 1000 mg, about 0.1 mg to about 1000 mg, about 1 mg to about 1000 mg, about 1 mg to about 100 mg, about 10 mg to about 1000 mg, or about 100 mg to about 1000 mg of the compound per unit dosage form.

[0343] In certain embodiments, the compound of Formula (I) or (II) may be administered at a dosage level sufficient to deliver from about 0.001 mg / kg to about 100 mg / kg, about 0.01 mg / kg to about 50 mg / kg, preferably about 0.1 mg / kg to about 40 mg / kg, preferably about 0.5 mg / kg to about 30 mg / kg, about 0.01 mg / kg to about 10 mg / kg, about 0.1 mg / kg to about 10 mg / kg, more preferably about 1 mg / kg to about 25 mg / kg of body weight per day, one or more times daily, to achieve the desired therapeutic effect.

[0344] It will be understood that the dosage ranges described herein provide guidance for administering the provided pharmaceutical compositions to adults. For example, the amount administered to a child or adolescent can be determined by a physician or person skilled in the art and may be lower than or the same as the amount administered to an adult.

[0345] It will also be understood that the compounds or compositions described herein can be administered in combination with one or more additional drugs. The compounds or compositions can be administered in combination with additional drugs that improve their bioavailability, reduce and / or alter their metabolism, inhibit their excretion, and / or alter their biodistribution. It will also be understood that the treatments employed can achieve desired effects and / or different effects on the same disorder.

[0346] The compound or composition can be administered simultaneously with, before, or after one or more additional agents that may be useful, for example, as a combination therapy. Agents include therapeutically active agents. Agents also include prophylactically active agents. Each additional agent can be administered at a dose and / or time schedule determined for that agent. The additional agents can also be administered together with each other and / or with the compounds or compositions described herein in a single dose, or separately in different doses. The particular combination employed in a regimen will take into consideration compatibility of the compounds of the invention with the additional agents and / or the desired therapeutic and / or prophylactic effect to be achieved. In general, it is expected that additional agents utilized in combination will be utilized at levels that do not exceed the levels at which they are utilized individually. In some embodiments, the levels utilized in combination will be lower than the levels utilized individually.

[0347] Exemplary additional agents include, but are not limited to, antiproliferative agents, anticancer agents, antidiabetic agents, anti-inflammatory agents, immunosuppressants, and analgesics. Agents include small organic molecules, such as drug compounds (e.g., compounds approved by the U.S. Food and Drug Administration and listed in the Code of Federal Regulations (CFR)), peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNA, RNA, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, lipids, hormones, vitamins, and cells.

[0348] Kits (e.g., pharmaceutical packs) are also encompassed by the present invention. The kits of the present invention may be useful, for example, for preventing and / or treating a proliferative or non-proliferative disease described herein. The provided kits may include a pharmaceutical composition or compound of the present invention and a container (e.g., a vial, an ampoule, a bottle, a syringe, and / or a dispenser package, or other suitable container). In some embodiments, the provided kits may optionally further include a second container containing a pharmaceutical excipient for diluting or suspending the phar...

Claims

1. Compounds of formula (I): 【Chemical 1】 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 optionally replaced by X, Y, and Z are each independently C(R ３ａ ), C(R ３ａ ) (R ３ｂ ), N, N(R ３ｃ ), or O, wherein at least one of X, Y, and Z is N, N(R ３ｃ ), or O, and the bonds in the ring containing X, Y, and Z can be single or double bonds, valence permitting; 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 ５ 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, C １ -C ６ Heteroalkylene-aryl, heteroaryl, C １ -C ６ Alkylene-heteroaryl, C １ -C ６ Heteroalkylene-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 ６ 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 the group consisting of one or more R ６ 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, -OR Ａ , -NR Ｂ R Ｃ , -C(O)R Ｄ , or —C(O)OR Ｄ and R ３ａ and R ３ｂ 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, -OR Ａ , -NR Ｂ R Ｃ , -C(O)R Ｄ , or -C(O)OR Ｄ or R ３ａ and R ３ｂ together with the carbon atom to which they are attached form an oxo group, R ３ｃ 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, C １ -C ６ Alkylene-cycloalkyl, heterocyclyl, C １ -C ６ Alkylene-heterocyclyl, aryl, C １ -C ６ Alkylene-aryl, heteroaryl, C １ -C ６ alkylene-heteroaryl, or —C(O)R Ｄ and each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R ８ optionally replaced by Each R ４ are independently hydrogen, C １ -C ６ -Alkyl, C １ -C ６ -heteroalkyl, or C １ -C ６ -haloalkyl, Each R ５ are independently hydrogen, 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 and Each R ６ 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, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R １１ optionally replaced by Each R ７ is C １ -C ６ -alkyl, halo, cyano, oxo, or -OR Ａ１ and Each R ８ 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, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, -OR Ａ , -NR Ｂ R Ｃ , -NR Ｂ C(O)R Ｄ , -NO ２ , —C(O)NR Ｂ R Ｃ , -C(O)R Ｄ , -C(O)OR Ｄ , or -S(O) ｘ R Ｄ wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R １２ optionally replaced by Each R １１ 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 １２ 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 Haloalkyl, 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 and R Ｂ and R Ｃ each independently represents 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(O)R Ｄ , or -S(O) ｘ R Ｄ and R Ｂ and R Ｃ together with the atoms to which they are attached, form one or more R ７ 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 Ａ１ is hydrogen or C １ -C ６ - alkyl, m is 0, 1, or 2; x is 0, 1, or 2).

2. Each of A and B is independently heteroaryl or heterocyclyl, each of which is selected from one or more R １ 10. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, optionally substituted with:

3. One of A and B is 【Chemistry 2】 wherein R １ 2. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein:

4. One of A and B is 【Chemistry 10-1】 【Chemistry 10-2】 【Chemistry 10-3】 10. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, independently selected from:

5. One of A and B is 【Chemistry 17】 wherein R １ 2. The compound of claim 1, wherein:

6. One of A and B is 【Chemistry 24-1】 【Chemistry 24-2】 【Chemistry 24-3】 【Chemistry 24-4】 【Chemistry 24-5】 10. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, independently selected from:

7. L １ and L ２ one of which is independently absent, -N(R ４ )C(O)-, or -C(O)N(R ４ 2. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein:

8. At least one of X, Y, and Z is N or N(R ３ｃ 2. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein

9. X is C(R ３ａ ) (e.g., CH), and Y and Z are each independently N or N(R ３ｃ 2. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein

10. 【Catalog 31】 but, 【Chemical 32】 2. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, selected from:

11. R ３ｃ But C １ -C ６ -Alkyl, C ２ -C ６ -alkenyl, C １ -C ６ -heteroalkyl, C １ -C ６ -haloalkyl, cycloalkyl, heterocyclyl, C １ -C ６ Alkylene-heterocyclyl, aryl, C １ -C ６ Alkylene-aryl, heteroaryl, C １ -C ６ alkylene-heteroaryl, heteroaryl, where each alkyl, alkylene, alkenyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R ８ 10. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, optionally substituted with:

12. The compound of formula (I) is represented by formula (I-b): 【Chemical 36】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L １ , R ２ , R ３ｃ 10. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein , m, and subvariables thereof are as defined in claim 1.

13. A is R １ heteroaryl (e.g., bicyclic heteroaryl) optionally substituted with B is one or more R １ heterocyclyl (e.g., monocyclic heterocyclyl) optionally substituted with R ３ｃ But C １ -C ６ -Alkyl, C ２ -C ６ -alkenyl, C １ -C ６ -heteroalkyl, C １ -C ６ -haloalkyl, cycloalkyl, heterocyclyl, C １ -C ６ Alkylene-heterocyclyl, aryl, C １ -C ６ Alkylene-aryl, heteroaryl, C １ -C ６ alkylene-heteroaryl, heteroaryl, where each alkyl, alkylene, alkenyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R ８ optionally replaced by R １ and R ８ 13. The compound of claim 12, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein each of: is as defined in claim 1.

14. 2. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein the compound is selected from the compounds listed in Table 1.

15. Compound of formula (II): 【Chemistry 40】 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 optionally replaced by M and P each independently represent C(R ２ ) or N, U and W are each independently C or N; X, Y, and Z are each independently C(R ３ａ ), N, N(R ３ｃ ), O, or S, where at least one of X, Y, and Z is N or N(R ３ｃ ) wherein the bonds in the ring containing U, W, X, Y, and Z may be single or double bonds, valence permitting; 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 ５ 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, 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 ６ 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 the group consisting of one or more R ６ 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, or -OR Ａ and R ３ａ 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 , -NR Ｂ C(O)R Ｄ , -NO ２ , —C(O)NR Ｂ R Ｃ , -C(O)OR Ｄ , or -S(O) ｘ R Ｄ , or -C(O)R Ｄ and R ３ｃ 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, C １ -C ６ Alkylene-cycloalkyl, heterocyclyl, C １ -C ６ Alkylene-heterocyclyl, aryl, C １ -C ６ Alkylene-aryl, heteroaryl, C １ -C ６ alkylene-heteroaryl, or —C(O)R Ｄ and each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from the group consisting of one or more R ８ optionally replaced by Each R ４ are independently hydrogen, C １ -C ６ -Alkyl, C １ -C ６ -heteroalkyl, or C １ -C ６ -haloalkyl, Each R ５ are independently hydrogen, 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 and Each R ６ 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, 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, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is selected from one or more R １１ optionally replaced by 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, 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 R Ｂ and R Ｃ each independently represents 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, -OR Ａ , —C(O)NR Ｂ R Ｃ , -C(O)R Ｄ , -C(O)OR Ｄ , or -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 ７ 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 ７ is C １ -C ６ -alkyl, halo, cyano, oxo, or -OR Ａ１ and Each R １１ 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 Ａ１ is hydrogen or C １ -C ６ - alkyl, x is 0, 1, or 2).

16. Each of A and B is independently heteroaryl or heterocyclyl, each of which is selected from one or more R １ 16. The compound of claim 15, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, optionally substituted with:

17. One of A and B is 【Chemistry 41】 wherein R １ 16. The compound of claim 15, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein:

18. One of A and B is 【Chemistry 49】 16. The compound of claim 15, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, independently selected from:

19. One of A and B independently contains one or more R １ 16. The compound of claim 15, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein R is a nitrogen-containing heterocyclyl optionally substituted with R.

20. One of A and B is 【Chemical 56】 wherein R １ 16. The compound of claim 15, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein:

21. One of A and B is 【Hua 63-1】 【Hua 63-2】 16. The compound of claim 15, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, independently selected from:

22. B, 【Chemistry 68】 16. The compound of claim 15, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, selected from:

23. L １ is —C(O)NH—, and L ２ 16. The compound of claim 15, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein is absent.

24. Each of M and P is independently C(R ２ 16. The compound of claim 15, wherein R is 1 or 2 (e.g., CH), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

25. 16. The compound of claim 15, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein each of U and W is independently C.

26. 16. The compound of claim 15, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein U is C and W is N.

27. Two of X, Y, and Z are independently N or N(R ３ｃ 16. The compound of claim 15, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein:

28. 【Catalog 70】 but, 【Chemical Formula 71】 16. The compound of claim 15, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, selected from:

29. The compound of formula (II) is represented by formula (II-c): 【Chemical 73】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, M, P, X, Y, Z, and each of its subvariables are as defined in claim 15, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

30. 16. The compound of claim 15, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein the compound is selected from any one of the compounds shown in Table 2.

31. A pharmaceutical composition comprising a compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, and a pharmaceutically acceptable excipient.

32. The compound is (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); and / or (iii) stabilizes a target nucleic acid (e.g., RNA, e.g., pre-mRNA); 31. A compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or a pharmaceutical composition comprising said compound and a pharmaceutically acceptable excipient.

33. The compound is (i) increases splicing at a splice site on a target nucleic acid (e.g., an RNA, e.g., a pre-mRNA) by about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or more, as determined, for example, by qPCR; or (ii) reduces splicing at a splice site on a target nucleic acid (e.g., an RNA, e.g., a pre-mRNA) by about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or more, as determined, for example, by qPCR; 31. A compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or a pharmaceutical composition comprising said compound and a pharmaceutically acceptable excipient.

34. 31. A method of forming a complex comprising a component of a spliceosome (e.g., a major spliceosome component or a minor spliceosome component), a nucleic acid (e.g., DNA, RNA, e.g., pre-mRNA), and a compound of formula (I) or (II) according to any one of claims 1 to 30, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or a composition comprising said compound, comprising: The method comprising contacting the nucleic acid (eg, DNA, RNA, eg, pre-mRNA) with a compound of formula (I) or (II).

35. 31. A method for modifying the conformation of a nucleic acid (e.g., DNA, RNA, e.g., pre-mRNA), comprising contacting the nucleic acid with a compound of formula (I) or (II) according to any one of claims 1 to 30, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or a pharmaceutical composition comprising said compound and a pharmaceutically acceptable excipient.

36. The modification is (i) forming a bulge in the nucleic acid; (ii) stabilizing the bulge of the nucleic acid; and / or (iii) reducing the bulge of the nucleic acid; 36. The method of claim 35.

37. A composition comprising a compound of formula (I) or (II) according to any one of claims 1 to 30, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or a pharmaceutical composition comprising said compound and a pharmaceutically acceptable excipient, for treating a disease or disorder in a subject.

38. 38. The composition or pharmaceutical composition of claim 37, wherein the disease or disorder comprises a proliferative disease (e.g., cancer, benign neoplasm, or angiogenesis); or 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 renal disease or disorder, or an infectious disease.

Images