Compounds and methods for adjusting splicing

Abstract

The present disclosure features, among other things, compounds and related compositions that modulate nucleic acid splicing, eg, pre-mRNA splicing, and methods of their use.

Description

[Technical Field]

[0001] Priority Claim This application claims priority to U.S. Patent Application No. 63 / 007,331, filed on 8 April 2020; U.S. Patent Application No. 63 / 044,318, filed on 25 June 2020; U.S. Patent Application No. 63 / 072,922, filed on 31 August 2020; and U.S. Patent Application No. 63 / 126,494, filed on 16 December 2020. The disclosures of each of the above applications are incorporated in their entirety by reference herein. [Background technology]

[0002] Alternative splicing is a major cause of protein diversity in higher eukaryotes and is frequently regulated in tissue-specific or developmental stage-specific ways. Disease-associated alternative splicing patterns in premRNA often map to changes in splice site signaling or sequence motifs and regulatory splicing factors (Faustino and Cooper (2003), Genes Dev 17(4):419-37). Current therapies modulating RNA expression involve oligonucleotide targeting and gene therapy. However, each of these modalities presents unique challenges, as currently observed. Therefore, novel techniques for modulating 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 [Overview of the project] [Means for solving the problem]

[0004] This disclosure features, in particular, compounds and related compositions for modulating nucleic acid splicing, such as premRNA splicing, and methods of using the same. In one embodiment, the compounds described herein are compounds of formula (I), (III), or (V), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers thereof. The disclosure further provides, for example, compounds of formula (I), (III), or (V), and their pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, and compositions thereof, which target nucleic acids (e.g., premRNA, or nuclear small ribonucleoproteins (snRNPs) or nucleic acid components of spliceosomes), proteins (e.g., snRNPs or protein components of spliceosomes, e.g., members of splicing mechanisms, e.g., one or more of U1, U2, U4, U5, U6, U11, U12, U4atac, U6atac snRNPs), or combinations thereof, and which, in embodiments, bind to or form complexes with them, the compounds of the disclosure (e.g., compounds of formula (I), (III), or (V), and their pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers), and methods of using the same. In another embodiment, the compounds described herein may be used to alter the composition or structure of nucleic acids (e.g., premRNA or mRNA (e.g., premRNA and mRNA derived from premRNA)) by increasing or decreasing splicing at splice sites, for example. In some embodiments, increasing or decreasing splicing results in adjustment of the level of gene products (e.g., RNA or protein) produced. In another embodiment, the compounds described herein may be used for the prevention and / or treatment of diseases, disorders or conditions, such as splicing, such as alternative splicing. In some embodiments, the compounds described herein (e.g., compounds of formula (I), (III), or (V), and their pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers) and compositions thereof are used for the prevention and / or treatment of proliferative disorders, disorders or conditions in a subject (e.g., diseases, disorders or conditions characterized by unwanted cell proliferation, such as cancer or benign neoplasms). In some embodiments, the compounds described herein (e.g., compounds of formula (I), (III), or (V), and their pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers) and compositions thereof are used for the prevention and / or treatment of nonproliferative disorders or conditions. In some embodiments, the compounds described herein (e.g., compounds of formula (I), (III), or (V), and their pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers) and compositions thereof are used for the prevention and / or treatment of neurological disorders or disorders, autoimmune disorders or disorders, immunodeficiency disorders or disorders, lysosomal storage disorders or disorders, cardiovascular disorders or disorders, metabolic disorders or disorders, respiratory disorders or disorders, renal disorders or disorders, or infections in a subject.

[0005] In one embodiment, the present disclosure relates to a compound of formula (I). [ka] Or provide a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, where A, B, L 1 , L 2 W, X, Y, Z, R 2 Each of the subvariables, and their respective subvariables, is defined as described herein.

[0006] In another embodiment, the present disclosure relates to a compound of formula (III). [Chemical formula] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, B, L 1 , L 2 , X, Y, Z, R 2 , R 7a , R 7b , and each of its sub-variables is defined as described herein.

[0007] In another aspect, the present disclosure provides a compound of formula (V) [Chemical formula] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A, R B , L 1 , L 2 , Y, R 2 , R 3 , m, n, and each of its sub-variables is defined as described herein.

[0008] In another aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I), (III), or (V), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, and optionally a pharmaceutically acceptable additive. In one embodiment, the pharmaceutical composition described herein comprises an effective amount (e.g., a therapeutically effective amount) of a compound of formula (I), (III), or (V), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0009] In another embodiment, the Disclosure provides a method for preparing splicing, for example, the splicing of nucleic acids (e.g., DNA or RNA, e.g., premRNA), by a compound of formula (I), (III), or (V), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another embodiment, the Disclosure provides a composition for use in preparing splicing, for example, the splicing of nucleic acids (e.g., DNA or RNA, e.g., premRNA), by a compound of formula (I), (III), or (V), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. Preparation of splicing may include affecting any step involved in splicing, and may include events upstream or downstream of the splicing event. For example, in some embodiments, the compounds of formula (I), (III), or (V) bind to a target, such as a target nucleic acid (e.g., DNA or RNA, e.g., RNA precursor, e.g., premRNA), a target protein, or a combination thereof (e.g., snRNP and premRNA). The target may include premRNA or components of a splicing mechanism, such as a splice site in U1snRNP. In some embodiments, the compounds of formula (I), (III), or (V) alter a target nucleic acid (e.g., DNA or RNA, e.g., RNA precursor, e.g., premRNA), a target protein, or a combination thereof. In some embodiments, the compounds of formula (I), (III), or (V) increase or decrease splicing at splice sites on target nucleic acids (e.g., RNA, e.g., RNA precursors, e.g., premRNA) by about 0.5% or more (e.g., about 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 90%, 95%, or more) compared to a reference (e.g., the absence of the compounds of formula (I), (III), or (V) in normal or abnormal cells or tissues).In some embodiments, the presence of a compound of formula (I), (III), or (V) results in an increase or decrease of approximately 0.5% or more (e.g., approximately 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 90%, 95%, or more) in the transcription of the target nucleic acid (e.g., RNA) compared to a reference (e.g., the absence of a compound of formula (I), (III), or (V) in normal or abnormal cells or tissues).

[0010] In another embodiment, the Disclosure provides methods for preventing and / or treating a disease, disorder, or condition in a subject by administering a compound of formula (I), (III), or (V), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or a related composition. In some embodiments, the disease or disorder causes unwanted or abnormal splicing. In some embodiments, the disease or disorder is a proliferative disorder, disorder, or condition. Exemplary proliferative disorders include cancer, benign neoplasms, or angiogenesis. In other embodiments, the Disclosure provides methods for treating and / or preventing nonproliferative disorders, disorders, or conditions. In yet another embodiment, the Disclosure provides methods for treating and / or preventing neurological disorders, autoimmune disorders, immunodeficiency disorders, lysosomal storage disorders, cardiovascular disorders, metabolic disorders, respiratory disorders, kidney disorders, or infections.

[0011] In another embodiment, the Disclosure provides a method for downregulating the expression (e.g., the level or rate of production) of a target protein in a biological sample or subject using a compound of formula (I), (III), or (V), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another embodiment, the Disclosure provides a method for upregulating the expression (e.g., the level or rate of production) of a target protein in a biological sample or subject using a compound of formula (I), (III), or (V), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another embodiment, the Disclosure provides a method for altering the isoform of a target protein in a biological sample or subject using a compound of formula (I), (III), or (V), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. Another aspect of the Disclosure relates to a method for inhibiting the activity of a target protein in a biological sample or subject. In some embodiments, administration of a compound of formula (I), (III), or (V) to a biological sample, cell, or subject includes inhibition of cell growth or induction of cell death.

[0012] In another embodiment, the Disclosure provides compositions for use in preventing and / or treating diseases, disorders, or conditions in a subject by administering compounds of formula (I), (III), or (V), or pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers thereof, or related compositions. In some embodiments, the disease or disorder causes unwanted or abnormal splicing. In some embodiments, the disease or disorder is a proliferative disorder, disorder, or condition. Exemplary proliferative disorders include cancer, benign neoplasms, or angiogenesis. In other embodiments, the Disclosure provides methods for treating and / or preventing nonproliferative diseases, disorders, or conditions. In yet another embodiment, the Disclosure provides compositions for use in treating and / or preventing neurological disorders, autoimmune disorders, immunodeficiency disorders, lysosomal storage disorders, cardiovascular disorders, metabolic disorders, respiratory disorders, kidney disorders, or infections.

[0013] In another embodiment, the Disclosure provides compositions for use in a biological sample or subject to downcontrol the expression (e.g., level or rate of production) of a target protein by a compound of formula (I), (III), or (V), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another embodiment, the Disclosure provides compositions for use in a biological sample or subject to upcontrol the expression (e.g., level or rate of production) of a target protein by a compound of formula (I), (III), or (V), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. In another embodiment, the Disclosure provides compositions for use in a biological sample or subject to alter the isoform of a target protein by a compound of formula (I), (III), or (V), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof. Another aspect of this disclosure relates to compositions for use in inhibiting the activity of a target protein in a biological sample or subject. In some embodiments, administration of a compound of formula (I), (III), or (V) to a biological sample, cell, or subject includes inhibition of cell growth or induction of cell death.

[0014] In another embodiment, the Disclosure features a kit comprising a container having a compound of formula (I), (III), or (V), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or pharmaceutical composition thereof. In certain embodiments, the kit described herein further comprises instructions for administering a compound of formula (I), (III), or (V), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or pharmaceutical composition thereof.

[0015] In all aspects of this disclosure, in some embodiments, the compounds, target nucleic acids (e.g., DNA, RNA, e.g., premRNA), or target proteins described herein are as specified in U.S. Patent No. 8,729,263, U.S. Patent Application Publication No. 2015 / 0005289, International Publication No. 2014 / 028459, International Publication No. 2016 / 128343, International Publication No. 2016 / 196386, International Publication No. 2017 / 100726, and International Publication No. 2018 / 23 Compounds other than those described in one of the following brochures: 2039, International Publication No. 2018 / 098446, International Publication No. 2019 / 028440, International Publication No. 2019 / 060917, International Publication No. 2019 / 199972, and International Publication No. 2020 / 004594, target nucleic acids (e.g., DNA, RNA, e.g., premRNA), or target proteins, target nucleic acids (e.g., DNA, RNA, e.g., premRNA), or target proteins. In some embodiments, the compounds, target nucleic acids (e.g., DNA, RNA, e.g., premRNA), or target proteins described herein are incorporated herein by reference in their entirety in U.S. Patent No. 8,729,263, U.S. Patent Application Publication No. 2015 / 0005289, International Publication No. 2014 / 028459, International Publication No. 2016 / 128343, International Publication No. 2016 / 196386, and International Publication No. 2 The compounds, target nucleic acids (e.g., DNA, RNA, e.g., premRNA), or target proteins described in one of the following pamphlets: 017 / 100726, International Publication No. 2018 / 232039, International Publication No. 2018 / 098446, International Publication No. 2019 / 028440, International Publication No. 2019 / 060917, International Publication No. 2019 / 199972, and International Publication No. 2020 / 004594.

[0016] Details of one or more embodiments of the present invention are described herein. Other features, purposes, and advantages of the present invention will become apparent from the detailed description, examples, and claims. [Modes for carrying out the invention]

[0017] Selected definition of chemistry Definitions of specific functional groups and chemical terms are described in more detail below. Chemical elements are based on the periodic table, CAS version, and Handbook of Chemistry and Physics, 75. th Identified according to the ed. and inside cover, specific functional groups are generally defined as described therein. Furthermore, general principles of organic chemistry, as well as specific functional group moieties and reactivity, are as follows: 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 This information is found in Edition, Cambridge University Press, Cambridge, 1987.

[0018] Abbreviations used herein have their usual meanings in the arts of chemistry and biology. Chemical structures and formulas described herein are constructed in accordance with standard rules of chemical valence known in the art of chemistry.

[0019] When a range of values ​​is listed, it is intended to include each value and subrange within that 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.

[0020] The following terms are intended to have the meanings presented below and are useful in understanding the description and intended scope of the present invention.

[0021] In this specification, "alkyl" refers to a linear or branched saturated hydrocarbon group having 1 to 24 carbon atoms ("C1-C24"). 24 Alkyl). In some embodiments, the alkyl group has 1 to 12 carbon atoms ("C1-C12"). 12("Alkyl"). In some embodiments, the alkyl group has 1 to 8 carbon atoms ("C1-C8 alkyl"). In some embodiments, the alkyl group has 1 to 6 carbon atoms ("C1-C6 alkyl"). In some embodiments, the alkyl group has 2 to 6 carbon atoms ("C2-C6 alkyl"). In some embodiments, the 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), iso-butyl (C4), n-pentyl (C5), 3-pentanyl (C5), amyl (C5), neopentyl (C5), 3-methyl-2-butanyl (C5), tertiary amyl (C5), and n-hexyl (C6). Further examples of alkyl groups include n-heptyl (C7), n-octyl (C8), and the like. Each alkyl group entity may independently be optionally substituted, i.e., unsubstituted ("unsubstituted alkyl"), or substituted with one or more substituents, e.g., 1 to 5 substituents, 1 to 3 substituents, or 1 substituent ("substituted alkyl"). In certain embodiments, the alkyl group is unsubstituted C1-C 10 The alkyl group is an alkyl group (e.g., -CH3). In certain embodiments, the alkyl group is a substituted C1-C6 alkyl group.

[0022] As used herein, "alkenyl" refers to a linear or branched hydrocarbon group having 2 to 24 carbon atoms, one or more carbon-carbon double bonds, and zero triple bonds. 24 ("Alkenyl"). In some embodiments, the alkenyl group has 2 to 10 carbon atoms ("C2-C10"). 10("Alkenyl"). In some embodiments, the alkenyl group has 2 to 8 carbon atoms ("C2-C8 alkenyl"). In some embodiments, the alkenyl group has 2 to 6 carbon atoms ("C2-C6 alkenyl"). In some embodiments, the alkenyl group has 2 carbon atoms ("C2 alkenyl"). One or more carbon-carbon double bonds may be internal (e.g., in 2-butenyl) or terminal (e.g., in 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), etc. Examples of C2-C6 alkenyl groups include the above C2-C4 alkenyl groups, as well as pentenyl (C5), pentadienyl (C5), hexenyl (C6), etc. Further examples of alkenyls include heptenyl (C7), octenyl (C8), octatrienyl (C8), and the like. Each entity of an alkenyl group may independently be optionally substituted, i.e., unsubstituted ("unsubstituted alkenyl") or substituted with one or more substituents, e.g., 1 to 5 substituents, 1 to 3 substituents, or 1 substituent ("substituted alkenyl"). In certain embodiments, the alkenyl group is unsubstituted C1-C 10 It is an alkenyl. In certain embodiments, the alkenyl group is a substituted C2-C6 alkenyl.

[0023] As used herein, the term "alkynyl" refers to a linear or branched hydrocarbon group having 2 to 24 carbon atoms and one or more carbon-carbon triple bonds. 24 Alkenyl). In some embodiments, the alkynyl group has 2 to 10 carbon atoms ("C2-C10"). 10("Alkynyl"). In some embodiments, the alkynyl group has 2 to 8 carbon atoms ("C2-C8 alkynyl"). In some embodiments, the alkynyl group has 2 to 6 carbon atoms ("C2-C6 alkynyl"). In some embodiments, the alkynyl group has 2 carbon atoms ("C2 alkynyl"). One or more carbon-carbon triple bonds may be internal (e.g., in 2-butynyl) or terminal (e.g., in 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 entity of the alkynyl group may independently be optionally substituted, i.e., unsubstituted ("unsubstituted alkynyl"), or substituted with one or more substituents, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent ("substituted alkynyl"). In certain embodiments, the alkynyl group is unsubstituted C2~ 10 It is an alkynyl group. In certain embodiments, the alkynyl group is a substituted C2-6 alkynyl group.

[0024] As used herein, the term "haloalkyl" refers to a cyclic, stable linear or branched chain, or a combination thereof, comprising at least one carbon atom and at least one halogen selected from the group consisting of F, Cl, Br, and I. The halogens F, Cl, Br, and I can be positioned at any position within the haloalkyl group. Exemplary haloalkyl groups include, but are not limited to, -CF3, -CCl3, -CH2-CF3, -CH2-CCl3, -CH2-CBr3, and -CH2-Cl3. 3、 This includes -CH2-CH2-CH(CF3)-CH3, -CH2-CH2-CH(Br)-CH3, and -CH2-CH=CH-CH2-CF3. Each example of a haloalkyl group may independently be optionally substituted, i.e., unsubstituted ("unsubstituted haloalkyl") or substituted with one or more substituents, e.g., 1 to 5 substituents, 1 to 3 substituents, or 1 substituent ("substituted haloalkyl").

[0025] As used herein, the term "heteroalkyl" means an acyclic, stable linear or branched chain, or combination thereof, comprising at least one carbon atom and at least one heteroatom selected from the group consisting of O, N, P, Si, and S, wherein the nitrogen and sulfur atoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized. The heteroatoms O, N, P, S, and Si can be positioned at any position in 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)2-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, for example, -CH2-NH-OCH3 and -CH2-O-Si(CH3)3. The term "heteroalkyl" is listed, followed by a list of specific heteroalkyl groups, for example, -CH2O, -NR C R D In cases such as heteroalkyl and -CH2O or -NR C R D It is understood that the terms are non-duplication or non-mutually exclusive. Rather, specific heteroalkyl groups are listed for clarity. Thus, the term "heteroalkyl" in this specification refers to specific heteroalkyl groups, e.g., -CH2O, -NR C R D It should not be interpreted as excluding such examples. Each heteroalkyl entity may independently be optionally substituted, that is, it may be unsubstituted ("unsubstituted heteroalkyl") or substituted with one or more substituents, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent ("substituted heteroalkyl").

[0026] As used herein, "aryl" refers to a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 π electrons shared in a cyclic arrangement) having 6 to 14 ring carbon atoms and 0 heteroatoms provided in an aromatic ring system ("C6~C 14 In some embodiments, the aryl group has six ring carbon atoms ("C6 aryl"; e.g., phenyl). In some embodiments, the aryl group has ten ring carbon atoms ("C6 aryl"). 10 "Aryl"; for example, naphthyl, e.g., 1-naphthyl and 2-naphthyl). In some embodiments, the aryl group has 14 ring carbon atoms ("C"). 14 "Aryl" (e.g., anthracyl). Aryl groups are, for example, C6~C 10 It may also be written as a member aryl, where the term "member" refers to a non-hydrogen ring atom within the part. The aryl group includes phenyl, naphthyl, indenyl, and tetrahydronaphthyl. Each entity of the aryl group may independently be optionally substituted, i.e., unsubstituted ("unsubstituted aryl") or substituted with one or more substituents ("substituted aryl"). In certain embodiments, the aryl group is an unsubstituted C6-C 14 It is aryl. In certain embodiments, the aryl group is substituted C6~C 14 It is Ariel.

[0027] As used herein, “heteroaryl” refers to a 5- to 10-membered monocyclic or bicyclic 4n+2 aromatic ring system (e.g., having 6 or 10 π electrons shared in the cyclic arrangement) having a ring carbon atom and 1 to 4 ring heteroatoms (where each heteroatom is independently selected from nitrogen, oxygen, and sulfur) provided in the aromatic ring system (“5- to 10-membered heteroaryl”). In heteroaryl groups containing one or more nitrogen atoms, the attachment site may be a carbon or nitrogen atom, as the valence allows. A heteroaryl bicyclic ring system 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 with one or more aryl groups, where the attachment site is on the aryl or heteroaryl ring, and in such cases, the number of ring members indicates the number of ring members in the fused (aryl / heteroaryl) ring system. In a bicyclic heteroaryl group in which one ring does not contain a heteroatom (e.g., indolyl, quinolinyl, carbazolyl), the attachment site may be on either ring, i.e., a ring supporting a heteroatom (e.g., 2-indolyl) or a ring not containing a heteroatom (e.g., 5-indolyl). The heteroaryl group may also be described as, for example, a 6- to 10-membered heteroaryl, where the term "member" refers to a non-hydrogen ring atom within the part. Each entity example of the heteroaryl group may independently be optionally substituted, i.e., unsubstituted ("unsubstituted heteroaryl") or substituted with one or more substituents, e.g., 1 to 5 substituents, 1 to 3 substituents, or 1 substituent ("substituted heteroaryl").

[0028] Exemplary five-membered heteroaryl groups containing one heteroatom include, but are not limited to, pyrrolyl, furanyl, and thiophenyl. Exemplary five-membered heteroaryl groups containing two heteroatoms include, but are not limited to, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary five-membered heteroaryl groups containing three heteroatoms include, but are not limited to, triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary five-membered heteroaryl groups containing four heteroatoms include, but are not limited to, tetrazolyl. Exemplary six-membered heteroaryl groups containing one heteroatom include, but are not limited to, pyridinyl. Exemplary six-membered heteroaryl groups containing two heteroatoms include, but are not limited to, pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary six-membered heteroaryl groups containing three or four heteroatoms include, but are not limited to, triazinyl and tetradinyl, respectively. Exemplary seven-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, benzofuranil, benzoisofuranil, benzimidazolyl, benzoxazolyl, benzoisoxazolyl, benzoxadiazolyl, benzthiazolyl, benzoisothiazolyl, benzthiadiazolyl, indolidinyl, and prinyl. Exemplary 6,6-bicyclic heteroaryl groups include, but are not limited to, naphthylidinyl, pteridinyl, quinolinyl, isoquinolinyl, sinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl. Other exemplary heteroaryl groups include heme and heme derivatives.

[0029] As used herein, "cycloalkyl" refers to a non-aromatic ring system with 3 to 10 ring carbon atoms ("C3-C3"). 10This refers to a cycloalkyl group (or a non-aromatic cyclic hydrocarbon group having zero heteroatoms). In some embodiments, the cycloalkyl group has 3 to 8 ring carbon atoms ("C3-C8 cycloalkyl"). In some embodiments, the cycloalkyl group has 3 to 6 ring carbon atoms ("C3-C6 cycloalkyl"). In some embodiments, the cycloalkyl group has 3 to 6 ring carbon atoms ("C3-C6 cycloalkyl"). In some embodiments, the cycloalkyl group has 5 to 10 ring carbon atoms ("C5-C 10 Cycloalkyl groups are also referred to as, for example, C4-C7 member cycloalkyl groups, where the term "member" refers to a non-hydrogen ring atom within the group. 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), and cyclohexadienyl (C6). Examples of C3-C8 cycloalkyl groups include, but are not limited to, the above-mentioned C3-C6 cycloalkyl groups, as well as 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 others. 10 Cycloalkyl groups include, but are not limited to, the above C3-C8 cycloalkyl groups, as well as cyclononyl (C9), cyclononenyl (C9), and cyclodecyl (C9). 10 ), cyclodecenyl (C 10 ), octahydro-1H-indenyl (C9), decahydronaphthalenyl (C9) 10 ), spiro[4.5]decanil(C 10) and others are included. As illustrated by the above examples, in certain embodiments, the cycloalkyl group may be monocyclic ("monocyclic cycloalkyl") or may include fused ring systems, crosslinked ring systems or spiro-ring systems, for example, bicyclic systems ("bicyclic cycloalkyl"), and may be saturated or partially unsaturated. "Cycloalkyl" also includes ring systems in which a cycloalkyl ring as defined above is fused with one or more aryl groups, where the attachment site is on the cycloalkyl ring, and in such cases, the number of carbons still indicates the number of carbons in the cycloalkyl ring system. Each example of a cycloalkyl group may independently be optionally substituted, i.e., unsubstituted ("unsubstituted cycloalkyl") or substituted with one or more substituents ("substituted cycloalkyl"). In certain embodiments, the cycloalkyl group may be unsubstituted C3-C 10 It is a cycloalkyl group. In certain embodiments, the cycloalkyl group is a substituted C3-C3 group. 10 It is a cycloalkyl group.

[0030] "Heterocyclyl" as used herein refers to a 3- to 10-membered non-aromatic ring system having a ring carbon atom and 1 to 4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon ("3- to 10-membered heterocyclyl"). In heterocyclyl groups containing one or more nitrogen atoms, the attachment site may be a carbon or nitrogen atom, as the valence allows. Heterocyclyl groups may be monocyclic ("monocyclic heterocyclyl"), fused, bridging, or spirocyclic, for example, bicyclic ("bicyclic heterocyclyl"), and may be saturated or partially unsaturated. A heterocyclyl bicyclic ring system may 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 with one or more cycloalkyl groups (where the attachment site is on the cycloalkyl or heterocyclyl ring), or ring systems in which a heterocyclyl ring as defined above is fused with one or more aryl or heteroaryl groups (where the attachment site is on the heterocyclyl ring), in which case the number of ring members continues to indicate the number of ring members in the heterocyclyl ring system. A heterocyclyl group may also be described, for example, as a 3- to 7-membered heterocyclyl, where the term "member" refers to the non-hydrogen ring atoms in the part, i.e., carbon, nitrogen, oxygen, sulfur, boron, phosphorus, and silicon. Each example of a heterocyclyl entity 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 10-membered heterocyclyl.

[0031] Exemplary three-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azildinyl, oxyranyl, and thiorenyl. Exemplary four-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azetidinyl, oxetanyl, and thietanyl. Exemplary five-membered heterocyclyl groups containing one heteroatom include, but are not limited to, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl, and pyrrolyl-2,5-dione. Exemplary five-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, dioxolanyl, oxasulfuranil, disulfuranil, and oxazolidine-2-one. Exemplary five-membered heterocyclyl groups containing three heteroatoms include, but are not limited to, triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary six-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-methylpyridine 2-onyl), and thianyl. Exemplary six-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, piperazinyl, morpholinyl, pyridadinol (2-methylpyridazine-3-onyl), pyrimidinol (e.g., 1-methylpyrimidine-2-onyl, 3-methylpyrimidine-4-onyl), dithianyl, and dioxanyl. Exemplary six-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, triazinyl. Exemplary seven-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azepanyl, oxepanyl, and thiepanyl. Examples of eight-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azokanyl, oxekanyl, and thiokanyl.Examples of five-membered heterocyclyl groups condensed on exemplary C6 aryl rings (also referred to herein as 5,6-bicyclic heterocyclyl rings) include, but are not limited to, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, and benzoxazolinonyl. Examples of five-membered heterocyclyl groups condensed on exemplary heterocyclyl rings (also referred to herein as 5,5-bicyclic heterocyclyl rings) include, but are not limited to, octahydropyrrolopyrrolyl (e.g., octahydropyrrolo[3,4-c]pyrrolyl). Examples of six-membered heterocyclyl groups condensed on exemplary heterocyclyl rings (also referred to herein as 4,6-membered heterocyclyl rings) include, but are not limited to, diazaspirononanyl (e.g., 2,7-diazaspiron[3.5]nonanyl). Examples of six-membered heterocyclyl groups condensed on exemplary aryl rings (also referred to herein as 6,6-bicyclic heterocyclyl rings) include, but are not limited to, tetrahydroquinolinyl and tetrahydroisoquinolinyl. Examples of six-membered heterocyclyl groups condensed on exemplary cycloalkyl rings (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). Examples of six-membered heterocyclyl groups condensed on exemplary cycloalkyl rings (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).

[0032] The terms "alkylene," "alkenylene," "alkynylene," "haloalkylene," "heteroalkylene," "cycloalkylene," or "heterocyclylene," unless otherwise specified, mean a divalent group derived from alkyl, alkenyl, alkynyl, haloalkylene, heteroalkylene, cycloalkyl, or heterocyclyl, either alone or as part of another substituent. For example, the term "alkenylene," unless otherwise specified, means a divalent group derived from an alkene, either alone or as part of another substituent. Alkylene, alkenylene, alkylylene, haloalkylene, heteroalkylene, cycloalkylene, or heterocyclylene groups may also be described as, for example, C1-C6 member alkylene, C2-C6 member alkenylene, C2-C6 member alkylylene, C1-C6 member haloalkylene, C1-C6 member heteroalkylene, C3-C8 member cycloalkylene, or C3-C8 member heterocyclene, where the term "member" refers to a non-hydrogen atom within the part. In the case of heteroalkylene and heterocyclylene groups, the heteroatom can also occupy one or both of the chain ends (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, etc.). Furthermore, the orientation of the linking group is not indicated by the direction in which the formula of the linking group is written. For example, the formula -C(O)2R'- can represent both -C(O)2R'- and -R'C(O)2-.

[0033] As used herein, the terms "cyano" or "-CN" refer to substituents having a carbon atom bonded to a nitrogen atom by a triple bond, for example, C≡N.

[0034] As used herein, the terms "halogen" or "halo" refer to fluorine, chlorine, bromine, or iodine.

[0035] As used herein, the term "hydroxy" refers to -OH.

[0036] As used herein, the term "nitro" refers to a substituent having two oxygen atoms bonded to a nitrogen atom, for example, -NO2.

[0037] As used herein, the term “nucleic acid base” refers to a nitrogen-containing biocompound found to be linked to a sugar within a nucleoside (the basic structural building block of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)). The primary, or naturally occurring, nucleic acid bases 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. A, G, C, and T appear in DNA, and therefore these molecules are referred to as DNA bases; A, G, C, and U are referred to as RNA bases. Adenine and guanine belong to the biring class of molecules called purines (abbreviated as R). Cytosine, thymine, and uracil are all pyrimidines. Other nucleic acid bases that do not function as normal parts of the genetic code are referred to as non-natural. In one embodiment, the nucleic acid base may be chemically modified, for example, by alkyl (e.g., methyl), halo, -O-alkyl, or other modifications.

[0038] As used herein, the term “nucleic acid” refers to single-stranded or double-stranded deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) and their polymers. The term “nucleic acid” includes genes, cDNA, premRNA, or mRNA. In one embodiment, the nucleic acid molecule is synthetic (e.g., chemically synthesized) or recombinant. Unless explicitly limited, the term encompasses nucleic acids containing analogs or derivatives of natural nucleotides having similar binding properties to a reference nucleic acid and being metabolized in a similar manner to naturally occurring nucleotides. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses its conservatively modified variants (e.g., degenerate codon substitutions), alleles, orthologs, SNPs, and complementary sequences, as well as sequences explicitly indicated.

[0039] As used herein, "oxo" refers to the carbonyl group, i.e., -C(O)-.

[0040] symbol [ka] This refers to an attachment site to another part or functional group within the compound, as used herein with respect to the compound of formula (I).

[0041] Alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups as defined herein are optionally substituted. In general, the term “substituted” means, whether or not the term “optionally” precedes it, that at least one hydrogen present on the group (e.g., a carbon or nitrogen atom) is replaced by an acceptable substituent, e.g., a substituent that, by substitution, results in a stable compound, e.g., a compound that does not spontaneously undergo transformation by rearrangement, cyclization, elimination, or other reactions. Unless otherwise indicated, a “substituted” group has substituents at one or more substituted positions on the group, and when multiple positions in any given structure are substituted, the substituents are the same or different at each position. The term “substituted” is intended to include substitution by all acceptable substituents of an organic compound, e.g., substitution by any substituent described herein that results in the formation of a stable compound. This disclosure intends any such combination to result in a stable compound. For the purposes of the present invention, the heteroatom, for example, nitrogen, may have any suitable substituents as described herein that satisfy the valence of the hydrogen substituent and / or the heteroatom and result in the formation of a stable moiety.

[0042] Two or more substituents can optionally join to form aryl, heteroaryl, cycloalkyl, or heterocyclyl groups. Such so-called ring-forming substituents are typically, but not necessarily, found to be attached to a cyclic base structure. In one embodiment, the ring-forming substituents are attached to adjacent members of the base structure. For example, two ring-forming substituents attached to adjacent members of a cyclic base structure create a fused ring structure. In another embodiment, the ring-forming substituents are attached to a single member of the base structure. For example, two ring-forming substituents attached to a single member of a cyclic base structure create a spirocyclic structure. In yet another embodiment, the ring-forming substituents are attached to non-adjacent members of the base structure.

[0043] The compounds provided herein may exist in one or more specific geometric, optical, enantiomer, diastereomer, epimer, stereoisomer, tautomer, conformational, or anomeric forms, including, but not limited to, cis- and trans- forms; E- and Z- forms; endo- and exo- forms; R-, S-, and meso- forms; D- and L- forms; d- and l- forms; (+) and (-) forms; keto-, enol-, and enolate- forms; syn- and anti- forms; synclinal and anticlinal forms; α- and β- forms; axial and equatorial forms; boat-, chair-, twist-, envelope-, and semi-chair- forms; and combinations thereof.

[0044] The compounds described herein may contain one or more chiral centers and thus may exist in various isomeric forms, such as enantiomers and / or diastereomers. For example, the compounds described herein may be in the form of individual enantiomers, diastereomers or geometric isomers, or in the form of a mixture of stereoisomers, including racemic mixtures and mixtures in which one or more stereoisomers are concentrated. In one embodiment, the stereochemical configuration exhibited in the compound is relative rather than absolute. Isomers can be isolated from the mixture by methods known to those skilled in the art, including chiral high-pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric 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 (ELEliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972). This disclosure further encompasses the compounds described herein as individual isomers substantially free of other isomers, and instead as mixtures of various isomers.

[0045] As used herein, a pure enantiomeric compound is substantially free of other enantiomers or stereoisomers of the compound (i.e., enantiomeric-rich). In other words, the “S” form of the compound is substantially free of the “R” form of the compound, and the “R” form is enantiomeric-rich. The terms “enantiomerically pure” or “pure enantiomer” indicate that the compound contains more than 75% by weight, more than 80% by weight, more than 85% by weight, more than 90% by weight, more than 91% by weight, more than 92% by weight, more than 93% by weight, more than 94% by weight, more than 95% by weight, more than 96% by weight, more than 97% by weight, more than 98% by weight, more than 99% by weight, more than 99.5% by weight, or more than 99.9% by weight of enantiomers. In certain embodiments, weight is based on the total weight of all enantiomers or stereoisomers of the compound.

[0046] In the compositions provided herein, enantiomers pure compounds may be present together with other active or inactive components. For example, a pharmaceutical composition containing an enantiomers pure R-compound may contain, for example, about 90% additives and about 10% enantiomers pure R-compound. In certain embodiments, the enantiomers pure R-compound in such a composition may contain, for example, at least about 95% by weight of the R-compound and at most about 5% by weight of the S-compound, by the total weight of the compound. For example, a pharmaceutical composition containing an enantiomers pure S-compound may contain, for example, about 90% additives and about 10% enantiomers pure S-compound. In certain embodiments, the enantiomers pure S-compound in such a composition may contain, for example, at least about 95% by weight of the S-compound and at most about 5% by weight of the R-compound, by the total weight of the compound.

[0047] In some embodiments, diastereomerically pure compounds can be present together with other active or inactive components. For example, a pharmaceutical composition containing a diastereomerically pure exo compound may contain, for example, about 90% additives 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 at most about 5% by weight of the endo compound, by the total weight of the compound. For example, a pharmaceutical composition containing a diastereomerically pure endo compound may contain, for example, about 90% additives and about 10% 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 at most about 5% by weight of the exo compound, by the total weight of the compound.

[0048] In some embodiments, isomerically pure compounds can be present together with other active or inactive components. For example, a pharmaceutical composition containing an isomerically pure exo compound may contain, for example, about 90% additives and about 10% isomerically pure exo compounds. 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 at most about 5% by weight of the endo compound, by the total weight of the compound. For example, a pharmaceutical composition containing an isomerically pure endo compound may contain, for example, about 90% additives and about 10% isomerically pure endo compounds. 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 at most about 5% by weight of the exo compound, by the total weight of the compound.

[0049] In certain embodiments, the active ingredient can be formulated with or without small amounts of additives or carriers.

[0050] The compounds described herein may also include one or more isotopic substitutions. For example, H is 1 H, 2 H (D or deuterium), and 3 It can be any isotopic form including H (T or tritium); C is 12 C, 13 C, and 14 It can be any isotopic form including C; O is, 16 O and 18 It can be any isotopic form including O; N is, 14 N and 15 It can be any isotopic form including N; F is, 18 F, 19 This includes the possibility of any isotopic form, including F.

[0051] The term “pharmaceutically acceptable salt” means a salt of an active compound prepared with a relatively non-toxic acid or base by certain substituents found on the compounds described herein. When a compound of the disclosure contains relatively acidic functionality, 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 undiluted 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 invention contains relatively basic functionality, an acid addition salt can be obtained by contacting the neutral form of such a compound with a sufficient amount of the desired acid, either undiluted or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids, such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, monocarbonate, phosphoric acid, monohydrogen-phosphoric acid, dihydrogen-phosphoric acid, sulfuric acid, monohydrogen-sulfuric 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 alginic acid, and salts of organic acids, such as glucuronic acid or glucuronic acid (see, for example, Berge et al, Journal of Pharmaceutical Science 66:1-19 (1977)). Certain compounds of the present invention contain both basic and acidic functional groups that enable the compound to be converted into a base addition salt or an acid addition salt. 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.

[0052] In addition to salt forms, this disclosure provides compounds in prodrug forms. The prodrugs of the compounds described herein are those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the present invention. 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 having a suitable enzyme or chemical reagent.

[0053] The term "solvate" usually refers to a form of compound that has associated with a solvent through solvolysis. This physical association may include hydrogen bonding. Common solvents include water, methanol, ethanol, acetic acid, DMSO, THF, and diethyl ether. Compounds of formulas (I), (III), or (V) may be prepared, for example, in crystalline form and solvated. Suitable solvates include pharmaceutically acceptable solvates, and further include both stoichiometric and non-stoichiometric solvates. In certain cases, solvates can be isolated, for example, when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid. "Solvates" encompass both liquid-phase solvates and isolateable solvates. Representative solvates include hydrates, ethanolates, and methanelates.

[0054] The term "hydrate" refers to a compound that is associated with water. Typically, the number of water molecules contained in a compound hydrate is a fixed ratio to the number of compound molecules in the hydrate. Thus, a compound hydrate may 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 several types of hydrates, including, for example, monohydrates (x is 1), lower hydrates (x is a number greater than 0 and less than 1, e.g., hemihydrate (R·0.5H₂O)), and polyhydrates (x is a number greater than 1, e.g., dihydrate (R·2H₂O) and hexahydrate (R·6H₂O)).

[0055] The term "tautomer" refers to a compound that is an interchangeable form of a particular compound structure and differs in the transfer of hydrogen atoms and electrons. Thus, the two structures can be in equilibrium through the transfer of π electrons and atoms (usually H). For example, enols and ketones are tautomers because they are rapidly interconverted by treatment with acids or bases. Another example of tautomerism is the aci- and nitro-forms of phenylnitromethane, which are similarly formed by treatment with acids or bases. Tautomeristic forms can be relevant to achieving the optimal chemical reactivity and biological activity of the compound of interest.

[0056] Other definitions The following definitions are more general terms used throughout this disclosure.

[0057] The articles "a" and "an" refer to one or more (e.g., at least one) grammatical objects of the article. For example, "element" means one or more elements. The term "and / or" means "and" or "or" unless otherwise indicated.

[0058] The term “approximately” is used herein to mean a typical range acceptable in the art. For example, “approximately” can be understood as approximately two standard deviations from the mean. In certain embodiments, “approximately” means ±10%. In certain embodiments, “approximately” means ±5%. When “approximately” is presented before a series of numbers or ranges, it is understood that “approximately” can modify each of the numbers in the series of numbers or ranges.

[0059] "To obtain" or "to acquire," as used herein, means to possess a value, such as a numerical value, or an image, or a physical entity (such as a sample), by "directly obtaining" or "indirectly obtaining" the value or physical entity. "Directly obtaining" means performing a process (such as performing an analytical method or protocol) to obtain the value or physical entity. "Indirectly obtaining" means receiving the value or physical entity from another party or source (such as 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 in the physical entity or the use of a machine or apparatus. An example of directly obtaining a value is obtaining a sample from a human subject. Directly obtaining a value includes performing a process that involves using a machine or apparatus, such as a mass spectrometer to obtain mass spectrometry data.

[0060] The terms “administer,” “dosing,” or “administer” mean, as used herein, embedding, absorbing, ingesting, injecting, inhaling, or introducing the compounds of the present invention or their pharmaceutical compositions into another body.

[0061] In this specification, the terms “condition,” “disease,” and “disorder” are to be used interchangeably.

[0062] The “effective amount” of a compound of formula (I), (III), or (V) refers to an amount sufficient to elicit a desired biological response, i.e., to treat a condition. As those skilled in the art will recognize, the effective amount of a compound of formula (I), (III), or (V) may 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. Effective amounts encompass both therapeutic and prophylactic treatments. For example, in the treatment of cancer, an effective amount of the compound of the present invention may reduce tumor burden or halt tumor growth or spread.

[0063] The “therapeutic effective dose” of a compound of formula (I), (III), or (V) is the amount sufficient to achieve a therapeutic benefit in the treatment of a condition or to delay or minimize one or more symptoms associated with that condition. In some embodiments, the therapeutic effective dose is the amount sufficient to achieve a therapeutic benefit in the treatment of a condition or to minimize one or more symptoms associated with that condition. The therapeutic effective dose of a compound means the amount of the therapeutic agent, alone or in combination with other treatments, that achieves a therapeutic benefit in the treatment of a condition. The term “therapeutic effective dose” may include an amount that improves the overall treatment, reduces or avoids the symptoms or causes of a condition, or enhances the therapeutic effect of another therapeutic agent.

[0064] The terms “peptide,” “polypeptide,” and “protein” are used interchangeably and refer to compounds consisting 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 linked to each other by peptide bonds. As used herein, this term refers to both short chains (commonly referred to in the art, for example, as peptides, oligopeptides, and oligomers) and longer chains (commonly referred to in the art as proteins, of which many types exist).

[0065] "Prevention," "preventing," and "preventing" as used herein refer to a treatment, for example, administering a compound described herein (e.g., a compound of formula (I), (III), or (V)) before the onset of a disease, disorder, or condition, in order to prevent the physical manifestation of the disease, disorder, or condition. In some embodiments, "prevention," "preventing," and "preventing" require that no signs or symptoms of the disease, disorder, or condition have occurred or have not yet been observed. In some embodiments, the treatment includes prevention, while in other embodiments it does not.

[0066] The “subjects” to which the drug is intended to be administered include, but are not limited to, humans (i.e., males or females of any age group, e.g., pediatric subjects (e.g., infants, children, adolescents) or adult subjects (e.g., young adults, middle-aged adults, or elderly adults)) and / or other non-human animals, e.g., mammals (e.g., primates (e.g., crab-eating macaques, rhesus macaques); commercially relevant mammals, e.g., cattle, pigs, horses, sheep, goats, cats, and / or dogs) and birds (e.g., commercially relevant birds, e.g., 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.

[0067] As used herein, the terms “treatment,” “to treat,” and “to treat” mean, for example, administering a treatment, for example, administering a compound described herein (for example, a compound of formula (I), (III), or (V)) to reverse, alleviate, delay the onset, or inhibit the progression of one or more of the symptoms, manifestation, or underlying causes of a disease, disorder, or condition (for example, as described herein). In one embodiment, treating includes reducing, reversing, alleviating, delaying the onset, or inhibiting the progression of the symptoms of a disease, disorder, or condition. In one embodiment, treating includes reducing, reversing, alleviating, delaying the onset, or inhibiting the progression of the manifestation of a disease, disorder, or condition. In one embodiment, treating includes reducing, reversing, alleviating, reducing, or delaying the onset of the underlying causes of a disease, disorder, or condition. In some embodiments, “treatment,” “to treat,” and “to treat” require that signs or symptoms of a disease, disorder, or condition have occurred or been observed. In other embodiments, the treatment may be administered, for example, in a prophylactic treatment, in the absence of signs or symptoms of the disease or condition. For example, the treatment may be administered to a susceptible individual before the onset of symptoms (for example, based on symptom history and / or genetic or other susceptibility factors). The treatment may also be continued after the symptoms have subsided, for example, to delay or prevent relapse. In some embodiments, the treatment includes prophylactic treatment, while in other embodiments, it does not.

[0068] "Proliferative disorders" refer to diseases caused by abnormal elongation due to cell proliferation (Walker, Cambridge Dictionary of Biology; Cambridge University Press: Cambridge, UK, 1990). Proliferative disorders may be associated with: 1) pathological proliferation of normally quiescent cells; 2) pathological migration of cells from their normal locations (e.g., metastasis of neogenes); 3) pathological expression of proteolytic enzymes, e.g., matrix metalloproteinases (e.g., collagenase, gelatinase, and elastase); 4) pathological angiogenesis, such as in proliferative retinopathy and tumor metastasis; or 5) evasion of host immune surveillance and removal of neogenes. Exemplary proliferative disorders include cancer (i.e., "malignant neoplasms"), benign neoplasms, and angiogenesis.

[0069] "Nonproliferative disorders" refer to diseases that do not primarily involve the abnormal proliferation of cells. Nonproliferative disorders may be associated with any cell type or tissue type in the subject. Exemplary nonproliferative disorders include neurological disorders or disorders (e.g., repeat diseases); autoimmune disorders or disorders; immunodeficiency disorders or disorders; lysosomal storage disorders or disorders; inflammatory disorders or disorders; cardiovascular conditions, diseases or disorders; metabolic disorders or disorders; respiratory conditions, diseases or disorders; renal diseases or disorders; and infections.

[0070] compound In one embodiment, the present disclosure relates to a compound of formula (I). [ka] or characterized by a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, and each of these is one or more R 1 It is replaced by an optional choice; L 1 and L 2 Each of these is independently: non-existent, C1~C6-alkylene, C1~C6-heteroalkylene, -O-, -C(O)-, -N(R 8)-,-N(R 8 )C(O)-, or -C(O)N(R 8 )- where each alkylene and heteroalkylene is one or more R 9 They are replaced by choice; W, X, and Z are each independently replaced by C(R 3 ) or N; Y is N, N(R 4a ), C(R 4b ), or C(R 4b )(R 4c ) where the dashed lines in the ring containing Y may be single or double bonds as the valence allows; each R 1 These are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 5 It is either replaced by an arbitrary choice; 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 group, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl group has one or more R groups. 5 It is replaced by choice; R 2 R is absent, hydrogen, or C1-C6 alkyl; 3is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D ; R 4a is hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, or C1-C6-haloalkyl; R 4b and R 4c each are independently hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, or -OR A ; each R 5 is independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D , -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D ; wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R 6 ; each R 6 is independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A ; each R 8 is independently hydrogen, C1-C6-alkyl, or C1-C6-haloalkyl; each R 9These are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, halo, cyano, oxo, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and; each R A These are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, and -C(O)R D , or -S(O) x R D and; each R B and R C These are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, and -OR A is it; or R B and R C Along with the atoms to which they are attached, one or more R 10 They form a 3- to 7-membered heterocyclyl ring which is optionally substituted; each R D R is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl; each R 10 x is independently a C1-C6 alkyl or halo; x is 0, 1, or 2.

[0071] In another embodiment, the present disclosure relates to a compound of formula (III). [ka] or characterized by a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, and each of these is one or more R 1 It is replaced by an optional choice; L1 and L 2 Each of these is independently: non-existent, C1~C6-alkylene, C1~C6-heteroalkylene, -O-, -C(O)-, -N(R 8 )-,-N(R 8 )C(O)-, or -C(O)N(R 8 )- where each alkylene and heteroalkylene is one or more R 9 It is replaced by choice; X and Z are independently replaced by C(R 3 ) or N; Y is N, C, or C(R 4b ) where the dashed lines in the ring containing Y may be single or double bonds as the valence allows; each R 1 These are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 5 It is either replaced by an arbitrary choice; 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 group, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl group has one or more R groups. 5 It is replaced by choice; R 2R is absent, hydrogen, or C1-C6 alkyl; 3 These are hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D And; R 4b R is hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, or C1-C6 haloalkyl; each R 5 These are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 6 It is replaced by an optional choice; each R 6 These are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A And; R 7a This refers to hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, oxo, or -OR A And; R 7b This refers to hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR. A and; each R8 R is independently hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl; each R 9 These are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, halo, cyano, oxo, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and; each R A These are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, and -C(O)R D , or -S(O) x R D and; each R B and R C These are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, and -OR A is it; or R B and R C Along with the atoms to which they are attached, one or more R 10 They form a 3- to 7-membered heterocyclyl ring which is optionally substituted; each R D R is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl; each R 10 x is independently a C1-C6 alkyl or halo; x is 0, 1, or 2.

[0072] In another embodiment, the present disclosure relates to compounds of formula (V). [ka] or characterized by a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A is a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is one or more R 1 It is replaced by choice; R B is B, C1-C6-alkyl, or C1-C6-heteroalkyl, where alkyl and heteroalkyl are one or more R 10 It is substituted with; B is a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which has one or more R 1 These are optionally replaced; each of these is one or more R 1 It is replaced by an optional choice; L 1 and L 2 Each of these is independently: non-existent, 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 one or more R 9 It is replaced by an optional choice; Y is N, C(R 6a ), or C(R 6a )(R 6b ) where the dashed lines in the ring containing Y may be single or double bonds as the valence allows; each R 1 These are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D, -C(O)OR D , or -S(O) x R D Here, each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 5 It is either replaced by an arbitrary choice; 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 group, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl group has one or more R groups. 5 It is replaced by an optional choice; each R 2 R is independently hydrogen or a C1-C6 alkyl group; 3 C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D And; R 4 R is hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl; each R 5 These are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R DHere, each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 7 It is replaced by choice; R 6a and R 6b R is independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, or halo; each R 7 These 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 These are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, and -C(O)R D , or -S(O) x R D and; each R B and R C These are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, and -OR A is it; or R B and R C Along with the atoms to which they are attached, one or more R 9 They form a 3- to 7-membered heterocyclyl ring which is optionally substituted; each R D R is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl; each R 9 and R 10 x is independently a C1-C6 alkyl or halo; n is 0, 1, or 2; m is 0, 1, 2, or 3; and x is 0, 1, or 2.

[0073] In some embodiments, for formula (V), R BB is B, where B is a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which has one or more R 1 It is being replaced by an optional choice.

[0074] As is generally described herein for compounds of formulas (I), (III), and (V), each of A or B is independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which has one or more R 1 It is being replaced by an optional choice.

[0075] In some embodiments, A and B are independently monocyclic rings, such as monocyclic cycloalkyl, monocyclic heterocyclyl, monocyclic aryl, or monocyclic heteroaryl. The monocyclic rings may be saturated, partially unsaturated, or fully unsaturated (e.g., aromatic). In some embodiments, A or B are independently monocyclic rings 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 comprises one or more R 1 It is a monoring that has been optionally substituted.

[0076] In some embodiments, A or B is independently a bicyclic ring, e.g., a bicyclic cycloalkyl, bicyclic heterocyclyl, bicyclic aryl, or bicyclic heteroaryl. The bicyclic ring may be saturated, partially unsaturated, or fully unsaturated (e.g., aromatic). In some embodiments, A or B is independently a bicyclic ring comprising a fused ring system, a bridging ring system, or a spiro ring system. In some embodiments, A or B is independently a bicyclic ring containing 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 biring ring. In some embodiments, B is an 8-membered biring ring. In some embodiments, A is a 9-membered biring ring. In some embodiments, B is a 9-membered biring ring. In some embodiments, A is a 10-membered biring ring. In some embodiments, B is a 10-membered biring ring. In some embodiments, A is an 11-membered biring ring. In some embodiments, B is an 11-membered biring ring. In some embodiments, A is a 12-membered biring ring. In some embodiments, B is a 12-membered biring ring. In some embodiments, A or B independently comprises one or more R 1 It is a biring ring that has been substituted by arbitrary choice.

[0077] In some embodiments, A or B is independently a tricyclic ring, e.g., a tricyclic cycloalkyl, tricyclic heterocyclyl, tricyclic aryl, or 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 comprising a fused ring system, a bridging ring system, a 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 triring ring. In some embodiments, B is a 9-membered triring ring. In some embodiments, A is a 10-membered triring ring. In some embodiments, B is a 10-membered triring ring. In some embodiments, A or B independently comprises one or more R 1 It is a triring ring that has been arbitrarily substituted.

[0078] In some embodiments, A or B is independently a monocyclic cycloalkyl, a monocyclic heterocyclil, a monocyclic aryl, or a monocyclic heteroaryl. In some embodiments, A or B is independently a bicyclic cycloalkyl, a bicyclic heterocyclil, a bicyclic aryl, or a bicyclic heteroaryl. In some embodiments, A or B is independently a tricyclic cycloalkyl, a tricyclic heterocyclil, a tricyclic aryl, or a tricyclic heteroaryl. In some embodiments, A is a monocyclic heterocyclil. In some embodiments, B is a monocyclic heterocyclil. In some embodiments, A is a bicyclic heterocyclil. In some embodiments, B is a bicyclic heteroaryl. 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.

[0079] In some embodiments, A or B is independently a nitrogen-containing heterocycline, for example, a heterocycline containing one or more nitrogen atoms. The one or more nitrogen atoms of the nitrogen-containing heterocycline may be at any position in the ring. In some embodiments, the nitrogen-containing heterocycline is monocyclic, bicyclic, or tricyclic. In some embodiments, A or B is independently a heterocycline containing at least one, at least two, at least three, at least four, at least five, or at least six nitrogen atoms. In some embodiments, A is a heterocycline containing one nitrogen atom. In some embodiments, B is a heterocycline containing one nitrogen atom. In some embodiments, A is a heterocycline containing two nitrogen atoms. In some embodiments, B is a heterocycline containing two nitrogen atoms. In some embodiments, A is a heterocycline containing three nitrogen atoms. In some embodiments, B is a heterocycline containing three nitrogen atoms. In some embodiments, A is a heterocycline containing four nitrogen atoms. In some embodiments, B is a heterocycline containing four nitrogen atoms. In some embodiments, A or B is a nitrogen-containing heterocycline independently containing one or more further heteroatoms, such as oxygen, sulfur, boron, silicon, or phosphorus. In some embodiments, one or more nitrogen atoms in the nitrogen-containing heterocycline are, for example, R 1 It has been replaced with.

[0080] In some embodiments, A or B is independently a nitrogen-containing heteroaryl, for example, a heteroaryl containing one or more nitrogen atoms. The one or more nitrogen atoms of the nitrogen-containing heteroaryl may be 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 one, at least two, at least three, at least four, at least five, or at least six 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 comprising one or more further heteroatoms, such as oxygen, sulfur, boron, silicon, or phosphorus. In some embodiments, one or more nitrogen atoms in the nitrogen-containing heteroaryl are, for example, R 1 It has been replaced with.

[0081] In some embodiments, A is a six-membered nitrogen-containing heterocycline, for example, a six-membered heterocycline containing one or more nitrogen atoms. In some embodiments, A is a six-membered heterocycline containing one nitrogen atom. In some embodiments, A is a six-membered heterocycline containing two nitrogen atoms. In some embodiments, A is a six-membered heterocycline containing three nitrogen atoms. In some embodiments, A is a six-membered heterocycline containing four nitrogen atoms. The one or more nitrogen atoms of the six-membered nitrogen-containing heterocycline may be at any position in the ring. In some embodiments, A is one or more R 1It is a 6-membered nitrogen-containing heterocycline in which the nitrogen atoms are optionally substituted. In some embodiments, one or more nitrogen atoms of the 6-membered nitrogen-containing heterocycline are, for example, R 1 It is substituted with. In some embodiments, A is a six-membered nitrogen-containing heterocycline containing one or more further heteroatoms, such as oxygen, sulfur, boron, silicon, or phosphorus.

[0082] In some embodiments, B is a five-membered nitrogen-containing heterocycline or heteroaryl, for example, a five-membered heterocycline or heteroaryl containing one or more nitrogen atoms. In some embodiments, B is a five-membered heterocycline containing one nitrogen atom. In some embodiments, B is a five-membered heteroaryl containing one nitrogen atom. In some embodiments, B is a five-membered heterocycline containing two nitrogen atoms. In some embodiments, B is a five-membered heteroaryl containing two nitrogen atoms. In some embodiments, B is a five-membered heterocycline containing three nitrogen atoms. In some embodiments, B is a five-membered heteroaryl containing three nitrogen atoms. The one or more nitrogen atoms of the five-membered nitrogen-containing heterocycline or heteroaryl may be at any position in the ring. In some embodiments, B is one or more R 1 It is a 5-membered nitrogen-containing heterocycline that is optionally substituted with R. In some embodiments, B is one or more R 1 It is a 5-membered nitrogen-containing heteroaryl that is optionally substituted with R. In some embodiments, one or more nitrogen atoms of the 5-membered nitrogen-containing heterocyclyl or heteroaryl are, for example, R 1 It is substituted with. In some embodiments, B is a five-membered nitrogen-containing heterocyclyl or heteroaryl containing one or more further heteroatoms, such as oxygen, sulfur, boron, silicon, or phosphorus.

[0083] In some embodiments, B is one or more R 1It is a nitrogen-containing bicyclic heteroaryl (e.g., a 9-membered nitrogen-containing bicyclic heteroaryl) that is optionally substituted with R. 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. One or more nitrogen atoms in the 9-membered bicyclic heteroaryl may be at any position on the ring. In some embodiments, B is one or more R 1 It is a 9-membered bicyclic heteroaryl that is substituted with [the specified compound].

[0084] In some embodiments, A and B are, [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] Independently selected from, in the formula, each R 1These are as defined herein. In one embodiment, A and B are each independently a saturated, partially saturated, or unsaturated (e.g., aromatic) derivative of the above ring. In one embodiment, A and B are each independently a stereoisomer of the above ring.

[0085] In some embodiments, A and B are, [ka] [ka] Independently selected from, in the formula, each R 1 These are as defined herein. In one embodiment, A and B are each independently a saturated, partially saturated, or unsaturated (e.g., aromatic) derivative of the above ring. In one embodiment, A and B are each independently a stereoisomer of the above ring.

[0086] In some embodiments, A is a heterocyclyl. In some embodiments, A is a nitrogen-containing heterocyclyl. In some embodiments, A is a monocyclic nitrogen-containing heterocyclyl. In some embodiments, A is [ka] Selected from.

[0087] In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0088] In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0089] In some embodiments, A is [ka] Selected from.

[0090] In some embodiments, A is a heteroaryl compound. In some embodiments, A is a nitrogen-containing heteroaryl compound. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl compound. In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0091] In some embodiments, A is [ka] Selected from. In some embodiments, A is [ka] And in the formula, R 1 This is as defined herein. In some embodiments, A is [ka] Selected from.

[0092] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0093] In some embodiments, B is a heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] And in the formula, R 1 This is as defined herein.

[0094] In some embodiments, B is [ka] Selected from.

[0095] In some embodiments, B is a heterocyclyl. In some embodiments, B is a nitrogen-containing heterocyclyl. In some embodiments, B is a monocyclic nitrogen-containing heterocyclyl or a bicyclic nitrogen-containing heterocyclyl.

[0096] In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0097] In some embodiments, B is [ka] Selected from.

[0098] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] That is the case.

[0099] As generally described for formulas (I), (III), and (V), L 1 and L 2 Each of these may independently be non-existent, or C1~C6-alkylene, C1~C6-heteroalkylene, -O-, -C(O)-, -N(R 8 )-,-N(R 8 )C(O)-, or -C(O)N(R 8 )- may refer to a group, where each alkylene and heteroalkylene is one or more R 9 It is optionally replaced by L. In some embodiments, 1 is absent or C1-C6 heteroalkylene. In some embodiments, L 1 L is nonexistent. In some embodiments, L 1 is a C1-C6 heteroalkylene (e.g., -N(CH3)-). In some embodiments, L 2 is absent or C1-C6 heteroalkylene. In some embodiments, L 2 L is nonexistent. In some embodiments, L 2 This is a C1-C6 heteroalkylene (for example, -N(CH3)-).

[0100] As generally described for formula (I), W, X, and Z are independently N or C(R 3 ) may be. In some embodiments, W is C(R 3 )(for example, CH). In some embodiments, W is N. In some embodiments, X is C(R 3)(for example, CH). In some embodiments, X is N. In some embodiments, Z is C(R 3 )(for example, CH). In some embodiments, Z is N. In some embodiments, W and X are independently C(R 3 )(for example, CH). In some embodiments, each of W and Z is independently C(R 3 )(for example, CH). In some embodiments, each of X and Z is independently C(R 3 )(for example, CH). In some embodiments, each of W, X, and Z is independently C(R 3 )(For example, CH).

[0101] As generally stated for equation (I), Y is N, N(R 4a ), C(R 4b ), or C(R 4b )(R 4c ) is fine, where the dashed line in the ring containing Y may be a single bond or a double bond as the valence allows. In some embodiments, Y is N(R 4a ) or C(R 4b ) In some embodiments, Y is N(R 4a )(for example, NH). In some embodiments, Y is C(R 4b )(For example, CH).

[0102] In some embodiments, W is C(R 3 ) and Y is N(R 4a ) In some embodiments, W is CH and Y is NH. In some embodiments, X is C(R 3 ) and Y is N(R 4a ) In some embodiments, X is CH and Y is NH. In some embodiments, Z is C(R 3 ) and Y is N(R 4a ) In some embodiments, Z is CH and Y is NH. In some embodiments, W and X are independently C(R 3 ) and Y is N(R 4a) In some embodiments, W and X are independently C(R 3 ) and Y is NH. In some embodiments, W and Z are independently C(R 3 ) and Y is N(R 4a ) In some embodiments, W and Z are independently C(R 3 ) and Y is NH. In some embodiments, X and Z are independently C(R 3 ) and Y is N(R 4a ) In some embodiments, X and Z are independently C(R 3 ) and Y is NH. In some embodiments, each of W, X, and Z is independently C(R 3 ) and Y is N(R 4a In some embodiments, W, X, and Z are each independently CH, and Y is NH.

[0103] In some embodiments, W is C(R 3 ) and Y is N. In some embodiments, W is CH and Y is N. In some embodiments, X is C(R 3 ) and Y is N. In some embodiments, X is CH and Y is N. In some embodiments, Z is C(R 3 ) and Y is N. In some embodiments, Z is CH and Y is N. In some embodiments, W and X are independently C(R 3 ) and Y is N. In some embodiments, W and X are independently C(R 3 ) and Y is N. In some embodiments, W and Z are independently C(R 3 ) and Y is N. In some embodiments, W and Z are independently C(R 3 ) and Y is N. In some embodiments, X and Z are independently C(R 3 ) and Y is N. In some embodiments, X and Z are independently C(R 3 ) and Y is N. In some embodiments, each of W, X, and Z is independently C(R 3) and Y is N. In some embodiments, each of W, X, and Z is independently CH and Y is N.

[0104] In some embodiments, R 2 It is non-existent.

[0105] In some embodiments, R 1 is C1-C6 alkyl. In some embodiments, R 1 is CH3. In some embodiments, A is 0 or 1 R 1 It is replaced by . In some embodiments, B is replaced by 0, 1 or 2 R 1 It has been replaced with.

[0106] In some embodiments of formula (I), A is a bicyclic heteroaryl and B is a monocyclic heterocyclyl. In some embodiments of formula (I), Z is N. In some embodiments of formula (I), W, X, and Z are each independently C(R 3 ), for example, not (CH). In some embodiments of formula (I), the compound is not one of the compounds disclosed in International Publication No. 2020 / 004594.

[0107] In some embodiments, the compound of formula (I) is the compound of formula (Ia). [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 contains one or more R 1 It is replaced by an optional choice; L 1 These are non-existent, C1~C6-alkylene, C1~C6-heteroalkylene, -O-, -C(O)-, -N(R 8 )-,-N(R 8 )C(O)-, or -C(O)N(R 8)- where each alkylene and heteroalkylene is one or more R 9 They are replaced by choice; W, X, and Z are each independently replaced by C(R 3 ) or N; Y is N, N(R 4a ), C(R 4b ), or C(R 4b )(R 4c ) where the dashed lines in the ring containing Y may be single or double bonds as the valence allows; each R 1 These are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 5 It is either replaced by an arbitrary choice; 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 group, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl group has one or more R groups. 5 It is replaced by choice; R 2 R is absent, hydrogen, or C1-C6 alkyl; 3These are hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D And; R 4a R is hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, or C1-C6 haloalkyl; 4b and R 4c Each of these can independently be hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, or -OR A and; each R 5 These are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 6 It is replaced by an optional choice; each R 6 These are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and; each R 8 R is independently hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl; each R 9These are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, halo, cyano, oxo, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and; each R A These are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, and -C(O)R D , or -S(O) x R D and; each R B and R C These are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, and -OR A is it; or R B and R C Along with the atoms to which they are attached, one or more R 10 They form a 3- to 7-membered heterocyclyl ring which is optionally substituted; each R D R is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl; each R 10 x is independently a C1-C6 alkyl or halo; x is 0, 1, or 2.

[0108] In some embodiments, A is one or more R 1 It is a heterocycline that is optionally substituted. In some embodiments, A is a monocyclic nitrogen-containing heterocycline. In some embodiments, A is optionally substituted with piperidinil. In some embodiments, A is [ka] Selected from, in the formula, R 1This is as defined herein.

[0109] In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, A is [ka] Selected from. In some embodiments, A is [ka] Selected from.

[0110] In some embodiments, A is a heteroaryl compound. In some embodiments, A is a nitrogen-containing heteroaryl compound. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl compound.

[0111] In some embodiments, A is [ka] Selected from. In some embodiments, A is [ka] And in the formula, R 1 This is as defined herein. In some embodiments, A is [ka] Selected from.

[0112] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0113] In some embodiments, B is a heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] And in the formula, R 1 This is as defined herein.

[0114] In some embodiments, B is [ka] Selected from.

[0115] In some embodiments, B is a heterocyclyl. In some embodiments, B is a nitrogen-containing heterocyclyl. In some embodiments, B is a monocyclic nitrogen-containing heterocyclyl or a bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0116] In some embodiments, B is [ka] Selected from.

[0117] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] That is the case.

[0118] In some embodiments, L 1 is absent or N(CH3). In some embodiments, L 1 L is nonexistent. In some embodiments, L 1 It is N(CH3).

[0119] In some embodiments, W, X, and Z are independently N or C(R 3 ) may be. In some embodiments, W is C(R 3 )(for example, CH). In some embodiments, W is N. In some embodiments, X is C(R 3 )(for example, CH). In some embodiments, X is N. In some embodiments, Z is C(R 3 )(for example, CH). In some embodiments, Z is N. In some embodiments, W and X are independently C(R 3 )(for example, CH). In some embodiments, each of W and Z is independently C(R 3 )(for example, CH). In some embodiments, each of X and Z is independently C(R 3 )(for example, CH). In some embodiments, each of W, X, and Z is independently C(R 3 )(For example, CH).

[0120] In some embodiments, R 4a is hydrogen or a C1-C6 alkyl group. In some embodiments, R 4a It is hydrogen.

[0121] In some embodiments, R 1 is C1-C6 alkyl. In some embodiments, R 1 is CH3. In some embodiments, A is 0 or 1 R 1 It is replaced by . In some embodiments, B is replaced by 0, 1 or 2 R 1 It has been replaced with.

[0122] In some embodiments, A is a bicyclic heteroaryl and B is a monocyclic heterocyclyl. In some embodiments of formula (I), Z is N. In some embodiments of formula (I), W, X, and Z are independently C(R 3 ), for example, not (CH).

[0123] In some embodiments, the compound of formula (I) is the compound of formula (Ib). [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, where A and B are independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which contains one or more R 1 It is replaced by an optional choice; L 1 These are non-existent, C1~C6-alkylene, C1~C6-heteroalkylene, -O-, -C(O)-, -N(R 8 )-,-N(R 8 )C(O)-, or -C(O)N(R 8 )- where each alkylene and heteroalkylene is one or more R 9 They are replaced by choice; W, X, and Z are each independently replaced by C(R 3 ) or N; each R 1 These are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) xR D Here, each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 5 It is either replaced by an arbitrary choice; 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 group, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl group has one or more R groups. 5 It is replaced by choice; R 3 These are hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D And; R 4a R is hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, or C1-C6 haloalkyl; each R 5 These are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 6 It is replaced by an optional choice; each R 6These are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and; each R 8 R is independently hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl; each R 9 These are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, halo, cyano, oxo, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and; each R A These are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, and -C(O)R D , or -S(O) x R D and; each R B and R C These are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, and -OR A is it; or R B and R C Along with the atoms to which they are attached, one or more R 10 They form a 3- to 7-membered heterocyclyl ring which is optionally substituted; each R D R is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl; each R 10 x is independently a C1-C6 alkyl or halo; x is 0, 1, or 2.

[0124] In some embodiments, A is one or more R 1It is a heterocycline that is optionally substituted. In some embodiments, A is a monocyclic nitrogen-containing heterocycline. In some embodiments, A is optionally substituted with piperidinil. In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0125] In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0126] In some embodiments, A is [ka] Selected from.

[0127] In some embodiments, A is a heteroaryl compound. In some embodiments, A is a nitrogen-containing heteroaryl compound. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl compound.

[0128] In some embodiments, A is [ka] Selected from. In some embodiments, A is [ka] And in the formula, R 1 This is as defined herein. In some embodiments, A is [ka] Selected from.

[0129] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0130] In some embodiments, B is a heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] And in the formula, R 1 This is as defined herein.

[0131] In some embodiments, B is [ka] Selected from.

[0132] In some embodiments, B is a heterocyclyl. In some embodiments, B is a nitrogen-containing heterocyclyl. In some embodiments, B is a monocyclic nitrogen-containing heterocyclyl or a bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein.

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

[0134] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] That is the case.

[0135] In some embodiments, L 1 is absent or N(CH3). In some embodiments, L 1 L is nonexistent. In some embodiments, L 1 It is N(CH3).

[0136] In some embodiments, W, X, and Z are independently N or C(R 3 ) may be. In some embodiments, W is C(R 3 )(for example, CH). In some embodiments, W is N. In some embodiments, X is C(R 3 )(for example, CH). In some embodiments, X is N. In some embodiments, Z is C(R 3 )(for example, CH). In some embodiments, Z is N. In some embodiments, W and X are independently C(R 3 )(for example, CH). In some embodiments, each of W and Z is independently C(R 3 )(for example, CH). In some embodiments, each of X and Z is independently C(R 3 )(for example, CH). In some embodiments, each of W, X, and Z is independently C(R 3 )(For example, CH).

[0137] In some embodiments, R 4a is hydrogen or a C1-C6 alkyl group. In some embodiments, R 4a It is hydrogen.

[0138] In some embodiments, R 1 is C1-C6 alkyl. In some embodiments, R 1is CH3. In some embodiments, A is 0 or 1 R 1 It is replaced by . In some embodiments, B is replaced by 0, 1 or 2 R 1 It has been replaced with.

[0139] In some embodiments, A is a bicyclic heteroaryl and B is a monocyclic heterocyclyl. In some embodiments of formula (I), Z is N. In some embodiments of formula (I), W, X, and Z are independently C(R 3 ), for example, not (CH).

[0140] In some embodiments, the compound of formula (I) is the compound of formula (Ic). [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 contains one or more R 1 It is replaced by an optional choice; Y is N, N(R 4a ), C(R 4b ), or C(R 4b )(R 4c ) where the dashed lines in the ring containing Y may be single or double bonds as the valence allows; each R 1 These 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)ORD , or -S(O) x R D Here, each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 5 It is either replaced by an arbitrary choice; 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 group, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl group has one or more R groups. 5 It is replaced by choice; R 2 R is absent, hydrogen, or C1-C6 alkyl; 4a R is hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, or C1-C6 haloalkyl; 4b and R 4c Each of these can independently be hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, or -OR A and; each R 5 These are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 6 It is replaced by an optional choice; each R 6These 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 These are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, and -C(O)R D , or -S(O) x R D and; each R B and R C These are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, and -OR A is it; or R B and R C Along with the atoms to which they are attached, one or more R 10 They form a 3- to 7-membered heterocyclyl ring which is optionally substituted; each R D R is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl; each R 10 x is independently a C1-C6 alkyl or halo; x is 0, 1, or 2.

[0141] In some embodiments, A is one or more R 1 It is a heterocycline that is optionally substituted. In some embodiments, A is a monocyclic nitrogen-containing heterocycline. In some embodiments, A is optionally substituted with piperidinil. In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0142] In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0143] In some embodiments, A is [ka] Selected from.

[0144] In some embodiments, A is a heteroaryl compound. In some embodiments, A is a nitrogen-containing heteroaryl compound. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl compound.

[0145] In some embodiments, A is [ka] Selected from. In some embodiments, A is [ka] And in the formula, R 1 This is as defined herein. In some embodiments, A is [ka] Selected from.

[0146] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0147] In some embodiments, B is a heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] And in the formula, R 1 This is as defined herein.

[0148] In some embodiments, B is [ka] Selected from.

[0149] In some embodiments, B is a heterocyclyl. In some embodiments, B is a nitrogen-containing heterocyclyl. In some embodiments, B is a monocyclic nitrogen-containing heterocyclyl or a bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0150] In some embodiments, B is [ka] Selected from.

[0151] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] That is the case.

[0152] As is generally stated, Y is N, N(R 4a ), C(R 4b ), or C(R 4b )(R 4c) can be, where the dashed line in the ring containing Y may be a single bond or a double bond as the valence allows. In some embodiments, Y is N(R 4a ) or C(R 4b ) In some embodiments, Y is N(R 4a )(for example, NH). In some embodiments, Y is C(R 4b )(For example, CH).

[0153] In some embodiments, R 2 It is non-existent.

[0154] In some embodiments, R 1 is C1-C6 alkyl. In some embodiments, R 1 is CH3. In some embodiments, A is 0 or 1 R 1 It is replaced by . In some embodiments, B is replaced by 0, 1 or 2 R 1 It has been replaced with.

[0155] In some embodiments, A is a bicyclic heteroaryl and B is a monocyclic heterocyclyl. In some embodiments of formula (I), Z is N. In some embodiments of formula (I), W, X, and Z are independently C(R 3 ), for example, not (CH).

[0156] In some embodiments, the compound of formula (I) is the compound of formula (Id). [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A is one or more R 1 A monocyclic nitrogen-containing heterocycline in which R is optionally substituted; B is one or more R 1 It is a bicyclic nitrogen-containing heteroaryl that is optionally substituted with; each R 1These are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 5 It is either replaced by an arbitrary choice; 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 group, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl group has one or more R groups. 5 It is replaced by an optional choice; each R 5 These are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R DHere, each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 6 It is replaced by an optional choice; each R 6 These 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 These are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, and -C(O)R D , or -S(O) x R D and; each R B and R C These are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, and -OR A is it; or R B and R C Along with the atoms to which they are attached, one or more R 10 They form a 3- to 7-membered heterocyclyl ring which is optionally substituted; each R D R is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl; each R 10 x is independently a C1-C6 alkyl or halo; x is 0, 1, or 2.

[0157] In some embodiments, A is one or more R 1 It is a heterocycline that is optionally substituted. In some embodiments, A is a monocyclic nitrogen-containing heterocycline. In some embodiments, A is optionally substituted with piperidinil. In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0158] In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0159] In some embodiments, A is [ka] Selected from.

[0160] In some embodiments, A is a heteroaryl compound. In some embodiments, A is a nitrogen-containing heteroaryl compound. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl compound.

[0161] In some embodiments, A is [ka] Selected from. In some embodiments, A is [ka] And in the formula, R 1 This is as defined herein. In some embodiments, A is [ka] Selected from.

[0162] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0163] In some embodiments, B is a heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] And in the formula, R 1 This is as defined herein.

[0164] In some embodiments, B is [ka] Selected from.

[0165] In some embodiments, B is a heterocyclyl. In some embodiments, B is a nitrogen-containing heterocyclyl. In some embodiments, B is a monocyclic nitrogen-containing heterocyclyl or a bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein.

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

[0167] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] That is the case.

[0168] In some embodiments, R 1 is C1-C6 alkyl. In some embodiments, R 1 is CH3. In some embodiments, A is 0 or 1 R 1 It is replaced by . In some embodiments, B is replaced by 0, 1 or 2 R 1 It has been replaced with.

[0169] In some embodiments, the compound of formula (I) is selected from the compounds in Table 1, or from pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers thereof.

[0170] [Table 1]

[0171] [Table 2]

[0172] [Table 3]

[0173] [Table 4]

[0174] [Table 5]

[0175] [Table 6]

[0176] [Table 7]

[0177] [Table 8]

[0178] [Table 9]

[0179] [Table 10]

[0180] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 100, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0181] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 101, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0182] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 102, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0183] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 103, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0184] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperidinyl); B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 104, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0185] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperidinyl); B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 105, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0186] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperidinyl); B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 106, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0187] In some embodiments, in 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); L 1 and L 2Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 107, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0188] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperazinyl); B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 108, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0189] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperazinyl); B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 109, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0190] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperazinyl); B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 110, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0191] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperazinyl); B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 111, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0192] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl); B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 112, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0193] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl); B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 113, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0194] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperazinyl); B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 114, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0195] In some embodiments, in 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); L 1 and L 2Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 115, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0196] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl); B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 116, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0197] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl); B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 117, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0198] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl); B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 118, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0199] In some embodiments, in 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); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 119, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0200] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperidinyl); B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl); L 1 is -N(R 8 )-(For example, -N(CH3)-) and L 2 is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a)(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 120, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0201] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperidinyl); B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl); L 1 is -N(R 8 )-(For example, -N(CH3)-) and L 2 is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 121, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0202] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperidinyl); B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl); L 1 is -N(R 8 )-(For example, -N(CH3)-) and L 2 is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 122, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0203] In some embodiments, in 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); L 1 is -N(R 8 )-(For example, -N(CH3)-) and L 2 is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 123, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0204] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 X and W are nonexistent; X and W are independently C(R) 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 124, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0205] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 125, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0206] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 126, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0207] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 127, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0208] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperidinyl); B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2X and W are nonexistent; X and W are independently C(R) 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 128, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0209] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperidinyl); B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 129, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0210] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperidinyl); B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 130, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0211] In some embodiments, in 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); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 131, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0212] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl); B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 X and W are nonexistent; X and W are independently C(R) 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 132, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0213] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl); B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 133, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0214] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl); B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 134, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0215] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl); B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 135, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0216] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperadyl); B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 136, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0217] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperadyl); B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 137, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0218] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperadyl); B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 138, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0219] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperadyl); B is a bicyclic heteroaryl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 139, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0220] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl); B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 140, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0221] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl); B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 141, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0222] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl); B is a bicyclic heteroaryl (e.g., 7-fluoro-2-methyl-2H-indazolyl); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 142, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0223] In some embodiments, in 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); L 1 and L 2 Each is nonexistent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 143, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0224] In some embodiments, in formula (I), A is a monocyclic heterocyclyl (e.g., piperidinyl); B is a bicyclic heteroaryl (e.g., 2-methyl-2H-indazolyl); L 1 is -N(R8 ) - (for example, -N(CH3)-); L 2 is non - existent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH); R 2 is non - existent. In some embodiments, the compounds of formula (I), (I - a) and (I - b) are compound 144, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer or stereoisomer thereof.

[0225] In some embodiments, for formula (I), A is monocyclic heterocyclyl (for example, piperidinyl); B is bicyclic heteroaryl (for example, 2,7 - dimethyl - 2H - indazolyl); L 1 is - N(R 8 )-(for example, -N(CH3)-); L 2 is non - existent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH); R 2 is non - existent. In some embodiments, the compounds of formula (I), (I - a) and (I - b) are compound 145, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer or stereoisomer thereof.

[0226] In some embodiments, for formula (I), A is monocyclic heterocyclyl (for example, piperidinyl); B is bicyclic heteroaryl (for example, 7 - fluoro - 2 - methyl - 2H - indazolyl); L 1 is - N(R 8 )-(for example, -N(CH3)-); L 2 is non - existent; X and W are each independently C(R 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH); R 2It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 146, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0227] In some embodiments, in 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); L 1 is -N(R 8 )-(For example, -N(CH3)-) and L 2 is nonexistent; X and W are independently C(R) 3 )(for example, CH); Z is N; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), and (Ib) are compound 147, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0228] In some embodiments, in formula (I), A is a bicyclic heterocyclyl (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heteroaryl (e.g., N-methylpiperazyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 165, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0229] In some embodiments, in formula (I), A is a bicyclic heterocyclyl (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heteroaryl (e.g., piperazyl); L 1and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 166, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0230] In some embodiments, in formula (I), A is a bicyclic heterocyclyl (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heteroaryl (e.g., N-methylpiperidinyl); L 1 L is non-existent; 2 is -N(R 8 )-(for example, -N(H)-); X, W, and Z are each independently C(R 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 167, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0231] In some embodiments, in formula (I), A is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); B is a monocyclic heteroaryl (e.g., piperidinyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 189, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0232] In some embodiments, in formula (I), A is a bicyclic heterocyclyl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heteroaryl (e.g., 4,7-diazaspiro[2.5]octanyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 190, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0233] In some embodiments, with respect to formula (I), A is a bicyclic heterocyclyl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heteroaryl (e.g., 4,7-diazaspiro[2.5]octanyl); L 1 and L 2 Each of them is nonexistent; X, W, and Z are each independently C(R) 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 191, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0234] In some embodiments, in formula (I), A is a bicyclic heterocyclyl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heteroaryl (e.g., piperidinyl); L 1 L is non-existent; 2 is -N(R 8 )-(for example, -N(H)-); X, W, and Z are each independently C(R 3 )(for example, CH) and; Y is N(R4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 192, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0235] In some embodiments, in formula (I), A is a bicyclic heterocyclyl (e.g., 5-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heteroaryl (e.g., piperidinyl); L 1 L is non-existent; 2 is -N(R 8 )-(for example, -N(H)-); X, W, and Z are each independently C(R 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 193, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0236] In some embodiments, in formula (I), A is a bicyclic heterocyclyl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heteroaryl (e.g., piperidinyl); L 1 L is non-existent; 2 is -N(R 8 )-(for example, -N(H)-); X, W, and Z are each independently C(R 3 )(for example, CH) and; Y is N(R 4a )(for example, NH) and; R 2 It is not present. In some embodiments, the compounds of formulas (I), (Ia), (Ib), and (Ic) are compound 238, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0237] In some embodiments, for formula (I), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); B is a bicyclic heteroaryl (e.g., 2,7-dimethyl-2H-indazolyl); L 1 is -N(R 8 )- (e.g., -N(CH3)-); L 2 is absent; X, W, and Z are each independently C(R 3 ) (e.g., CH); Y is N(R 4a ) (e.g., NH); R 2 is absent. In some embodiments, the compounds of formula (I), (I-a), (I-b) and (I-c) are compound 239, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0238] As generally described for formula (III), Y can be N, C, or C(R 4b ), where the dashed line in the ring containing Y can be a single bond or a double bond as valency permits. In some embodiments, Y is N or C. In some embodiments, Y is N (e.g., N). In some embodiments, Y is C.

[0239] In some embodiments, Z is C(R 3 ), and Y is N. In some embodiments, Z is CH, and Y is N. In some embodiments, X is C(R 3 ), and Y is N. In some embodiments, X is CH, and Y is N. In some embodiments, Z is C(R 3 ), and Y is N. In some embodiments, Z is CH, and Y is N. In some embodiments, Z and X are each independently C(R 3 ), and Y is N. In some embodiments, Z and X are each independently CH, and Y is N. In some embodiments, X and Z are each independently C(R 3 ), and Y is N. In some embodiments, X and Z are each independently C(R 3) and Y is N. In some embodiments, X and Z are independently CH and Y is N.

[0240] In some embodiments, the compound of formula (III) is the compound of formula (III-a). [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 contains one or more R 1 It is replaced by an optional choice; L 1 These are non-existent, C1~C6-alkylene, C1~C6-heteroalkylene, -O-, -C(O)-, -N(R 8 )-,-N(R 8 )C(O)-, or -C(O)N(R 8 )- where each alkylene and heteroalkylene is one or more R 9 It is replaced by choice; X and Z are independently replaced by C(R 3 ) or N; Y is N, C, or C(R 4b ) where the dashed lines in the ring containing Y may be single or double bonds as the valence allows; each R 1 These are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x RD Here, each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 5 It is either replaced by an arbitrary choice; 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 one or more R groups. 5 It is replaced by an optional choice; R 2 R is absent, hydrogen, or C1-C6 alkyl; 3 These are hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D And; R 4b R is hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, or C1-C6 haloalkyl; each R 5 These are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 6It is replaced by an optional choice; each R 6 These are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A And; R 7a This refers to hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, oxo, or -OR A And; R 7b This refers to hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR. A and; each R 8 R is independently hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl; each R 9 These are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, halo, cyano, oxo, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and; each R A These are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, and -C(O)R D , or -S(O) x R D and; each R B and R C These are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, and -OR A is it; or R B and R C Along with the atoms to which they are attached, one or more R 10 They form a 3- to 7-membered heterocyclyl ring which is optionally substituted; each R DR is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl; each R 10 x is independently a C1-C6 alkyl or halo; x is 0, 1, or 2.

[0241] In some embodiments, A is one or more R 1 It is a heterocycline that is optionally substituted. In some embodiments, A is a monocyclic nitrogen-containing heterocycline. In some embodiments, A is optionally substituted with piperidinil. In some embodiments, A is [ka] And in the formula, each R 1 A is independently hydrogen or C1-C6 alkyl. In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0242] In some embodiments, A is one or more R 1 It is a heteroaryl compound that is optionally substituted with A. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl compound. In some embodiments, A is optionally substituted with indazolyl. In some embodiments, A is optionally substituted with imidazo[1,2-a]pyridinyl. In some embodiments, A is [ka] And in the formula, each R 1 This is as defined herein. In some embodiments, A is [ka] In some embodiments, A is [ka] And in the formula, each R 1 This is as defined herein. In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0243] In some embodiments, B is one or more R 1 It is a heteroaryl that is optionally substituted. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is optionally substituted with indazolyl. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] That is the case.

[0244] In some embodiments, B is one or more R 1 It is a heterocyclyl that is optionally substituted. In some embodiments, B is a monocyclic nitrogen-containing heterocyclyl. In some embodiments, B is an optionally substituted piperazinyl. In some embodiments, B is [ka] And in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] In some embodiments, B is [ka] That is the case.

[0245] As is generally stated, Y is N, C, or C(R 4b ) can be, where the dashed line in the ring containing Y may be a single bond or a double bond as the valence allows. In some embodiments, Y is N. In some embodiments, Y is C. In some embodiments, Y is C(R 4b )(For example, CH).

[0246] In some embodiments, L 1 is absent or N(CH3). In some embodiments, L 1 L is nonexistent. In some embodiments, L 1 It is N(CH3).

[0247] In some embodiments, R 7a and R 7b Each of them is, independently, hydrogen.

[0248] In some embodiments, R2 It does not exist. In some embodiments, R 7 It is hydrogen.

[0249] In some embodiments, R 1 is C1-C6 alkyl. In some embodiments, R 1 is CH3. In some embodiments, A is 0 or 1 R 1 It is replaced by . In some embodiments, B is replaced by 0, 1 or 2 R 1 It has been replaced with.

[0250] In some embodiments, the compound of formula (III) is the compound of formula (III-b). [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 contains one or more R 1 It is replaced by an optional choice; L 1 These are non-existent, C1~C6-alkylene, C1~C6-heteroalkylene, -O-, -C(O)-, -N(R 8 )-,-N(R 8 )C(O)-, or -C(O)N(R 8 )- where each alkylene and heteroalkylene is one or more R 9 It is replaced by choice; X and Z are independently replaced by C(R 3 ) or N; each R 1 These 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 , -NRB 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 Here, each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 5 It is either replaced by an arbitrary choice; 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 one or more R groups. 5 It is replaced by an optional choice; R 3 These are hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and; each R 5 These are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R DHere, each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 6 It is replaced by an optional choice; each R 6 These are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A And; R 7a This refers to hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, oxo, or -OR A And; R 7b This refers to hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR. A and; each R 8 R is independently hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl; each R 9 These are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, halo, cyano, oxo, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D and; each R A These are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, and -C(O)R D , or -S(O) x R D and; each R B and R C These are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, and -OR A is it; or R B and R C Along with the atoms to which they are attached, one or more R 10 It forms a 3- to 7-membered heterocyclyl ring which is optionally substituted; Each R D R is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl; each R 10 x is independently a C1-C6 alkyl or halo; x is 0, 1, or 2.

[0251] In some embodiments, A is one or more R 1 It is a heterocycline that is optionally substituted. In some embodiments, A is a monocyclic nitrogen-containing heterocycline. In some embodiments, A is optionally substituted with piperidinil. In some embodiments, A is [ka] And in the formula, each R 1 A is independently hydrogen or C1-C6 alkyl. In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0252] In some embodiments, A is one or more R 1 It is a heteroaryl compound that is optionally substituted with A. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl compound. In some embodiments, A is optionally substituted with indazolyl. In some embodiments, A is optionally substituted with imidazo[1,2-a]pyridinyl. In some embodiments, A is [ka] And in the formula, each R 1 This is as defined herein. In some embodiments, A is [ka] In some embodiments, A is [ka] And in the formula, each R 1 This is as defined herein. In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0253] In some embodiments, B is one or more R 1 It is a heteroaryl that is optionally substituted. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is optionally substituted with indazolyl. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] In some embodiments, B is [ka] That is the case.

[0254] In some embodiments, B is one or more R 1 It is a heterocyclyl that is optionally substituted. In some embodiments, B is a monocyclic nitrogen-containing heterocyclyl. In some embodiments, B is an optionally substituted piperazinyl. In some embodiments, B is [ka] And in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] In some embodiments, B is [ka] That is the case.

[0255] In some embodiments, L 1 It is non-existent.

[0256] In some embodiments, X and Z are independently N or C(R 3 ) may be. In some embodiments, X is C(R 3 )(for example, CH). In some embodiments, X is N. In some embodiments, Z is C(R 3 )(for example, CH). In some embodiments, Z is N. In some embodiments, each of X and Z is independently C(R 3 )(for example, CH). In some embodiments, each of X and Z is independently C(R 3 )(For example, CH).

[0257] In some embodiments, R 1 is C1-C6 alkyl. In some embodiments, R 1 is CH3. In some embodiments, A is 0 or 1 R 1It is replaced by . In some embodiments, B is replaced by 0, 1 or 2 R 1 It has been replaced with.

[0258] In some embodiments, R 7a and R 7b Each of them is, independently, hydrogen.

[0259] In some embodiments, the compound of formula (III) is the compound of formula (III-c). [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 contains one or more R 1 It is optionally replaced with; Y is N, C, or C(R 4b ) where the dashed lines in the ring containing Y may be single or double bonds as the valence allows; each R 1 These are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 5It is either replaced by an arbitrary choice; 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 one or more R groups. 5 It is replaced by an optional choice; R 2 R is absent, hydrogen, or C1-C6 alkyl; 4a R is hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, or C1-C6 haloalkyl; each R 5 These are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 6 It is replaced by an optional choice; each R 6 These are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A And; R 7a This refers to hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, oxo, or -OR A And; R 7b This refers to hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or -OR. Aand; each R A These are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, and -C(O)R D , or -S(O) x R D and; each R B and R C These are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, and -OR A is it; or R B and R C Along with the atoms to which they are attached, one or more R 10 They form a 3- to 7-membered heterocyclyl ring which is optionally substituted; each R D R is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl; each R 10 x is independently a C1-C6 alkyl or halo; x is 0, 1, or 2.

[0260] In some embodiments, A is one or more R 1 It is a heterocycline that is optionally substituted. In some embodiments, A is a monocyclic nitrogen-containing heterocycline. In some embodiments, A is optionally substituted with piperidinil. In some embodiments, A is [ka] And in the formula, each R 1 A is independently hydrogen or C1-C6 alkyl. In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0261] In some embodiments, A is one or more R 1 It is a heteroaryl compound that is optionally substituted with A. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl compound. In some embodiments, A is optionally substituted with indazolyl. In some embodiments, A is optionally substituted with imidazo[1,2-a]pyridinyl. In some embodiments, A is [ka] And in the formula, each R 1 This is as defined herein. In some embodiments, A is [ka] In some embodiments, A is [ka] And in the formula, each R 1 This is as defined herein. In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0262] In some embodiments, B is one or more R 1It is a heteroaryl that is optionally substituted. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is optionally substituted with indazolyl. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] That is the case.

[0263] In some embodiments, Y is N, where the dashed lines in the ring containing Y may be single or double bonds as the valence allows. In some embodiments, Y is N or C(R 4b ) In some embodiments, Y is N (for example, N). In some embodiments, Y is C (R 4b )(For example, CH).

[0264] In some embodiments, L 1 It is non-existent.

[0265] In some embodiments, R 2 It is non-existent.

[0266] In some embodiments, R 7a and R 7b Each of them is, independently, hydrogen.

[0267] In some embodiments, R 1 is C1-C6 alkyl. In some embodiments, R 1 is CH3. In some embodiments, A is 0 or 1 R 1 It is replaced by . In some embodiments, B is replaced by 0, 1 or 2 R 1 It has been replaced with.

[0268] In some embodiments, the compound of formula (III) is selected from the compounds in Table 3, or from pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers thereof.

[0269] [Table 11]

[0270] [Table 12]

[0271] [Table 13]

[0272] [Table 14]

[0273] [Table 15]

[0274] [Table 16]

[0275] [Table 17]

[0276] [Table 18]

[0277] [Table 19]

[0278] [Table 20]

[0279] [Table 21]

[0280] [Table 22]

[0281] [Table 23]

[0282] [Table 24]

[0283] In some embodiments, in formula (III), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl); B is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7bEach of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 152, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0284] In some embodiments, in formula (III), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl); B is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 153, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0285] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 156, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0286] In some embodiments, with respect to formula (III), A is a bicyclic heterocyclyl (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 157, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0287] In some embodiments, with respect to formula (III), A is a monocyclic heterocyclyl (e.g., 1,2,3,6-tetrahydropyridinyl); B is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 158, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0288] In some embodiments, with respect to formula (III), A is a monocyclic heterocyclyl (e.g., N-methyl-1,2,3,6-tetrahydropyridinyl); B is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 159, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0289] In some embodiments, with respect to formula (III), A is a monocyclic heterocyclyl (e.g., 8-azabicyclo[3.2.1]octa-2-enyl); B is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 160, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0290] In some embodiments, with respect to formula (III), A is a monocyclic heterocyclyl (e.g., N-methyl-8-azabicyclo[3.2.1]octa-2-enyl); B is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 161, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0291] In some embodiments, in formula (III), A is a monocyclic heterocyclyl (e.g., piperidinyl); B is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); L 1 is -N(R 8 )-(for example, -NH-) and; L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 162, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0292] In some embodiments, with respect to formula (III), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); B is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); L 1 is -N(R 8 )-(for example, -NH-) and; L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 163, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0293] In some embodiments, in formula (III), A is a monocyclic heterocyclyl (e.g., piperidinyl); B is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 is nonexistent; X and Z are independently C(R)3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 172, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0294] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X is C(R 3 )(for example, CH); Z and Y are N, independently of each other; R 2 is non-existent; R 7a and R 7b These are, independently, hydrogen. In some embodiments, the compounds of formulas (III), (III-a), and (III-b) are compound 173, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0295] In some embodiments, in formula (III), A is a bicyclic heterocyclyl (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 174, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0296] In some embodiments, in formula (III), A is a bicyclic heterocyclyl (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heterocyclyl (e.g., N-methylpiperazyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 175, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0297] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 176, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0298] In some embodiments, with respect to formula (III), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); B is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 177, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0299] In some embodiments, in formula (III), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl); B is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 178, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0300] In some embodiments, with respect to formula (III), A is a bicyclic heterocyclyl (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heterocyclyl (e.g., 2,2,6,6-tetramethylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 179, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0301] In some embodiments, in formula (III), A is a monocyclic heterocyclyl (e.g., piperidinyl); B is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); L 1 is -N(R 8 )-(For example, -N(CH3)-) and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 180, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0302] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 181, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0303] In some embodiments, in formula (III), A is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 182, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0304] In some embodiments, with respect to formula (III), A is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); B is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); L 1 is -N(R 8 )-(for example, -NH-) and; L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 203, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0305] In some embodiments, in formula (III), A is a monocyclic heterocyclyl (e.g., piperidinyl); B is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); L 1 is -N(R 8 )-(for example, -NH-) and; L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 204, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0306] In some embodiments, with respect to formula (III), A is a bicyclic heterocycline (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 205, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0307] In some embodiments, with respect to formula (III), A is a bicyclic heterocycline (e.g., 7-fluoro-2-methyl-2H-indazolyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 206, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0308] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3)(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 207, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0309] In some embodiments, in formula (III), A is a bicyclic heterocyclyl (e.g., 2-methyl-2H-indazolyl); B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 208, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0310] In some embodiments, with respect to formula (III), A is a bicyclic heterocyclyl (e.g., 7-fluoro-2-methyl-2H-indazolyl); B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 209, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0311] In some embodiments, with respect to formula (III), A is a bicyclic heterocycline (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; X is C(R 3 )(for example, CH); Z is C(R 3 )(for example, CF); Y is N; R 2 is non-existent; R 7a and R 7b These are each independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), and (III-b) are compound 210, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0312] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X is C(R 3 )(for example, CH); Z is C(R 3 )(for example, CF); Y is N; R 2 is non-existent; R 7a and R 7b These are, independently, hydrogen. In some embodiments, the compounds of formulas (III), (III-a), and (III-b) are compound 227, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0313] In some embodiments, in formula (III), A is a monocyclic heterocyclyl (e.g., piperadyl); B is a bicyclic heterocyclyl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3)(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 228, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0314] In some embodiments, in formula (III), A is a monocyclic heterocyclyl (e.g., N-methylpiperazyl); B is a bicyclic heterocyclyl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 229, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0315] In some embodiments, with respect to formula (III), A is a bicyclic heterocycline (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; X is C(R 3 )(for example, CF) and; Z is C(R 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b These are, independently, hydrogen. In some embodiments, the compounds of formulas (III), (III-a), and (III-b) are compound 230, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0316] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X is C(R 3 )(for example, CF) and; Z is C(R 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), and (III-b) are compound 231, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0317] In some embodiments, in formula (III), A is a bicyclic heterocyclyl (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; X is C(R 3 )(for example, CF) and; Z is C(R 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), and (III-b) are compound 232, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0318] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X is C(R3 )(for example, CF) and; Z is C(R 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b These are, independently, hydrogen. In some embodiments, the compounds of formulas (III), (III-a), and (III-b) are compound 233, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0319] In some embodiments, in formula (III), A is a bicyclic heterocyclyl (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; X is C(R 3 )(for example, Ch); Z is C(R 3 )(for example, CF); Y is N; R 2 is non-existent; R 7a and R 7b These are, independently, hydrogen. In some embodiments, the compounds of formulas (III), (III-a), and (III-b) are compound 234, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0320] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X is C(R 3 )(for example, Ch); Z is C(R 3 )(for example, CF); Y is N; R 2 is non-existent; R 7a and R 7bThese are, independently, hydrogen. In some embodiments, the compounds of formulas (III), (III-a), and (III-b) are compound 235, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0321] In some embodiments, with respect to formula (III), A is a bicyclic heterocyclyl (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 236, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0322] In some embodiments, with respect to formula (III), A is a bicyclic heterocycline (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., 2,2-dimethylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 237, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0323] In some embodiments, in formula (III), A is a monocyclic heterocyclyl (e.g., piperadyl); B is a bicyclic heterocyclyl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 241, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0324] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X is C(R 3 )(for example, CF) and; Z is C(R 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b These are, independently, hydrogen. In some embodiments, the compounds of formulas (III), (III-a), and (III-b) are compound 242, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0325] In some embodiments, in formula (III), A is a bicyclic heterocyclyl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; X is C(R 3 )(for example, CF) and; Z is C(R 3)(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b These are, independently, hydrogen. In some embodiments, the compounds of formulas (III), (III-a), and (III-b) are compound 243, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0326] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 2,7-dimethylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 244, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0327] In some embodiments, with respect to formula (III), A is a bicyclic heterocycline (e.g., 4-fluoro-2-methylbenzo[d]oxazolyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 245, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0328] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 2,7-dimethylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 246, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0329] In some embodiments, in formula (III), A is a monocyclic heterocyclyl (e.g., pyrazolyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 284, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0330] In some embodiments, with respect to formula (III), A is a bicyclic heterocyclyl (e.g., 4-fluoro-2-methylbenzo[d]thiazolyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 285, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0331] In some embodiments, in formula (III), A is a bicyclic heterocyclyl (e.g., 6,8-dimethylimidazo[1,2-a]pyradyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 286, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0332] In some embodiments, with respect to formula (III), A is a bicyclic heterocycline (e.g., 6,8-dimethyl-[1,2,4]triazolo[1,5-a]pyradinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 287, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0333] In some embodiments, with respect to formula (III), A is a bicyclic heterocycline (e.g., 6,8-dimethyl-[1,2,4]triazolo[1,5-a]pyradinyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 288, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0334] In some embodiments, in formula (III), A is a bicyclic heterocyclyl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; X is C(R 3 )(for example, CH); Z is C(R 3 )(for example, CF); Y is N; R 2 is non-existent; R 7a and R 7b These are each independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), and (III-b) are compound 289, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0335] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X is C(R 3 )(for example, CH); Z is C(R 3)(for example, CF); Y is N; R 2 is non-existent; R 7a and R 7b These are, independently, hydrogen. In some embodiments, the compounds of formulas (III), (III-a), and (III-b) are compound 290, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0336] In some embodiments, in formula (III), A is a bicyclic heterocyclyl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 291, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0337] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 292, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0338] In some embodiments, with respect to formula (III), A is a bicyclic heterocycline (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., 2-methylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formula (III), (III-a), (III-b), and (III-c) are compounds 293, 294, 295, 296, or 323, or their pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0339] In some embodiments, in formula (III), A is a bicyclic heterocyclyl (e.g., 2-methylimidazo[1,2-a]pyradyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 297, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0340] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 4,6-dimethylpyrazolo[1,5-a]pyradyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3)(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 298, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0341] In some embodiments, in formula (III), A is a monocyclic heterocycline (e.g., pyrazolyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 299, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0342] In some embodiments, with respect to formula (III), A is a bicyclic heterocycline (e.g., 4-fluoro-2-methylbenzo[d]oxazolyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 300, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0343] In some embodiments, with respect to formula (III), A is a bicyclic heterocyclyl (e.g., 4-fluoro-2-methylbenzo[d]thiazolyl); B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 301, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0344] In some embodiments, in formula (III), A is a bicyclic heterocyclyl (e.g., 6,8-dimethylimidazo[1,2-a]pyradyl); B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 302, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0345] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 4,6-dimethylpyrazolo[1,5-a]pyradyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 303, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0346] In some embodiments, in formula (III), A is a bicyclic heterocycline (e.g., 4,6-dimethylpyrazolo[1,5-a]pyradyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 307, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0347] In some embodiments, in formula (III), A is a bicyclic heterocyclyl (e.g., 2-methylimidazo[1,2-a]pyradyl); B is a monocyclic heterocyclyl (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; X and Z are independently C(R) 3 )(for example, CH); Y is N; R 2 is non-existent; R 7a and R 7b Each of these is independently hydrogen. In some embodiments, the compounds of formulas (III), (III-a), (III-b), and (III-c) are compound 308, or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0348] In some embodiments, in formula (III), A is an oxygen-free bicyclic heteroaryl. In some embodiments, A is one or more R 1 It is a bicyclic heteroaryl substituted with, where R 1 It is not a halo. In some embodiments, A is [ka] isn't it.

[0349] In some embodiments, B is one or more R 1 It is a nitrogen-containing heterocycline in which R is optionally substituted, where R 1 is not a cycloalkyl (e.g., cyclopropyl). In some embodiments, B is an unsubstituted piperidinyl (e.g., 0 R 1 ). In some embodiments, B is [ka] Instead, in the formula, R 1 is a C1-C6 alkyl (e.g., methyl) or cycloalkyl (e.g., cyclopropyl). In some embodiments, B is [ka] And in the formula, R 1 is hydrogen. In some embodiments, B is [ka] No. In some embodiments, B is [ka] isn't it.

[0350] In some embodiments, X is C(R 3 ) and here, R 3 is a halo. In some embodiments, X is CF.

[0351] In some embodiments, the compound of formula (III) is not a compound disclosed in International Publication No. 2020 / 004594. In some embodiments, the compound of formula (III) is [ka] Not a compound selected from or a pharmaceutically acceptable salt thereof.

[0352] In some embodiments, the present disclosure relates to compounds of formula (Va). [ka] or characterized by a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A and B are each independently a cycloalkyl, heterocyclyl, aryl, or heteroaryl, and each of these is one or more R 1 It is replaced by an optional choice; L 1 and L 2 Each of these is independently: non-existent, 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 one or more R 7 It is replaced by an optional choice; Y is N, C(R 6a ), or C(R 6a )(R 6b ) where the dashed lines in the ring containing Y may be single or double bonds as the valence allows; each R 1 These 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 RC , -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 Here, each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 5 It is either replaced by an arbitrary choice; 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 one or more R groups. 5 It is replaced by an optional choice; each R 2 R is independently hydrogen or C1-C6 alkyl; 3 C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D And; R 4 R is hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl; each R 5 These are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O)x R D Here, each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 7 It is replaced by an optional choice; R 6a and R 6b R is independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, or halo; each R 7 These 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 These are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, and -C(O)R D , or -S(O) x R D and; each R B and R C These are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, and -OR A is it; or R B and R C Along with the atoms to which they are attached, one or more R 9 They form a 3- to 7-membered heterocyclyl ring which is optionally substituted; each R D R is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl; each R 9 x is independently a C1-C6 alkyl or halo; n is 0, 1, or 2; m is 0, 1, 2, or 3; and x is 0, 1, or 2.

[0353] In some embodiments, A is one or more R1 It is a heterocycline that is optionally substituted. In some embodiments, A is a monocyclic nitrogen-containing heterocycline. In some embodiments, A is optionally substituted with piperidinil. In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0354] In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0355] In some embodiments, A is [ka] Selected from.

[0356] In some embodiments, A is a heteroaryl compound. In some embodiments, A is a nitrogen-containing heteroaryl compound. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl compound.

[0357] In some embodiments, A is [ka] Selected from. In some embodiments, A is [ka] And in the formula, R 1 This is as defined herein. In some embodiments, A is [ka] Selected from.

[0358] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0359] In some embodiments, B is a heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] And in the formula, R 1 This is as defined herein.

[0360] In some embodiments, B is [ka] Selected from.

[0361] In some embodiments, B is a heterocyclyl. In some embodiments, B is a nitrogen-containing heterocyclyl. In some embodiments, B is a monocyclic nitrogen-containing heterocyclyl or a bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0362] In some embodiments, B is [ka] Selected from.

[0363] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] That is the case.

[0364] In some embodiments, the compound of formula (V) is of formula (Vb) [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 contains one or more R 1 It is replaced by an optional choice; L 1 These are independently: non-existent, 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 one or more R 7 It is replaced by an optional choice; each R 1 These are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R DHere, each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 5 It is either replaced by an arbitrary choice; 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 one or more R groups. 5 It is replaced by an optional choice; each R 2 R is independently hydrogen or C1-C6 alkyl; 3 C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D And; R 4 R is hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl; each R 5 These are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 7 It is replaced by an optional choice; each R 7These 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 These are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, and -C(O)R D , or -S(O) x R D and; each R B and R C These are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, and -OR A is it; or R B and R C Along with the atoms to which they are attached, one or more R 9 They form a 3- to 7-membered heterocyclyl ring which is optionally substituted; each R D R is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl; each R 9 x is independently a C1-C6 alkyl or halo; n is 0, 1, or 2; m is 0, 1, 2, or 3; and x is 0, 1, or 2.

[0365] In some embodiments, A is one or more R 1 It is a heterocycline that is optionally substituted. In some embodiments, A is a monocyclic nitrogen-containing heterocycline. In some embodiments, A is optionally substituted with piperidinil. In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0366] In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0367] In some embodiments, A is [ka] and [ka] Selected from.

[0368] In some embodiments, A is a heteroaryl compound. In some embodiments, A is a nitrogen-containing heteroaryl compound. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl compound.

[0369] In some embodiments, A is [ka] Selected from. In some embodiments, A is [ka] And in the formula, R 1 This is as defined herein. In some embodiments, A is [ka] Selected from.

[0370] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0371] In some embodiments, B is a heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] And in the formula, R 1 This is as defined herein.

[0372] In some embodiments, B is [ka] Selected from.

[0373] In some embodiments, B is a heterocyclyl. In some embodiments, B is a nitrogen-containing heterocyclyl. In some embodiments, B is a monocyclic nitrogen-containing heterocyclyl or a bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0374] In some embodiments, B is [ka] Selected from.

[0375] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] That is the case.

[0376] In some embodiments, the compound of formula (V) is of formula (Vc) [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 contains one or more R 1 It is replaced by an optional choice; L 1 These are independently: non-existent, 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 one or more R 7 It is replaced by an optional choice; each R 1 These are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 5 It is either replaced by an arbitrary choice; 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 one or more R groups. 5 It is replaced by an optional choice; each R 2 R is independently hydrogen or C1-C6 alkyl; 3 C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D And; R 4 R is hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl; each R 5 These are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 7 It is replaced by an optional choice; each R 7 These are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and; each R AThese are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, and -C(O)R D , or -S(O) x R D and; each R B and R C These are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, and -OR A is it; or R B and R C Along with the atoms to which they are attached, one or more R 9 They form a 3- to 7-membered heterocyclyl ring which is optionally substituted; each R D R is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl; each R 9 x is independently a C1-C6 alkyl or halo; n is 0, 1, or 2; and x is 0, 1, or 2.

[0377] In some embodiments, A is one or more R 1 It is a heterocycline that is optionally substituted. In some embodiments, A is a monocyclic nitrogen-containing heterocycline. In some embodiments, A is optionally substituted with piperidinil. In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0378] In some embodiments, A is [ka] Selected from, in the formula, R 1This is as defined herein.

[0379] In some embodiments, A is [ka] and [ka] Selected from.

[0380] In some embodiments, A is a heteroaryl compound. In some embodiments, A is a nitrogen-containing heteroaryl compound. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl compound.

[0381] In some embodiments, A is [ka] Selected from. In some embodiments, A is [ka] And in the formula, R 1 This is as defined herein. In some embodiments, A is [ka] Selected from.

[0382] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0383] In some embodiments, B is a heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] And in the formula, R 1 This is as defined herein.

[0384] In some embodiments, B is [ka] Selected from.

[0385] In some embodiments, B is a heterocyclyl. In some embodiments, B is a nitrogen-containing heterocyclyl. In some embodiments, B is a monocyclic nitrogen-containing heterocyclyl or a bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0386] In some embodiments, B is [ka] Selected from.

[0387] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] That is the case.

[0388] In some embodiments, the compound of formula (V) is of formula (Vd) [ka] or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein A is a cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is one or more R 1 It is replaced by an optional choice; R B1 These are C1-C6 alkyl or C1-C6 heteroalkyl, and each of these is R 10 It is replaced by an optional choice; L 1 These are independently: non-existent, 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 one or more R 7 It is replaced by an optional choice; each R 1 These are independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 5 It is either replaced by an arbitrary choice; 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 one or more R groups. 5 It is replaced by an optional choice; each R 2 R is independently hydrogen or C1-C6 alkyl; 3 C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, -OR A , -NR B R C , -C(O)R D , or -C(O)OR D And; R 4 R is hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl; each R 5 These are independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR A , -NR B R C , -NR B C(O)R D -NO2, -C(O)NR B R C , -C(O)R D , -C(O)OR D , or -S(O) x R D Here, each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R 7 It is replaced by an optional choice; each R 7 These are independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR A and; each R AThese are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, and -C(O)R D , or -S(O) x R D and; each R B and R C These are independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, and -OR A is it; or R B and R C Along with the atoms to which they are attached, one or more R 9 They form a 3- to 7-membered heterocyclyl ring which is optionally substituted; each R D R is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl; each R 9 and R 10 x is independently a C1-C6 alkyl or halo; n is 0, 1, or 2; and x is 0, 1, or 2.

[0389] In some embodiments, A is one or more R 1 It is a heterocycline that is optionally substituted. In some embodiments, A is a monocyclic nitrogen-containing heterocycline. In some embodiments, A is optionally substituted with piperidinil. In some embodiments, A is [ka] Selected from, in the formula, R 1 This is as defined herein.

[0390] In some embodiments, A is [ka] Selected from, in the formula, R1 This is as defined herein.

[0391] In some embodiments, A is [ka] Selected from.

[0392] In some embodiments, A is a heteroaryl compound. In some embodiments, A is a nitrogen-containing heteroaryl compound. In some embodiments, A is a bicyclic nitrogen-containing heteroaryl compound.

[0393] In some embodiments, A is [ka] Selected from. In some embodiments, A is [ka] And in the formula, R 1 This is as defined herein. In some embodiments, A is [ka] Selected from.

[0394] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] In some embodiments, A is [ka] That is the case.

[0395] In some embodiments, B is a heteroaryl. In some embodiments, B is a nitrogen-containing heteroaryl. In some embodiments, B is a bicyclic nitrogen-containing heteroaryl. In some embodiments, B is [ka] Selected from. In some embodiments, B is [ka] And in the formula, R 1 This is as defined herein.

[0396] In some embodiments, B is [ka] Selected from.

[0397] In some embodiments, B is a heterocyclyl. In some embodiments, B is a nitrogen-containing heterocyclyl. In some embodiments, B is a monocyclic nitrogen-containing heterocyclyl or a bicyclic nitrogen-containing heterocyclyl. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein. In some embodiments, B is [ka] Selected from, in the formula, R 1 This is as defined herein.

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

[0399] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] In some embodiments, B is [ka] That is the case.

[0400] In some embodiments, the compound of formula (V) is selected from the compounds in Table 5, or from their pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers.

[0401] Table 25

[0402] Table 26

[0403] Table 27

[0404] Table 28

[0405] Table 29

[0406] Table 30

[0407] Table 31

[0408] Table 32

[0409] Table 33

[0410] Table 34

[0411] Table 35

[0412] [Table 36]

[0413] [Table 37]

[0414] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 185, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0415] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 186, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0416] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 R is hydrogen; 3 is a halo (e.g., F); m is 1; and n is 2. In some embodiments, the compound of formula (V) is compound 187, 188, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0417] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 4-fluoro-2-methylbenzo[d]oxazolyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 215, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0418] In some embodiments, with respect to formula (V), A is a bicyclic heterocyclyl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 216, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0419] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 217, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0420] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,7-dimethylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 218, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0421] In some embodiments, with respect to formula (V), A is a bicyclic heterocyclyl (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 219, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0422] In some embodiments, in formula (V), A is a monocyclic heterocyclyl (e.g., pyrazolyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 220, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0423] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 6,8-dimethylimidazo[1,2-a]pyradyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 221, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0424] In some embodiments, for formula (V), A is a bicyclic heterocycline (e.g., 6,8-dimethyl-[1,2,4]triazolo[1,5-a]pyradyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 222, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0425] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 4,6-dimethylpyrazolo[1,5-a]pyradyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 223, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0426] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2-methylimidazo[1,2-a]pyradyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 224, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0427] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 7-fluoro-2-methyl-2H-indazolyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 225, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0428] In some embodiments, for formula (V), A is a bicyclic heterocycline (e.g., 4-fluoro-2-methylbenzo[d]thiazolyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is C(R6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 226, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0429] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 247, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0430] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 248, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0431] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 7-fluoro-2-methyl-2H-indazolyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 249, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0432] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 4-fluoro-2-methylbenzo[d]oxazolyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 250, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0433] In some embodiments, with respect to formula (V), A is a bicyclic heterocyclyl (e.g., 2,7-dimethyl-2H-indazolyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 251, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0434] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 252, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0435] In some embodiments, for formula (V), A is a bicyclic heterocycline (e.g., 4-fluoro-2-methylbenzo[d]thiazolyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 253, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0436] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,7-dimethylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 254, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0437] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2-methylimidazo[1,2-a]pyradyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 255, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0438] In some embodiments, with respect to formula (V), A is a bicyclic heterocyclyl (e.g., 8-chloro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 256, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0439] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 257, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0440] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 6,8-dimethylimidazo[1,2-a]pyradyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; and n is 1. In some embodiments, the compound of formula (V) is compound 258, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0441] In some embodiments, for formula (V), A is a bicyclic heterocycline (e.g., 6,8-dimethyl-[1,2,4]triazolo[1,5-a]pyradyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 259, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0442] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 4,6-dimethylpyrazolo[1,5-a]pyradyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 260, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0443] In some embodiments, with respect to formula (V), A is a monocyclic heterocyclyl (e.g., pyrazyl); B is a monocyclic heterocyclyl (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 261, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0444] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 262, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0445] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2-methyl-2H-indazolyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 263, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0446] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., pyrrolidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 264, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0447] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 265, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0448] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., N-ethylpiperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 266, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0449] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., 2,2-dimethylpiperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 267, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0450] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 268, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0451] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., pyrrolidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 269, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0452] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., N-ethylpiperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 270, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0453] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., N-methylpyrrolidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 271, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0454] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., 2-methylpiperidine); L 1 and L 2 is nonexistent; Y is N; R 2is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 272, 273, 324, 328, 329, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0455] In some embodiments, with respect to formula (V), A is a bicyclic heterocyclyl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 274, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0456] In some embodiments, with respect to formula (V), A is a bicyclic heterocyclyl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocyclyl (e.g., tetrahydro-2H-pyranyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 275, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0457] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 8-fluoro-2-methylimidazo[1,2-a]pyridinyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(for example, CH) and; R 2is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 276, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0458] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., N-methyl2-methylpiperidine); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 277, 278, 325, 330, 331, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0459] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., 2,2-dimethylpiperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 279, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0460] In some embodiments, with respect to formula (V), A is a bicyclic heterocyclyl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocyclyl (e.g., 8-azabicyclo[3.2.1]octanyl); L 1 and L 2 is nonexistent; Y is N; R 2is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 280, 326, 332, 333, 334, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0461] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., 2-methylpiperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 281, 327, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0462] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., N-methylpyrrolidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(R 6b )(for example, CH2); each R 2 is hydrogen; m is 0; n is 2. In some embodiments, the compound of formula (V) is compound 282, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0463] In some embodiments, with respect to formula (V), A is a bicyclic heterocyclyl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocyclyl (e.g., azepanil); L 1 and L 2 is nonexistent; Y is N; R 2is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 283, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0464] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., 2-ethylpiperidinyl); L 1 and L 2 is nonexistent; Y is N; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 304, 305, 328, 335, 336, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0465] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., piperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(for example, CH) and; R 2 is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 309, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0466] In some embodiments, with respect to formula (V), A is a bicyclic heterocycline (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocycline (e.g., N-methylpiperidinyl); L 1 and L 2 is nonexistent; Y is C(R 6a )(for example, CH) and; R 2is hydrogen; m is 0; n is 1. In some embodiments, the compound of formula (V) is compound 310, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0467] In some embodiments, with respect to formula (V), A is a bicyclic heterocyclyl (e.g., 2,8-dimethylimidazo[1,2-b]pyridazyl); B is a monocyclic heterocyclyl (e.g., 4-azaspiro[2.5]octanyl); L 1 and L 2 is nonexistent; Y is N; R 2 R is hydrogen; 3 is a halo (e.g., F); m is 1; and n is 1. In some embodiments, the compound of formula (V) is compound 312, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

[0468] Pharmaceutical composition, kit, and administration The present invention provides a pharmaceutical composition comprising a compound of formula (I), (III), or (V), for example, a compound of formula (I), (III), or (V) as described herein, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, and optionally a pharmaceutically acceptable additive. In certain embodiments, the pharmaceutical composition described herein comprises a compound of formula (I), (III), or (V), or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable additive. In certain embodiments, the compound of formula (I), (III), or (V), 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.

[0469] The pharmaceutical compositions described herein can be prepared by any method known in the art of pharmacology. Generally, such preparation methods include the steps of combining a compound of formula (I), (III), or (V) ("active ingredient") with a carrier and / or one or more other auxiliary components, and then, if necessary and / or desirable, shaping and / or packaging the product into desired single-dose or multi-dose units.

[0470] Pharmaceutical compositions may be prepared, packaged, and / or sold in a single unit dose and / or as multiple single unit doses. As used herein, “unit dose” refers to a separate amount of a pharmaceutical composition containing a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dose of the active ingredient administered to a subject and / or a convenient fraction of such dose, for example, half or one-third of such dose.

[0471] The relative amounts of the active ingredient, pharmaceutically acceptable additives, and / or any further components in the pharmaceutical composition of the present invention vary depending on the identity, size, and / or state of the object being treated, and further on the route through which the composition is administered. For example, the composition may contain 0.1% to 100% (w / w) of the active ingredient.

[0472] The term "pharmaceutically acceptable additive" refers to a non-toxic carrier, adjuvant, excipient, or vehicle that does not impair the pharmacological activity of the compound formulated with it. Pharmacochemically acceptable additives useful in the manufacture of the pharmaceutical compositions of the present invention are any known in the art of pharmaceutical formulation and include inert excipients, dispersants and / or granulators, surfactants and / or emulsifiers, disintegrants, binders, preservatives, buffers, lubricants, and / or oils. pharmaceutically acceptable additives useful in the production of the 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, buffering substances, such as phosphates, glycine, sorbic acid, potassium sorbate, partially 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, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylate, wax, polyethylene-polyoxypropylene-block polymer, polyethylene glycol, and lanolin.

[0473] The compositions of the present invention may be administered orally, parenterally (including subcutaneous, intramuscular, intravenous, and intradermal), by inhalation spray, topically, rectally, transnasally, intraoral buccally, transvaginally, or via an implanted reservoir. In some embodiments, the compounds or compositions provided may be administered intravenously and / or orally.

[0474] The term “parenteral” as used herein includes injection or infusion techniques such as subcutaneous, intravenous, intramuscular, intraocular, intravitreous, intraarticular, intrabursal, intrasternal, subarachnoid, intrahepatic, intraperitoneal, intrafocal, and intracranial. Preferably, the composition is administered orally, subcutaneously, intraperitoneally, or intravenously. The sterile injectable form of the composition of the present invention may be an aqueous or oily suspension. These suspensions may be formulated by techniques known in the art using appropriate dispersing or wetting and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable excipient or solvent, for example, a solution in 1,3-butanediol. Acceptable vehicles and solvents that may be used include water, Ringer's solution, and isotonic saline. Furthermore, sterile non-volatile oils have been conventionally used as solvents or suspensions.

[0475] The pharmaceutically acceptable compositions of the present invention may be administered orally 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 corn starch. Lubricants, such as magnesium stearate, are also typically added. For oral administration in capsule form, useful excipients include lactose and dried corn starch. When aqueous suspensions are required for oral use, the active ingredient is combined with an emulsifier and a suspending agent. Certain sweeteners, flavorings, or colorings may also be added as needed. In some embodiments, the oral formulations provided are formulated for immediate release or sustained / delayed release. In some embodiments, the compositions are suitable for oral buccal or sublingual administration, including tablets, lozenges, and flavored tablets. The compounds provided may also be in microencapsulated form.

[0476] Alternatively, the pharmaceutically acceptable compositions of the present invention may be administered in the form of suppositories for rectal administration. The pharmaceutically acceptable compositions of the present invention may also be administered topically, particularly when the target of treatment includes areas or organs that are readily accessible by topical application, including diseases of the eyes, skin, or lower intestinal tract. Appropriate topical formulations are readily prepared for each of these areas or organs.

[0477] For use in the eyes, the pharmaceutically acceptable compositions provided may be formulated as a micronized suspension or in an ointment, for example, in petrolatum.

[0478] To prolong the effects of a drug, it is often desirable to slow down the absorption of the drug from subcutaneous or intramuscular injection. This can be achieved by using a liquid suspension of a crystalline or amorphous material with poor water solubility. The rate of drug absorption is determined by its rate of dissolution, which may be determined by the crystal size and morphology. Alternatively, delayed absorption of parenterally administered drug forms is achieved by dissolving or suspending the drug in an oil vehicle.

[0479] The descriptions of pharmaceutical compositions provided herein primarily concern pharmaceutical compositions suitable for administration to humans, but those skilled in the art will understand that such compositions are generally suitable for administration to all types of animals. Modifications of pharmaceutical compositions suitable for administration to humans to make them suitable for administration to various animals are well understood, and a normally skilled veterinary pharmacologist can design and / or perform such modifications using conventional experimental methods.

[0480] The compounds provided herein are typically formulated in dose-unit forms, e.g., single-unit dosage forms, for ease of administration and uniformity of dosage. However, it is understood that the total daily dose of the compositions of the present invention should be determined by the attending physician within the bounds of sound medical judgment. A specific therapeutically effective dose level for any particular subject or organism depends on a variety of factors, including: the severity of the disease or disorder being treated; the activity of the specific active ingredient used; the specific composition used; the subject's age, weight, overall health, sex, and diet; the timing, route of administration, and excretion rate of the specific active ingredient used; the duration of treatment; drugs used in combination with or concurrently with the specific active ingredient used; and similar factors well known in the art of medicine.

[0481] The exact amount of compound required to achieve an effective dose varies depending on the subject, for example, the species, age, and general condition of the subject, the severity of side effects or disorders, the identity of the specific compound, and the mode of administration. The desired dose can be delivered three times a day, twice a day, once a day, every other day, every two days, weekly, every two weeks, every three weeks, or every four weeks. In certain embodiments, the desired dose can be delivered using multiple doses (e.g., two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, or more doses).

[0482] In a particular embodiment, an effective dose of the compound for once or multiple daily administration to a 70 kg adult human may contain, per unit dosage form, 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.

[0483] In certain embodiments, the compound of formula (I), (III), or (V) may be at a dose level sufficient to deliver 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 (body weight of the subject) (once or more times per day) in order to obtain the desired therapeutic effect.

[0484] It should be recognized that the dose ranges described herein are intended to provide guidance for the administration of the pharmaceutical compositions provided to adults. For example, the amount administered to children or adolescents may be determined by a practitioner or a person skilled in the art and may be lower or the same as that administered to adults.

[0485] It is also recognized that compounds or compositions described herein may be administered in combination with one or more further pharmaceuticals. These compounds or compositions may be administered in combination with further pharmaceuticals that improve their bioavailability, reduce and / or modify their metabolism, inhibit their excretion, and / or modify their distribution in the body. It should also be understood that the treatments used may achieve the desired effect for the same disorder, and / or different effects.

[0486] The compound or composition may be administered, for example, in conjunction with, before, or after, one or more further pharmaceuticals that may be useful as combination therapy. The pharmaceuticals may include a therapeutic activator. The pharmaceuticals may also include a prophylactic activator. Each further pharmaceutical may be administered in a dose and / or time schedule determined for that pharmaceutical. The further pharmaceuticals may also be administered together in a single dose and / or together with the compounds or compositions described herein, or separately in different doses. The specific combination used in a regimen will take into account the compatibility of the compounds of the present invention with the further pharmaceuticals, and / or the desired therapeutic and / or prophylactic effects to be achieved. Generally, further pharmaceuticals used in combination are expected to be used at a level that does not exceed the level at which they are used individually. In some embodiments, the level at which they are used in combination is lower than the level at which they are used individually.

[0487] Further exemplary pharmaceuticals include, but are not limited to, antiproliferative agents, anticancer agents, antidiabetic agents, anti-inflammatory agents, immunosuppressants, and analgesics. Pharmaceuticals include small organic molecules, such as drug compounds (e.g., compounds approved by the U.S. Food and Drug Administration, as provided in the Code of Federal Regulations (CFR)), peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNA, RNA, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, lipids, hormones, vitamins, and cells.

[0488] Also encompassed by the present invention are kits (e.g., pharmaceutical packs). Kits of the present invention may be useful for preventing and / or treating proliferative or nonproliferative disorders, for example, as described herein. The kits provided may comprise the pharmaceutical composition or compound of the present invention and a container (e.g., vials, ampoules, bottles, syringes, and / or dispenser packages, or other suitable containers). In some embodiments, the kits provided may optionally further comprise a second container containing pharmaceutical additives for dilution or suspension of the pharmaceutical composition or compound of the present invention. In some embodiments, the container and the pharmaceutical composition or compound of the present invention provided in the second container combine to form a single dosage form.

[0489] Thus, in one embodiment, a kit is provided comprising a first container containing a compound described herein, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or a pharmaceutical composition thereof. In certain embodiments, the kit of the Disclosure comprises a first container containing a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In certain embodiments, the kit is useful in preventing and / or treating a disease, disorder, or condition described herein (e.g., a proliferative disorder or a non-proliferative disorder) in a subject. In certain embodiments, the kit further comprises instructions for administering the compound, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, or a pharmaceutical composition thereof to a subject for the prevention and / or treatment of a proliferative disorder or a non-proliferative disorder.

[0490] How to use This specification describes compounds useful for modulating splicing. In some embodiments, compounds of formula (I), (III), or (V) can be used to increase or decrease splicing at splice sites, thereby altering the quantity, structure, or composition of nucleic acids (e.g., RNA precursors, e.g., premRNA, or thus obtained mRNA). In some embodiments, increasing or decreasing splicing results in a modification of the level or structure of the produced gene product (e.g., RNA or protein). In some embodiments, compounds of formula (I), (III), or (V) can modulate components of a splicing mechanism, for example, by modulating the interaction between components of the splicing mechanism and another entity (e.g., nucleic acids, proteins, or combinations thereof). The splicing mechanisms referred to herein include one or more spliceosome components. The spliceosome components may include, for example, major spliceosome members (U1, U2, U4, U5, U6snRNP) or non-major spliceosome members (U11, U12, U4atac, U6atac snRNP) and one or more of their accessory splicing factors.

[0491] In another embodiment, the disclosure features a method for modifying a target (e.g., an RNA precursor, e.g., premRNA) by including a splice site in the target, wherein the method includes providing a compound of formula (I), (III), or (V). In some embodiments, including a splice site in the target (e.g., an RNA precursor, e.g., premRNA, or the mRNA thus obtained) results in the addition or deletion of one or more nucleic acids to the target (e.g., a novel exon, e.g., a skipped exon). The addition or deletion of one or more nucleic acids to the target may result in an increase in the level of the gene product (e.g., RNA, e.g., mRNA, or protein).

[0492] In another embodiment, the disclosure features a method for modifying a target (e.g., an RNA precursor, e.g., premRNA, or mRNA thus obtained) by eliminating a splice site in the target, wherein the method includes providing compounds of formula (I), (III), or (V). In some embodiments, eliminating a splice site in the target (e.g., an RNA precursor, e.g., premRNA) results in the deletion or addition of one or more nucleic acids from the target (e.g., skipped exons, e.g., novel exons). The deletion or addition of one or more nucleic acids from the target may result in a reduction in the level of the gene product (e.g., RNA, e.g., mRNA, or protein). In other embodiments, methods for modifying a target (e.g., an RNA precursor, e.g., premRNA, or mRNA thus obtained) include, for example, suppression of splicing at the splice site or enhancement of splicing at the splice site (e.g., more than about 0.5%, e.g., 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or more) compared to a reference (e.g., in the absence of a compound of formula (I), (III), or (V), or in healthy or abnormal cells or tissue).

[0493] The methods described herein can be used, for example, to modify the splicing of nucleic acids containing a specific sequence (e.g., a target sequence). Exemplary genes encoding a target sequence (e.g., DNA or RNA, e.g., a target sequence containing premRNA) include, in particular, ABCA4, ABCA9, ABCB1, ABCB5, ABCC9, ABCD1, ACADL, ACADM, ACADSB, ACSS2, ACTB, ACTG2, ADA, ADAL, ADAM10, ADAM15, ADAM22, ADAM32, ADAMTS12, ADAMTS13, ADAMTS20, ADAMTS6, ADAMTS9, ADAR, ADCY3, ADCY10, ADCY8, ADNP, ADRBK2, AFP, AGL, AGT, AHCTF1, AHR, AKAP10, AKAP3, AKNA, ALAS1, ALS2CL, ALB, ALDH3A2, ALG6, AMBRA1, ANK3, and ANTXR2. , ANXA10, ANXA11, ANGPTL3, AP2A2, AP4E1, APC, APOA1, APOB, APOC3, APOH, AR, ARID2, ARID3A, ARID3B, ARFGEF1, ARFGEF2, ARHGAP1, ARHGAP8, ARHGAP18, ARHGAP26, ARHGEF18, ARHGEF2, ARPC3, ARS2, ASH1L , ASH1L-IT1, ASNSD1, ASPM, ATAD5, ATF1, ATG4A, ATG16L2, ATM, ATN1, ATP11C, ATP6V1G3, ATP13A5, AT P7A, ATP7B, ATR, ATXN2, ATXN3, ATXN7, ATXN10, AXIN1, B2M, B4GALNT3, BBS4, BCL2, BCL2L1, BCL2-like 11(BIM), BCL11B, BBOX1, BCS1L, BEAN1, BHLHE40, BMPR2, BMP2K, BPTF, BRAF, BRCA1, BRCA2, BRCC3, BRSK1, BRSK2, BTAF1, BTK, C2orf55, C4orf29, C6orf118, C9orf43, C9orf72, C10orf137, C11orf30, C11orf65, C11orf70, C11οrf87, C12orf51, C13or f1, C13orf15, C14orf10l, C14orf118, C15orf29, C15orf42, C15orf60, C16orf33,C16orf38、C16orf48、C18orf8、C19orf42、C1orf107、C1orf114、C1orf130、 C1orf149、C1orf27、C1orf71、C1orf94、C1R、C20orf74、C21orf70、C3orf23 、C4orf18、C5orf34、C8B、C8orf33、C9orf114、C9orf86、C9orf98、C3、CA11、 CAB39、CACHD1、CACNA1A、CACNA1B、CACNA1C、CACNA2D1、CACNA1G、CACNA1H、C ALCA、CALCOCO2、CAMK1D、CAMKK1、CAPN3、CAPN9、CAPSL、CARD11、CARKD、CAS Z1、CAT、CBLB、CBX1、CBX3、CCDC102B、CCDC11、CCDC15、CCDC18、CCDC5、CCDC 81、CCDC131、CCDC146、CD4、CD274、CD1B、CDC14A、CDC16、CDC2L5、CDC42BPB 、CDCA8、CDH10、CDH11、CDH24、CDH8、CDH9、CDK5RAP2、CDK6、CDK8、CDK11B、CD 33、CD46、CDH1、CDH23、CDK6、CDK11B、CDK13、CEBPZ、CEL、CELSR3、CENPA、CE NPI、CENPT、CENTB2、CENTG2、CEP110、CEP170、CEP192、CETP、CFB、CFTR、CFH 、CGN、CGNL1、CHAF1A、CHD9、CHIC2、CHL1、CHN1、CHM、CLEC16A、CL1C2、CLCN1 、CLINT1、CLK1、CLPB、CLPTM1、CMIP、CMYA5、CNGA3、CNOT1、CNOT7、CNTN6、COG 3、COL11A1、COL11A2、COL12A1、COL14A1、COL15A1、COL17A1、COL19A1、COL1 A1、COL1A2、COL2A1、COL3A1、COL4A1、COL4A2、COL4A5、COL4A6、COL5A2、COL6 A1、COL7A1、COL9A1、COL9A2、COL22A1、COL24A1、COL25A1、COL29A1、COLQ、C OMTD1、COPA、COPB2、COPS7B、COPZ2、CPSF2、CPXM2、CR1、CRBN、CRYZ、CREBBP、CRKRS、CSE1L、CSTB、CSTF3、CT45-6、CTNNB1、CUBN、CUL4B、CUL5、CXorf41、C XXC1、CYBB、CYFIP2、CYP3A4、CYP3A43、CYP3A5、CYP4F2、CYP4F3、CYP17、CYP 19, CYP24A1, CYP27A1, DAB1, DAZ2, DCBLD1, DCC, DCTN3, DCUN1D4, DDA1, DDEF1, DDX1, DDX24, DDX4, DENND2D, DEPDC2, DES, DGAT2, DHFR, DHRS7, DHRS9, DH X8, DIP2A, DMD, DMTF1, DNAH3, DNAH8, DNAI1, DNAJA4, DNAJC13, DNAJC7, DNM T1、DNTTIP2、DOCK4、DOCK5、DOCK10、DOCK11、DOT1L、DPP3、DPP4、DPY19L2P2、 DR1、DSCC1、DVL3、DUX4、DYNC1H1、DYSF、E2F1、E2F3、E2F8、E4F1、EBF1、EBF3 、ECM2、EDEM3、EFCAB3、EFCAB4B、EFNA4、EFTUD2、EGFR、EIF3A、ELA1、ELA2A、E LF2、ELF3、ELF4、EMCN、EMD、EML5、ENO3、ENPP3、EP300、EPAS1、EPB41L5、EPH A3、EPHA4、EPHB1、EPHB2、EPHB3、EPS15、ERBB4、ERCC1、ERCC8、ERGIC3、ERMN、 ERMP1, ERN1, ERN2, ESR1, ESRRG, ETS2, ETV3, ETV4, ETV5, ETV6, EVC2, EWSR1, EXO1, EXOC4, F3, F11, F13A1, F5, F7, F8, FAH, FAM13A1, FAM13B1, FAM13C1, F AM134A, FAM161A, FAM176B, FAM184A, FAM19A1, FAM20A, FAM23B, FAM65C, FANCA, FANCC, FANCG, FANCM, FANK1, FAR2, FBN1, FBXO15, FBXO18, FBXO38, FCGB P、FECH、FEZ2、FGA、FGD6、FGFR2、FGFR1OP、FGFR1OP2、FGFR2、FGG、FGR、FIX、 FKBP3、FLI1、FLJ35848、FLJ36070、FLNA、FN1、FNBP1L、FOLH1、FOSL1、FOSL2、FOXK1, FOXM1, FOXO1, FOXP4, FRAS1, FUT9, FXN, FZD3, FZD6, GAB1, GABPA, GALC, GALNT3, GAPDH, GART, GAS2L3, GATA3, GATAD2A, GBA, GBGT1, GCG, GCGR, G CK、GFI1、GFM1、GH1、GHR、GHV、GJA1、GLA、GLT8D1、GNA11、GNAQ、GNAS、GNB5、 GOLGB1、GOLT1A、GOLT1B、GPATCH1、GPR158、GPR160、GPX4、GRAMD3、GRHL1、GR HL2, GRHPR, GRIA1, GRIA3, GRIA4, GRIN2B, GRM3, GRM4, GRN, GSDMB, GSTCD, GSTO2, GTF2I, GTPBP4, HADHA, HAND2, HBA2, HBB, HKK, HDAC3, HDAC5, HDX, HEP ACAM2、HERC1、HES7、HEXA、HEXB、HHEX、HIPK3、HLA-DPB1、HLA-G、HLCS、HLTF 、HMBS、HMGA1、HMGCL、HNF1A、HNF1B、HNF4A、HNF4G、HNRNPH1、HOXC10、HP1BP3 、HPGD、HPRT1、HPRT2、HSF1、HSF4、HSF2BP、HSPA9、HSPG2、HTT、HXA、ICA1、ID H1、IDS、IFI44L、IKBKAP、IKZF1、IKZF3、IL1R2、IL5RA、IL7RA、IMMT、INPP5D 、INSR、INTS3、INTU、IP04、IP08、IQGAP2、IRF2、IRF4、IRF8、IRX3、ISL1、ISL 2、ITFG1、ITGA6、ITGAL、ITGB1、ITGB2、1TGB3、ITGB4、ITIH1、ITPR2、IWS1、JA K1、JAK2、JAG1、JMJD1C、JPH3、KALRN、KAT6A、KATNAL2、KCNN2、KCNT2、KDM2A 、KIAA0256、KIAA0528、KIAA0564、KIAA0586、KIAA1033、KIAA1166、KIAA121 9, KIAA1409, KIAA1622, KIAA1787, KIF3B, KIF15, KIF16B, KIF5A, KIF5B, KIF9, KIN, KIR2DL5B, KIR3DL2, KIR3DL3, KIT, KLF3, KLF5, KLF7, KLF10, KLF12KLF16、KLHL20、KLK12、KLKB1、KMT2A、KMT2B、KPNA5、KRAS、KREMEN1、KRIT1、 KRT5、KRTCAP2、KYNU、L1CAM、L3MBTL、L3MBTL2、LACE1、LAMA1、LAMA2、LAMA3、 LAMB1、LARP7、LDLR、LEF1、LENG1、LGALS3、LGMN、LHCGR、LHX3、LHX6、LIMCH1 、LIMK2、LIN28B、LIN54、LMBRD1、LMBRD2、LMLN、LMNA、LMO2、LMO7、LOC389634 、LOC390110、LPA、LPCAT2、LPL、LRP4、LRPPRC、LRRK2、LRRC19、LRRC42、LRWD 1、LUM、LVRN、LYN、LYST、MADD、MAGI1、MAGT1、MALT1、MAP2K1、MAP4K4、MAPK8I P3、MAPK9、MAPT、MARC1、MARCH5、MATN2、MBD3、MCF2L2、MCM6、MDGA2、MDM4、A SXL1、FUS、SPR54、MECOM、MEF2C、MEF2D、MEGF10、MEGF11、MEMO1、MET、MGA、MG AM、MGAT4A、MGAT5、MGC16169、MGC34774、MKKS、MIB1、MIER2、MITF、MKL2、ML ANA、MLH1、MLL5、MLX、MME、MPDZ、MPI、MRAP2、MRPL11、MRPL39、MRPS28、MRPS3 5、MS4A13、MSH2、MSH3、MSMB、MST1R、MTDH、MTERF3、MTF1、MTF2、MTIF2、MTHF R、MUC2、MUT、MVK、MYB、MYBL2、MYC、MYCBP2、MYH2、MYRF、MYT1、MY019、MY03A、 MY09B、MYOM2、MYOM3、NAG、NARG1、NARG2、NCOA1、NDC80、NDFIP2、NEB、NEDD4 、NEK1、NEK5、ΝΕΚ11、NF1、NF2、NFATC2、NFE2L2、NFIA、NFIB、NFIX、NFKB1、NFK B2, NFKBIL2, NFRKB, NFYA, NFYB, NIPA2, NKAIN2, NKAP, NLRC3, NLRC5, NLRP3, NLRP7, NLRP8, NLRP13, NME1, NME1-NME2, NME2, NME7, NOL10, NOP561, NOS1NOS2A, NOTCH1, NPAS4, NPM1, NR1D1, NR1H3, NR1H4, NR4A3, NR5A1, NRXN1, NSMAF, NSMCE2, NT5C, NT5C2, NT5C3, NUBP1, NUBPL, NUDT5, NUMA1, NUP88, NUP98, N UP160、NUPL1、OAT、OAZ1、OBFC2A、OBFC2B、OLIG2、OMA1、OPA1、OPN4、OPTN、OSBPL11、OSBPL8、OSGEPL1、OTC、OTX2、OVOL2、OXT、PA2G4、PADI4、PAH、PAN2 PAOX、PAPOLG、PARD3、PARP1、PARVB、PAWR、PAX3、PAX8、PBGD、PBRM1、PBX2、PCBP4、PCCA、PCGF2、PCNX、PCOTH、PDCD4、PDE4D、PDE8B、PDE10A、PD1A3、PDH1、 PDLIM5、PDXK、PDZRN3、PELI2、PDK4、PDS5A、PDS5B、PGK1、PGM2、PHACTR4、PHEX、PHKB、PHLDB2、PHOX2B、PHTF1、PIAS1、PIEZO1、PIGF、PIGN、PIGT、PIK3C2 G、PIK3CA、PIK3CD、PIK3CG、PIK3RI、PIP5K1A、PITRM1、PIWIL3、PKD1、PKHD1L1、PKD2、PKIB、PKLR、PKM1、PKM2、PLAGL2、PLCB1、PLCB4、PLCG1、PLD1、PLEKH A5, PLEKHA7, PLEKHM1, PLKR, PLXNC1, PMFBP1, POLN, POLR3D, POMT2, POSTN, POU2AF1, POU2F2, POU2F3, PPARA, PPFIA2, PPP1R12A, PPP3CB, PPP4C, PPP4R1L, PPP4R2, PRAME, PRC1, PRDM1, PREX1, PREX2, PRIM1, PRIM2, PRKAR1A, PRKCA, PRKG1, PRMT7, PROC, PROCR, PROSC, PRODH, PROX1, PRPF40B, PRPF4B, PRRG 2、PRUNE2、PSD3、PSEN1、PSMAL、PTCH1、PTEN、PTK2、PTK2B、PTPN2、PTPN3、PTPN4、PTPN11、PTPN22、PTPRD、PTPRK、PTPRM、PTPRN2、PTPRT、PUS10、PVRL2、PY GM、QRSL1、RAB11FIP2、RAB23、RAF1、RALBP1、RALGDS、RB1CC1、RBL2、RBM39、RBM45、RBPJ、RBSN、REC8、RELB、RFC4、RFT1、RFTN1、RHOA、RHPN2、RIF1、RIT1RLN3、RMND5B、RNF11、RNF32、RNFT1、RNGTT、ROCK1、ROCK2、RORA、RP1、RP6KA3、RP11~265F1、RP13~36C9、RPAP3、RPN1、RPGR、RPL22、RPL22L1、RP6KA6、R REB1、RRM1、RRP1B、RSK2、RTEL1、RTF1、RUFY1、RUNX1、RUNX2、RXRA、RYR3、SAAL1、SAE1、SALL4、SAT1、SATB2、SBCAD、SCN1A、SCN2A、SCN3A、SCN4A、SCN5A、S CN8A, SCNA, SCN11A, SCO1, SCYL3, SDC1, SDK1, SDK2, SEC24A, SEC24D, SEC31A, SEL1L, SENP3, SENP6, SENP7, SERPINA1, SETD3, SETD4, SETDB1, SEZ6, SFRS12, SGCE, SGOL2, SGPL1, SH2D1A, SH3BGRL2, SH3PXD2A, SH3PXD2B, SH3RF2, SH3TC2, SHOC2, SIPA1L2, SIPA1L3, SIVA1, SKAP1, SKIV2L2, SLC6A11, SLC6A1 3、SLC6A6、SLC7A2、SLC12A3、SLC13A1、SLC22A17、SLC25A14、SLC28A3、SLC33A1、SLC35F6、SLC38A1、SLC38A4、SLC39A10、SLC4A2、SLC6A8、SMARCA1、SMA RCA2、SMARCA5、SMARCC2、SMC5、SMN2、SMOX、SMS、SMTN、SNCAIP、SNORD86、SNRK、SNRP70、SNX5、SNX6、SOD1、SOD10、SOS、SOS2、SOX5、SOX6、SOX8、SP1、SP2、 SP3、SP110、SPAG9、SPATA13、SPATA4、SPATS1、SPECC1L、SPDEF、SPI1、SPINK5、SPP2、SPTA1、SRF、SRM、SRP72、SSX3、SSX5、SSX9、STAG1、STAG2、STAMBPLI、 STARD6、STAT1、STAT3、STAT5A、STAT5B、STAT6、STK17B、STX3、STXBP1、SUCLG2、SULF2、SUPT6H、SUPT16H、SV2C、SYCP2、SYT6、SYCPI、SYTL3、SYTL5、TAF2、TARDBP、TBC1D3G、TBC1D8B、TBC1D26、TBC1D29、TBCEL、TBK1、TBP、TBPL1、TB R1、TBX、TCEB3、TCF3、TCF4、TCF7L2、TCFL5、TCF12、TCP11L2、TDRD3、TEAD1、T EAD3, TEAD4, TECTB, TEK, TERF1, TERF2, TET2, TFAP2A, TFAP2B, TFAP2C, TFAP4, TFDP1, TFRC, TG, TGM7, TGS1, THAP7, THAP12, THOC2, TIAL1, TIAM2, TIMM5 0、TLK2、TM4SF20、TM6SF1、TMEM27、TMEM77、TMEM156、TMEM194A、TMF1、TMPR SS6、TNFRSF10A、TNFRSF10B、TNFRSF8、TNK2、TNKS、TNKS2、TOM1L1、TOM1L2、T OP2B、TP53、TP53INP1、TP53BP2、TP53I3、TP63、TRAF3IP3、TRAPPC2、TRIM44 、TRIM65、TRIML1、TRIML2、TRPM3、TRPM5、TRPM7、TRPS1、TSC1、TSC2、TSHB、TS PAN7、TTC17、TTF1、TTLL5、TTLL9、TTN、TTPAL、TTR、TUSC3、TXNDC10、UBE3A、 UCK1、UGT1A1、UHRF1BP1、UNC45B、UNC5C、USH2A、USF2、USP1、USP6、USP18、US P38、USP39、UTP20、UTP15、UTP18、UTRN、UTX、UTY、UVRAG、UXT、VAPA、VEGFA、 VPS29、VPS35、VPS39、VT11A、VT11B、VWA3B、WDFY2、WDR16、WDR17、WDR26、WDR 44, WDR67, WDTC1, WRN, WRNIP1, WT1, WWC3, XBP1, XRN1, XRN2, XX-FW88277, YAP1, YARS, YBX1, YGM, YY1, ZBTB18, ZBTB20, ZC3HAV1, ZC3HC1, ZC3H7A, ZDHHC 19、ZEB1、ZEB2、ZFPM1、ZFYVE1、ZFX、ZIC2、ZNF37A、ZNF91、ZNF114、ZNF155、 ZNF169、ZNF205、ZNF236、ZNF317、ZNF320、ZNF326、ZNF335、ZNF365、ZNF367、This includes ZNF407, ZNF468, ZNF506, ZNF511, ZNF511-PRAP1, ZNF519, ZNF521, ZNF592, ZNF618, ZNF763, and ZWINT.

[0494] Further exemplary genes encoding target sequences (e.g., DNA or RNA containing the target sequence, e.g., premRNA) include A1CF, A4GALT, AAR2, ABAT, ABCA11P, ZNF721, ABCA5, ABHD10, ABHD13, ABHD2, ABHD6, AC000120.3, KRIT1, AC004076.1, ZNF772, AC004076.9, ZNF772, AC004223.3, RAD51D, AC004381.6, AC006486.1, and ERF. , AC007390.5, AC007780.1, PRKAR1A, AC007998.2, INO80C, AC009070.1, CMC2, AC009879.2, AC009879.3, ADHFE1, AC010487.3, ZNF816 -ZNF321P, ZNF816, AC010328.3, AC010522.1, ZNF587B, AC010547.4, ZNF19, AC012313.3, ZNF497, AC012651.1, CAPN3, AC013489.1, DE T1, AC016747.4, C2orf74, AC020907.6, FXYD3, AC021087.5, PDCD6, AHRR, AC022137.3, ZNF761, AC025283.3, NAA60, AC027644.4, RAB GEF1, AC055811.2, FLCN, AC069368.3, ANKDD1A, AC073610.3, ARF3, AC074091.1, GPN1, AC079447.1, LIPT1, AC092587.1, AC079594.2, TRIM59, AC091060.1, C18orf21, AC092143.3, MC1R, AC093227.2, ZNF607, AC093512.2, ALDOA, AC098588.1, ANAPC10, AC107871.1, CAL ML4, AC114490.2, ZMYM6, AC138649.1, NIPA1, AC138894.1, CLN3, AC139768.1, AC242426.2, CHD1L, ACADM, ACAP3, ACKR2, RP11~141M3.5、KRBOX1、ACMSD、ACOT9、ACP5、ACPL2、ACSBG1、ACSF2、ACSF3、ACSL1、ACSL3、ACVR1、ADAL、ADAM29、ADAMTS10、ADAMTSL5、ADARB1、ADAT2、ADCK3、ADD3、ADGRG1、ADGRG2、ADH1B、ADIPOR1、ADNP、ADPRH、AGBL5、AGPAT1、AGPAT3、AGR2、AGTR1、AHDC1、AHI1、AH NAK、AIFM1、AIFM3、AIMP2、AK4、AKAP1、AKNAD1、CLCC1、AKR1A1、AKT1、AKT1S1、AKT2、AL139011.2、PEX19、AL157935.2、ST6GAL NAC6、AL358113.1、TJP2、AL441992.2、KYAT1、AL449266.1、CLCC1、AL590556.3、LINC00339、CDC42、ALAS1、ALB、ALDH16A1、ALD H1B1、ALDH3A1、ALDH3B2、ALDOA、ALKBH2、ALPL、AMD1、AMICA1、AMN1、AMOTL2、AMY1B、AMY2B、ANAPC10、ANAPC11、ANAPC15、ANG、 RNASE4、AL163636.2、ANGEL2、ANGPTL1、ANKMY1、ANKRD11、ANKRD28、ANKRD46、ANKRD9、ANKS3、ANKS3,RP11~127I20.7、ANKS6、 ANKZF1、ANPEP、ANXA11、ANXA2、ANXA8L2、AL603965.1、AOC3、AP000304.12、CRYZL1、AP000311.1、CRYZL1、AP000893.2、RAB30 、AP001267.5、ATP5MG、AP002495.2、AP003175.1、OR2AT4、AP003419.1、CLCF1、AP005263.1、ANKRD12、AP006621.5、AP006621.1, AP1G1, AP3M1, AP3M2, APBA2, APBB1, APLP2, APOA2, APOL1, APOL3, APTX, ARAP1, STARD10, ARF4, ARFIP1, ARFIP2, ARFRP1, AHRGAP11A, AHRGAP33, AHRGAP4, AHRGEF10, AHRGEF3, AHRGEF35, OR2A1-AS1, AHRGEF35, OR2A1-AS1, AHRGEF34P, ARID1B, AHRGEF35, OR2A20P, OR2A1-AS1, AHRGEF9, AR L1, ARL13B, ARL16, ARL6, ARMC6, ARMC8, ARMCX2, ARMCX5, RP4-769N13.6, ARMCX5-GPRASP2, BHLHB9, ARMCX5-GPRASP2, GPRASP1, ARMCX5-GPRASP2, GPRASP2, ARMCX6, ARNT2, ARPP19, ARRB2, ARSA, ART3, ASB3, GPR75-ASB3, ASCC2, ASNS, AC079781.5, ASPSCRI1, ASS1, ASUN, ATE1, ATF1, ATF 7IP2、ATG13、ATG4D、ATG7、ATG9A、ATM、ATOX1、ATP1B3、ATP2C1、ATP5F1A 、ATP5G2、ATP5J、ATP5MD、ATP5PF、ATP6AP2、ATP6V0B、ATP6V1C1、ATP6V1D 、ATP7B、ATXN1、ATXN1L,IST1、ATXN3、ATXN7L1、AURKA、AURKB、AXDND1、B 3GALNT1、B3GALT5、AF064860.1、B3GALT5,AF064860.5、B3GNT5、B4GALT3 、B4GALT4、B9D1、BACH1、BAIAP2、BANF1、BANF2、BAX、BAZ2A、BBIP1、BCHE 、BCL2L14、BCL6、BCL9L、BCS1L、BDH1、BDKRB2,AL355102.2、BEST1、BEST3 、BEX4、BHLHB9、BID、BIN3、BIRC2、BIVM、BIVM-ERCC5、BIVM、BLCAP、BLK、 BLOC1S1、RP11~644F5.10、BLOC1S6、AC090527.2、BLOC1S6、RP11~96O20.4、BLVRA、BMF、BOLA1、BORCS8-MEF2B、BORCS8、BRCA1、BRD1、BRDT、BRINP3、BROX、BTBD10、BTBD3、BTBD9、BTD、BTF3L4、BTNL9、BUB1B-PAK6、PAK6、BUB3、C10orf68、C11orf1、C11orf48、C11orf54、C11orf54,AP001273.2、C11orf5 7、C11orf63、C11orf82、C12orf23、C12orf4、C12orf65、C12orf79、C14orf159、C14orf93、C17orf62、C18orf21、 C19orf12、C19orf40、C19orf47、C19orf48、C19orf54、C1D、C1GALT1、C1QB、C1QTNF1、C1S、C1orf101、C1orf112、C 1orf116、C1orf159、C1orf63、C2、C2,CFB、C20orf27、C21orf58、C2CD4D、C2orf15、LIPT1、MRPL30、C2orf80、C2o rf81、C3orf14、C3orf17、C3orf18、C3orf22、C3orf33、AC104472.3、C4orf33、C5orf28、C5orf34、C6orf118、C6orf f203、C6orf211、C6orf48、C7orf50、C7orf55、C7orf55-LUC7L2、LUC7L2、C8orf44-SGK3,C8orf44、C8orf59、C9,D AB2、C9orf153、C9orf9、CA5BP1,CA5B、CABYR、CALCA、CALCOCO1、CALCOCO2、CALM1、CALM3、CALML4、RP11~315D16.2、CALN1、CALU、CANT1、CANX、CAP1、CAPN12、CAPS2、CARD8、CARHSP1、CARNS1、CASC1、CASP3、CASP7、CBFA2T2、CBS、CBY1、CCBL1、CCBL2、RBMXL1、CCDC12、CCDC126、CCDC14、CCDC149、CCDC150、CCDC169-SOHLH2、CCDC169、CCDC171、CCDC37、CCDC41、CCDC57、CCDC63、CCDC7、CCDC74B、CCDC77、CCDC82、CCDC90B、CCDC91、CCDC92、CCNE1、CCHCR1、CCL28、CCNB1IP1、CCNC、CCND3、CCNG1、CCP110、CCR9、CCT7、CCT8、CD151、CD1D、CD200、CD22、CD226、CD276、CD36、CD59、CDC26、CDC42、CDC42SE1、CDC42SE2、CDHR3、CDK10、CDK16、CDK4、CDKAL1、CDKL3,CTD-2410N18.4、CDKN1A、CDKN2A、CDNF、CEBPZOS、CELF1、CEMIP、CENPK、CEP170B、CEP250、CEP57、CEP57L1、CEP63、CERS4、CFL1、CFL2、CFLAR、CGNL1、CHCHD7、CHD1L、CHD8、CHFR,ZNF605、CHIA、CHID1、CHL1、CHM、CHMP1A、CHMP3、RNF103-CHMP3、CHRNA2、CIDEC、CIRBP、CITED1、CKLF-CMTM1、CMTM1、CKMT1B、CLDN12,CTB-13L3.1、CLDND1,AC021660.3、CLDND1,CPOX、CLHC1、CLIP1、CLUL1、CMC4、MTCP1、CNDP2、CNFN、CNOT1、CNOT6、CNOT7、CNOT8、CNR1、CNR2、CNTFR、CNTRL、COA1、COASY、COCH、COL8A1、COLCA1、COLEC11、COMMD3-BMI1、BMI1、COPS5、COPS7B、COQ8A、CORO6、COTL1、COX14,RP4~605O3.4、COX7A2、COX7A2L、COX7B2、CPA4、CPA5、CPEB1、CPNE1、AL109827.1、RBM12、CPNE1、RP1~309K20.6、RBM12、CPNE3、CPSF3L、CPT1C、CREB3L2、CREM、CRP、CRYZ、CS,AC073896.1、CS、R P11~977G19.10、CSAD、CSDE1、CSF2RA、CSGALNACT1、CSK、CSNK2A1、CSRNP2、CT45A4、CT45A4,CT45A5、CT45A6、CT BP2、CTCFL、CTD-2116N17.1、KIAA0101、CTD-2349B8.1、SYT17、CTD-2528L19.4、ZNF607、CTD-2619J13.8、ZNF49 7、CTNNA1、CTNNBIP1、CTNND1、CTPS2、CTSB、CTSL、CTTN、CUL2、CUL9、CWC15、CXorf40B、CYB561A3、CYBC1、CYLD、C YP11A1、CYP2R1、CYP4B1、CYP4F22、DAG1、DAGLB,KDELR2、DARS、DBNL、DCAF11、DCAF8,PEX19、DCLRE1C、DCTD、DCT N1、DCTN4、DCUN1D2、DDR1、DDX11、DDX19B、AC012184.2、DDX19B、RP11~529K1.3、DDX25、DDX39B、ATP6V1G2-DDX3 9B, SNORD84, DDX42, DDX60L, DEDD, DEDD2, DEFA1, DEFA1B, DEFA1B, DEFA3, DENND1C, DENND2A, DENND4B, DET1, DGKA, DGKZ, DGLUCY, DHRS4L2, DHRS9, DHX40, DIABLO, AC048338.1, DIAPH1, DICER1, DKKL1, DLG1, DLG3, DLST, DMC1. 、DMKN、DMTF1、DMTN、DNAJC14、DNAJC19、DNAL1、DNASE1L1、DNMT3A、DOC2A、DOCK8、DOK1、DOPEY1、DPAGT1、DPP8、DRAM2、DRD2、DR OSHA、DSN1、DTNA、DTX2、DTX3、DUOX1、DUOXA1、DUS2、DUSP10、DUSP13、DUSP18、DUSP22、DYDC1、DYDC2、DYNLL1、DYNLT1、DYRK1A、D YRK2, DYRK4, RP11~500M8.7, DZIP1L, E2F6, ECHDC1, ECSIT, ECT2, EDC3, EDEM1, EDEM2, MMP24-AS1, RP4~614O4.11, EEF1AKNMT, EEF1D, EFEMP1, EFHC1, EGFL7, EHF, EI24, EIF1AD, EIF2B5, EIF4G1, EIF2B5, POLR2H, EIF3E, EIF3K, EIF4E3, EIF4G1, ELF1, ELMO2, ELMOD1、AP000889.3、ELMOD3、ELOC、ELOF1、ELOVL1、ELOVL7、ELP1、ELP6、EML3、EMP3、ENC1、ENDOV、ENO1、ENPP5、ENTHD2、ENTPD 6、EP400NL、EPB41L1、EPDR1、NME8、EPHX1、EPM2A、EPN1、EPN2、EPN3、EPS8L2、ERBB3、ERC1、ERCC1、ERG、ERI2、ERI2、DCUN1D3、ERL IN2、ERMARD、ERRFI1、ESR2、RP11~544I20.2、ESRRA、ESRRB、ESRRG、ETFA、ETFRF1、ETV1、ETV4、ETV7、EVA1A、EVC2、EVX1、EXD2、EX O5、EXOC1、EXOC2、FAAP24、FABP6、FADS1、FADS2、FAHD2B、FAM107B、FAM111A、FAM111B、FAM114A1、FAM114A2、FAM115C、FAM115C,FAM115D, FAM120B, FAM133B, FAM135A, FAM153A, FAM153B, FAM154B, FAM156A, FAM156B, FAM168B, FAM172A, FAM182B, FAM192A, FAM19A2, FAM200B FAM220A、FAM220A、AC009412.1、FAM222B、FAM227B、FAM234A、AC004754. 1、FAM3C、FAM45A、FAM49B、FAM60A、FAM63A、FAM81A、FAM86B1、FAM86B2、FA NCI、FANK1、FAR2、FAXC、FAXDC2、FBF1、FBH1、FBXL4、FBXO18、FBXO22、FBX O31、FBXO41、FBXO44、FBXO45、FBXW9、FCHO1、FCHSD2、FDFT1、FDPS、FER、F ETUB、FGD4、FGF1、FGFR1、FGFRL1、FGL1、FHL2、FIBCD1、FIGNL1、FIGNL1,D DC、FKBP5、FKRP、FLRT2、FLRT3、FMC1、LUC7L2、FMC1-LUC7L2、FNDC3B、FOLH 1、FOLR1、FOXP1、FOXK1、FOXM1、FOXO1、FOXP4、AC097634.4、FOXRED1、FPR 1、FPR2、FRG1B、FRS2、FTO、FTSJ1、FUK、FUT10、FUT3、FUT6、FXYD3、FZD3、G 2E3、GAA、GABARAPL1、GABPB1、GABRA5、GAL3ST1、GALE、GALNT11、GALNT14 、GALNT6、GAPVD1、GARNL3、GAS2L3、GAS8、GATA1、GATA2、GATA4、GBA、GCNT1 、GDPD2、GDPD5、GEMIN7,MARK4、GEMIN8、GGA3、GGACT、AL356966.1、GGPS1 、GHRL、GID8、GIGYF2、GIMAP8、GIPC1、GJB1、GJB6、GLB1L、GLI1、GLT8D1、GM FG、GMPR2、GNAI2、GNAQ,GNB1、GNB2、GNE、GNG2、GNGT2、GNPDA1、GNPDA2、G OLGA3,CHFR、GOLGA4、GOLPH3L、GOLT1B、GPBP1L1、GPER1、GPR116、GPR141,EPDR1, GPR155, GPR161, GPR56, GPR63, GPR75-ASB3, ASB3, GPR85, GPSM2, GRAMD1B, GRB10, GRB7, GREM2, GRIA2, GSDMB, GSE1, GSN, GSTA4, GSTZ1, GTDC1, GTF2H1, GTF2H4, VARS2, GTF3C2, GUCY1A3, GUCY1B3, GUK1, GULP1, GYPC, GYS1, GZF1, HAGH, HAO2, HAPLN 3、HAVCR1、HAX1、HBG2、AC104389.4、HBG2、AC104389.4、HBE1、HBG2、AC104389.4、HBE1、OR51B5、HBG2、HBE1、AC104389.28、HBS 1L、HCFC1R1、HCK、HDAC2、HDAC6、HDAC7、HDLBP、HEATR4、HECTD4、HEXIM2、HHAT、HHATL、CCDC13、HINFP、HIRA、C22orf39、HIVEP3 、HJV、HKR1、HLF、HMBOX1、HMGA1、HMGB3、HMGCR、HMGN4、HMOX2、HNRNPC、HNRNPD、HNRNPH1、HNRNPH3、HNRNPR、HOMER3、HOPX、HOXA 3、HOXB3、HOXB3,HOXB4、HOXC4、HOXD3、HOXD3、HOXD4、HPCAL1、HPS4、HPS5、HRH1、HS3ST3A1、HSH2D、HSP90AA1、HSPD1、HTT、HUWE 1、HYOU1、IAH1、ICA1L、ICAM2、ICE2、ICK、IDH2、IDH3G、IDS、IFI27、IFI44、IFT20、IFT22、IFT88、IGF2、INS-IGF2、IGF2BP3、IGF BP6、IKKBAP、IKBKB、IL11、IL18BP、IL18RAP、IL1RAP、IL1RL1、IL18R1、IL1RN、IL32、IL4I1、NUP62、AC011452.1、IL4I1、NUP62、CTC-326K19.6, IL6ST, ILVBL, IMMP1L, IMPDH1, INCA1, ING1, INIP, INPP1, INPP5J, INPP5K, INSIG2, INTS11, INTS12, INTS14, IP6K2, IP6K3, IPO11, LRRC70, IQCE, IQGAP3, IRAK4, IRF3, IRF5, IRF6, ISG20, IST1, ISSYNA1, ITFG2, ITBG1BP1, ITBG7, I TIH4、RP5~966M1.6、ITPRIPL1、JADE1、JAK2、JARID2、JDP2、KANK1、KANK1,RP11~31F19.1、KANK2、KANSL1L、KAT6A、KBTBD2 ,AL451062.3、KHNYN、KIAA0040、KIAA0125、KIAA0196、KIAA0226L、PPP 1R2P4、KIAA0391、KIAA0391、AL121594.1、KIAA0391、PSMA6、KIAA0753 、KIAA0895、KIAA0895L、KIAA1191、KIAA1407、KIAA1841、C2orf74、KI F12、KIF14、KIF27、KIF9、KIFC3、KIN、KIRREL1、KITLG、KLC1、APOPT1、A L139300.1、KLC4、KLHDC4、KLHDC8A、KLHL13、KLHL18、KLHL2、KLHL24、 KLHL7、KLK11、KLK2、KLK5、KLK6、KLK7、KNOP1、KRBA2、AC135178.2、KRB A2, RP11~849F2.7, KRIT1, KRT15, ​​KRT8, KTN1, KXD1, KYAT3, RBMXL1, KYNU, L3MBTL1, LACC1, LARGE, LARP4, LARP7, LAT2, LBHD1, LCA5, LCA5L, L CTL、LEPROTL1、LGALS8、LGALS9C、LGMN、LHFPL2、LIG4、LIMCH1、LIMK2 、LIMS2、LINC00921、ZNF263、LIPF、LLGL2、LMAN2L、LMCD1、LMF1、RP11~ 161M6.2、LMO1、LMO3、LOXHD1、LPAR1、LPAR2、LPAR4、LPAR5、LPAR6、LP HN1、LPIN2、LPIN3、LPP、LRFN5、LRIF1、LRMP、LRRC14、LRRC20、LRRC24、 C8orf82、LRRC39、LRRC42、LRRC48、LRRC4C、LRRC8A、LRRC8B、LRRD1、LRTOMT、LRTOMT、AP000812.5、LSM7、LTB4R、LTBP3、LUC7L2、FMC1-LUC7L 2、LUC7L3、LUZP1、LYG1、LYL1、LYPD4、LYPD6B、LYRM1、LYRM5、LYSMD4、M ACC1、MAD1L1、MAD1L1、AC069288.1、MAEA、MAFF、MAFG、MAFK、MAGEA12,CSAG4, MAGEA2, MAGEA2B, MAGEA4, MAGEB1, MAGOHB, MAN2A2, MANBAL, MAOB, MAP2K3, MAP3K7CL, MAP3K8, MAP7, MAP9, MAPK6, MAPK7, MAPK8, MAPKAP1, 10-Mar, 7-Mar, 8-Mar, MARK2, MASP1, MATK, MATR3, MATR3, SNHG4, MB, MBD5, MBNL1, MBOAT7, MCC, M CFD2、MCM9、MCOLN3、MCRS1、MDC1、MDGA2、MDH2、MDM2、ME1、MEAK7、MECR、MED4、MEF2A、MEF2B,BORCS8-MEF2B、MEF2BNB-MEF 2B、MEF2B、MEF2BNB、MEF2C、MEF2D、MEGF10、MEI1、MEIS2、MELK、MET、METTL13、METTL23、MFF、MFN2、MFSD2A、MGST3、MIB2、MI CAL1、MICAL3、MICOS10、NBL1,MICOS10-NBL1、MID1、MINA、MINOS1-NBL1,MINOS1、MIOS、MIPOL1、MIS12、MKLN1、MKNK1、MKN MRO MROH1、MROH7-TTC4、MROH7、MRPL14、MRPL24、MRPL33,BABAM2、MRPL33、BRE、MRPL47、MRPL48、MRPL55、MRRF、MRTFA、MRTFB、 MRVI1、MS4A1、MS4A15、MS4A3、MS4A6E,MS4A7,MS4A14、MSANTD3、MSANTD4、MSH5,MSH5-SAPCD1、MSL2、MSRB3、MSS51、MTCP1,CMC4、MTERF、MTERF1、MTERF3、MTERFD2、MTERFD3、MTF2、MTG2、MTHFD2、MTHFD2L、MTIF2、MTIF3、MTMR10、MTRF1 、MTRR、MTUS2、MUTYH、MVK、MX1、MX2、MYH10、MYL12A、MYB、MYD88、MYL5、MYLIP、MYNN、MYO15A、MYO1B、MYOM2、MZ F1、N4BP2L2、NAA60、NAB1、NAE1、NAGK、NAP1L1、NAP1L4、NAPG、NARFL、NARG2、NAT1、NAT10、NBPF11、WI2~3658N 16.1、NBPF12、NBPF15、NBPF24、NBPF6、NBPF9、NBR1、NCAPG2、NCBP2、NCEH1、NCOA1、NCOA4、NDC1、NDRG1、NDRG, 2、NDRG4、NDST1、NDUFAF6、NDUFB2、NDUFC1、NDUFS1、NDUFS8、NDUFV1、NEDD1、NEIL1、NEIL2、NEK10、NEK11、NEK6、NEK9、NELFA、NEU4、 NFAT5、NFE2、NFE2L2、AC019080.1、NFRKB、NFYA、NFYC、NIF3L1、NIPA2、NKIRAS1、NKX2~1、NLRC3、NME1、NME1-NME2、NME2、NME1-NME2、 NME2、NME4、NME6、NME9、NOD1、NOL10、NOL8、NONO、NPAS1、NPIPA8、RP11~1212A22.1、NPIPB3、NPIPB4、NPIPB9、NPL、NPM1、NPPA、NQO2 、NR1H3、NR2C2、NR2F2、NR4A1、NRDC、NREP、NRF1、NRG4、NRIP1、NSD2、NSDHL、NSG1、NSMCE2、NSRP1、NT5C2、NTF4、NTMT1、NTNG2、NUBP2、 NUCB2、NUDT1、NUDT2、NUDT4、NUF2、NUMBL、NUP50、NUP54、NUP85、NVL、NXF1、NXPE1、NXPE3、OARD1、OAT、OAZ2、OCIAD1、OCLN、ODF2、OG DHL、OGFOD2、AC026362.1、OGFOD2、RP11~197N18.2、OLA1、OPRL1、OPTN、OR2H1、ORAI2、ORMDL1、ORMDL2、ORMDL3、OSBPL2、OSBPL3、OSB PL5、OSBPL9、OSER1、OSGIN1、OSR2、P2RX4、P2RY2、P2RY6、P4HA2、PABPC1、PACRGL、PACSIN3、PADI1、PAIP2、PAK1、PAK3、PAK4、PAK7、P ALB2、PANK2、PAQR6、PARP11、PARVG、PASK、PAX6、PBRM1、PBXIP1、PCBP3、PCBP4、AC115284.1、PCBP4、RP11~155D18.14、RP11~155D18.12、PCGF3、PCGF5、PCNP、PCSK9、PDCD10、PDCD6、AHRR、PDDC1、PDGFRB、PDIA6、PDIK1L、PDLIM7、PDP1、PDPK1、PDPN、PDZD11、PEA15、PEX2、PEX5、PEX5L、PFKM、PFN4、PGAP2、PGAP2、AC090587.2、PGAP3、PGM3、PGPEP1、PHB、PHC2、PHF20、PHF21A、PHF23、PHKB、PHLDB1、PHOSPHO1、PHOSPHO2、KLHL23、PI4KB、PIAS2、PICALM、PIF1、PIGN、PIGO、PIGT、PIK3CD、PILRB、STAG3L5P-PVRIG2P-PILRB、PIP5K1B、PIR、PISD、PIWIL4,FUT4、PKD2、PKIA、PKIG、PKM、PKN2、PLA1A、PLA2G2A、PLA2G5、PLA2G7、PLAC8、PLAGL1、PLD1、PLD3、PLEKHA1、PLEKHA2、PLEKHA6、PLEKHG5、PLIN1、PLS1、PLS3、PLSCR1、PLSCR2、PLSCR4、PLXNB1、PLXNB2、PMP22、PMS1、PNISR、PNKP,AKT1S1、PNMT、PNPLA4、PNPLA8、PNPO、PNRC1、POC1B、POFUT1、POLB、POLD1、POLH、POLI、POLL、POLR1B、POM121、POM121C,AC006014.7、POM121C、AC211429.1、POMC、POMT1、POP1、PORCN、POU5F1、PSORS1C3、PPARD、PPARG、PPHLN1、PPIL3、PPIL4、PPM1A、PPM1B,AC013717.1, PPP1CB, PPP1R11, PPP1R13L, PPP1R26, PPP1R9A, PPP2R2B, PPP3CA, PPP6R 1, PPP6R3, PPT2,PPT2-EGFL8, EGFL8, PPWD1, PRDM2, PRDM8, PRELID3A, PREP L, PRICKLE1, PRKAG1, PRMT2, PRMT5, PRMT7, PROM1, PRPS1, PRPSAP2, PRR14L PRR15L, PRR5,PRR5-ARHGAP8, PRR5L, PRR7, PRRC2B, PRRT4, PRSS50, PRSS4 5. PRSS44, PRUNE, PRUNE1, PSEN1, PSMA2, PSMF1, PSORS1C1, PSPH, PSRC1, PT BP3, PTHLH, PTK2, PTPDC1, PTPRM, PUF60, PUM2, PUS1, PUS10, PXN, PXYLP1 YCR1, QRICH1, R3HCC1L, R3HDM2, RAB17, RAB23, RAB3A, RAB3D,TMEM205, RAB 4B-EGLN2, EGLN2, AC008537.1, RAB5B, RAB7L1, RABL2A, RABL2B, RABL5, RAC GAP1, RAD17, RAD51L3-RFFL, RAD51D, RAD52, RAE1, RAI14, RAI2, RALBP1, RA N, RANGAP1, RAP1A, RAP1B, RAP1GAP, RAPGEF4, RAPGEFL1, RASGRP2, RASSF1 RBCK1, RBM12B, RBM14, RBM4, RBM14-RBM4, RBM23, RBM4, RBM14-RBM4, RBM47 RBM7,AP002373.1, RBM7, RP11~212D19.4, RBMS2, RBMY1E, RBPJ, RBPMS, RB SN, RCBTB2, RCC1, RCC1, SNHG3, RCCD1, RECQL, RELL2, REPIN1, AC073111.3. REPIN1, ZNF775, RER1, RERE, RFWD3, RFX3, RGL2, RGMB, RGS11, RGS3, RGS5, A L592435.1 RHBDD1 RHNO1 TULP3 RHOC AL603832.3 RHOC,RP11~426L16. 10. RHOH, RIC8B, RIMKLB, RIN1, RIPK2, RIT1, RLIM, RNASE4, ANG, AL16、RNASEK、RNASEK-C17orf49、RNF111、RNF123、RNF13、RNF14、RNF185、RNF216、RNF24、RNF32、RNF34、RNF38、RNF4、RNF44、RNH1、RNMT、RNPS1、RO60、ROPN1、ROPN1B、ROR2、RP1~102H19.8、C6orf163、RP1~283E3.8,CDK11A、RP11~120M18.2,PRKAR1A、RP11~133K1.2、PAK6、RP11~164J13.1,CAPN3、RP11~21J18.1、ANKRD12、RP11~322E11.6,INO80C、RP11~337C18.10,CHD1L、RP11~432B6.3、TRIM59、RP11~468E2.4,IRF9、RP11~484M3.5,UPK1B、RP11~517H2.6、CCR6、RP11~613M10.9、SLC25A51、RP11~659G9.3、RAB30、RP11~691N7.6,CTNND1、RP11~849H4.2、RP11~896J10.3、NKX2~1、RP11~96O20.4,SQRDL、RP11~986E7.7、SERPINA3、RP4~769N13.6、GPRASP1、RP4~769N13.6,GPRASP2、RP4~798P15.3、SEC16B、RP5~1021I20.4、ZNF410、RP6~109B7.3、FLJ27365、RPE、RPH3AL、RPL15、RPL17、RPL17-C18orf32,RPL17、RPL23A、RPL36,HSD11B1L、RPP38、RPS20、RPS27A、RPS3A、RPS6KA3、RPS6KC1、RPS6KL1、RPUSD1、RRAGD、RRAS2、RRBP1、RSL1D1、RSRC2、RSRP1、RUBCNL、RUNX1T1、RUVBL2、RWDD1、RWDD4、S100A13,AL162258.1、S100A13,RP1~178F15.5、S100A16、S100A4、S100A3、S100A6、S100PBP、SAA1、SACM1L、SAMD4B、SAR1A、SARAF、SARNP,RP11~762I7.5、SCAMP5、SCAP、SCAPER、SCFD1、SCGB3A2、SCIN、SCML1、SCNN1D、SCO2、S COC、SCRN1、SDC2、SDC4、SEC13、SEC14L1、SEC14L2、SEC22C、SEC23B、SEC2 4C、SEC61G、SEMA4A、SEMA4C、SEMA4D、SEMA6C、SENP7、SEPP1、11-Sep、2-S ep、SERGEF、AC055860.1、SERP1、SERPINA1、SERPINA5、SERPINB6、SERPIN G1、SERPINH1、SERTAD3、SETD5、SFMBT1、AC096887.1、SFTPA1、SFTPA2、S FXN2、SGCD、SGCE、SGK3、SGK3,C8orf44、SH2B1、SH2D6、SH3BP1,Z83844.3 、SH3BP2、SH3BP5、SH3D19、SH3YL1、SHC1、SHISA5、SHMT1、SHMT2、SHOC2、S HROOM1、SIGLEC5,SIGLEC14、SIL1、SIN3A、SIRT2、SIRT6、SKP1、STAT4、AC 104109.3, SLAIN1, SLC10A3, SLC12A9, SLC14A1, SLC16A6, SLC1A2, SLC1A6, SLC20A2, SLC25A18, SLC25A19, SLC25A22, SLC25A25, SLC25A29, SLC2 5A30, SLC25A32, SLC25A39, SLC25A44, SLC25A45, SLC25A53, SLC26A11, SLC26A4, SLC28A1, SLC29A1, SLC2A14, SLC2A5, SLC2A8, SLC35B2, SLC35B3 SLC35C2, SLC37A1, SLC38A1, SLC38A11, SLC39A13, SLC39A14, SLC41A3, SLC44A3, SLC4A7, SLC4A8, SLC5A10, SLC5A11, SLC6A1, SLC6A12, SLC6A9 、SLC7A2、SLC7A6、SLC7A7、SLCO1A2、SLCO1C1、SLCO2B1、SLFN11、SLFN12、 SLFNL1、SLMO1、SLTM、SLU7、SMAD2、SMAP2、SMARCA2、SMARCE1、AC073508.2、SMARCE1、KRT222、SMC6、SMG7、SMIM22、SMOX、SMPDL3A、SMTN、SMU1、SMUG1、SNAP25、SNCA、SNRK、SNRPC、SNRPD1、SNRPD2、SNRPN、SNRPN、SNURF、SNUPN、SNX11、SNX16、SNX17、SOAT1、SOHLH2、CCDC169-SOHLH2、CCDC169、SORBS1、SORBS2、SOX5、SP2、SPART、SPATA20、SPATA21、SPATS2、SPATS2L、SPDYE2、SPECC1、SPECC1L、SPECC1L-ADORA2A、SPECC1L-A...

Claims

1. Compound of formula (V-a) 【Chemistry 671】 or its pharmaceutically acceptable salts, solvates, hydrates, tautomers, or stereoisomers. [In the formula: A is one or more R １ It is a nitrogen-containing heteroaryl that is optionally substituted with; B is one or more R １ It is a nitrogen-containing heterocycline that is optionally substituted; L １ and L ２ Each of these is independently non-existent, -N(R) ４ )C(O)-, or -C(O)N(R ４ ) - and; Y is N, where the dashed lines in the ring containing Y may be single or double bonds as the valence allows; Each R １ is, independently, hydrogen, C １ to C ６ -alkyl, C ２ to C ６ -alkenyl, C ２ to C ６ -alkynyl, C １ to C ６ -heteroalkyl, C １ to C ６ -haloalkyl, cycloalkyl, heterocyclyl, aryl, C １ to C ６ alkylene-aryl, C １ to C ６ alkenylene-aryl, C １ to C ６ alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, -OR Ａ ,-NR Ｂ R Ｃ ,-NR Ｂ C(O)R Ｄ ,-NO ２ ,-C(O)NR Ｂ R Ｃ ,-C(O)R Ｄ ,-C(O)OR Ｄ or -S(O) ｘ R Ｄ wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R ５ ; or Two R １ The groups, together with the atoms to which they are attached, form a 3- to 7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl group, where each cycloalkyl, heterocyclyl, aryl, and heteroaryl group has one or more R groups. ５ It is replaced by an optional choice; Each R ２ These are independently hydrogen or C １ ~C ６ - Alkyl; R ３ C １ ~C ６ - Alkyl, C ２ ~C ６ - Alkenil, C ２ ~C ６ - Alkinyl, 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 ４ is hydrogen, C １ ~C ６ - Alkyl, or C １ ~C ６ - It is a haloalkyl; Each R ５ Independently, C １ ~C ６ - Alkyl, C ２ ~C ６ - Alkenil, C ２ ~C ６ - Alkinyl, C １ ~C ６ - Heteroalkyl, C １ ~C ６ - Haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, oxo, cyano, -OR Ａ , -NR Ｂ R Ｃ , -NR Ｂ C(O)R Ｄ , -NO ２ , -C(O)NR Ｂ R Ｃ , -C(O)R Ｄ , -C(O)OR Ｄ , or -S(O) ｘ R Ｄ Here, each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is one or more R ７ It is replaced by an optional choice; Each R ７ is, independently, C １ to C ６ -alkyl, C １ to C ６ -heteroalkyl, C １ to C ６ -haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or -OR Ａ ; Each R Ａ is, independently, hydrogen, C １ to C ６ alkyl, C １ to C ６ haloalkyl, aryl, heteroaryl, C １ to C ６ alkylene-aryl, C １ to C ６ alkylene-heteroaryl, -C(O)R Ｄ or -S(O) ｘ R Ｄ where; Each R Ｂ and R Ｃ These are, independently, hydrogen and C １ ~C ６ Alkyl, C １ ~C ６ Heteroalkyl, cycloalkyl, heterocyclyl, -OR Ａ Is it R? Ｂ and R Ｃ Along with the atoms to which they are attached, one or more R ９ It forms a 3- to 7-membered heterocyclyl ring which is optionally substituted; Each R Ｄ These are, independently, hydrogen and C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, 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 It is alkylene-heteroaryl; Each R ９ and R １０ Independently, C １ ~C ６ - Alkyl or halo; n is 0, 1, or 2; m is 0, 1, 2, or 3; x is 0, 1, or 2.

2. (iii) A is, 【Chemical 637】 Selected from, in the formula, R １ This is as described in claim 1; or (iv) A, 【Chemical 638】 A compound according to claim 1, selected from the following.

3. (iii) B is, 【Chemistry 641】 Selected from, in the formula, R １ This is as described in claim 1; or (iv) B, 【Chemistry 642】 A compound according to claim 1, selected from the following.

4. L １ and L ２ The compound according to claim 1, wherein each of the is independently absent.

5. The compound of formula (V-a) is the compound of formula (V-c) 【Chemistry 645】 or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, in which A, B, L １ , R ２ , R ３ The compound according to claim 1, wherein m is as described in claim 1.

6. The compound of formula (V-a) 【Chemical 686】 【Chemical 687】 【Chemical Formula 688】 【Chemical 689】 【Chemical 690】 【Chemistry 691】 【Chemistry 692】 【Chemistry 693】 The compound according to claim 1, which is a compound selected from, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

7. A pharmaceutical composition comprising the compound described in claim 1 and a pharmaceutically acceptable additive.

8. The aforementioned compound, (i) Alter the target nucleic acid; (ii) to bind to a target nucleic acid; or (iii) The compound according to claim 1, which stabilizes a target nucleic acid.

9. The aforementioned compound, (i) Increase splicing at splice sites on target nucleic acids by 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; or (ii) The compound according to claim 1, which reduces splicing at splice sites on a target nucleic acid by 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.

10. A composition comprising a compound of formula (V-a) according to claim 1 for use in a method for regulating the splicing of nucleic acids, wherein the method comprises contacting the nucleic acid with the compound of formula (V-a).

11. The aforementioned compound, (i) Increase splicing at splice sites on target nucleic acids by 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; or (ii) The composition according to claim 10, which reduces splicing at splice sites on a target nucleic acid by 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.

12. A composition comprising the compound of formula (V-a) according to claim 1 for use in a method for forming a complex comprising a spliceosome component, a nucleic acid, and the compound of formula (V-a), wherein the method comprises contacting the nucleic acid with the compound of formula (V-a).

13. The composition according to claim 12, wherein the components of the splicesome are supplemented to the nucleic acid in the presence of the compound of formula (V-a).

14. A composition comprising a compound of formula (V-a) according to claim 1 for use in a method for altering the higher-order structure of a nucleic acid, wherein the method comprises contacting the nucleic acid with the compound of formula (V-a).

15. The aforementioned change is (i) forming a curve in the nucleic acid; (ii) Stabilizing the curvature in the nucleic acid; or (iii) The composition according to claim 14, comprising reducing curvature in the nucleic acid.

16. The composition according to claim 14, wherein the nucleic acid includes a splice site.

17. A composition comprising a compound of formula (V-a) as described in claim 1, for treating a disease or disorder in a subject.

18. The aforementioned disease or disorder (i) Proliferative disorders; or (ii) The composition according to claim 17, comprising a nonproliferative disease.

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