TYK2 inhibitors and uses thereof

Abstract

To provide compounds for inhibiting nonreceptor tyrosine-protein kinase 2 (TYK2), also known as Tyrosine kinase 2, and pharmaceutical compositions comprising the compounds.SOLUTION: The present invention provides the following compound, or a pharmaceutically acceptable salt, stereoisomer, or solvate thereof.SELECTED DRAWING: None

Description

Technical Field

[0001] Cross-reference This patent application claims the benefit of U.S. Provisional Patent Application No. 62 / 749,003, filed Oct. 22, 2018; U.S. Provisional Patent Application No. 62 / 756,942, filed Nov. 7, 2018; U.S. Provisional Patent Application No. 62 / 839,459, filed Apr. 26, 2019; U.S. Provisional Patent Application No. 62 / 875,449, filed Jul. 17, 2019; U.S. Provisional Patent Application No. 62 / 893,721, filed Aug. 29, 2019; and U.S. Provisional Patent Application No. 62 / 907,354, filed Sep. 27, 2019, each of which is incorporated herein by reference in its entirety. In this specification, compounds that inhibit non-receptor tyrosine-protein kinase 2 (TYK2), also known as tyrosine kinase 2, methods for preparing such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds are described.

[0002]

Background Art

[0003] TYK2 is a member of the non-receptor tyrosine kinases of the Janus kinase (JAK) family of protein kinases. The mammalian JAK family consists of four members: TYK2, JAK1, JAK2, and JAK3. JAK proteins, including TYK2, are essential for cytokine signaling. TYK2 associates with the cytoplasmic domains of type I and type II cytokine receptors, as well as type I and type III interferon receptors, and cytokine binding ​​​They are activated by their receptors at times. Cytokines involved in TYK2 activation include interferons (e.g., IFN-α, IFN-β, IFN-κ, IFN-δ, IFN-ε, IFN-τ, IFN-ω , and IFN-ζ (also known as limitin)), and interleuk ins (e.g., IL-4, IL-6, IL-10, IL-11, IL-12, IL-13, L-22, IL-23, IL-27, IL-31, oncostatin M, ciliary neurotrophic factor, cardiotrophin 1, cardiotrophin-like cytokine, and LIF). Subsequently, the activated TYK2 then phosphorylates additional signaling proteins such as members of the STAT family including, for example, STAT1, STAT2, STAT4, and STAT6.

[0004] Activation of TYK2 by IL-23 is associated with inflammatory bowel disease (IBD), Crohn's disease, and ulcerative colitis. A genome-level association study of 2,622 psoriatic patients identified an association between disease susceptibility and TYK2. Knockout of TYK2 or tyrphostin inhibition significantly reduces the induced dermatitis of both IL-23 and IL-22.

[0005] TYK2 also plays a role in respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and cystic fibrosis. Goblet cell hyperplasia (GCH) and mucus hypersecretion are mediated by IL-13-induced TYK2 activation, which in turn activates STAT6.

[0006] Reduction of TYK2 activity confers joint protection from collagen antibody-induced arthritis, a model of human rheumatoid arthritis. Mechanistically, decreased Tyk2 activity reduces Th1 / Th17-related cytokine production and production of matrix metalloproteases and other major markers of inflammation.

[0007] TYK2 knockout mice showed complete resistance in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS)), and CD4 T cells did not infiltrate the spinal cord compared to controls. This suggests that TYK2 is essential for the development of pathogenic CD4-mediated diseases in MS. This fact reinforces past studies linking increased TYK2 expression to MS susceptibility. Loss-of-function mutations in TYK2 result in reduced demyelination and increased remyelination of neurons. This also suggests the role of TYK2 inhibitors in the treatment of MS and other demyelinating disorders of the CNS.

[0008] TYK2 is the only signaling messenger common to both IL-12 and IL-23. TYK2 knockout reduced the thickness of the footpad induced by methylated BSA injection in mice and decreased imiquimod-induced psoriatic dermatitis and dextran sulfate sodium-induced or 2,4,6-trinitrobenzene sulfonic acid-induced colitis. In studies on the linkage and association of systemic lupus erythematosus (SLE, an autoimmune disorder) with various type I IFN signaling genes, there was a strong and significant correlation between the disappearance of loss-of-function mutations in TYK2 and a reduced prevalence of SLE in families with affected members. Genome-wide

[0009] studies on individuals in the SLE cohort and non-affected cohorts showed this. ​A highly significant correlation was shown between the TYK2 locus and SLE by the study of the relevance of the model.

[0010] TYK2 has been shown to play an important role in the maintenance of tumor surveillance, and TYK2 knockout mice have been shown to have impaired cytotoxic T cell responses and accelerated tumor development. However, these effects are correlated with the efficient suppression of natural killer (NK) and cytotoxic T lymphocytes, suggesting that TYK2 inhibitors are very suitable for the treatment of autoimmune disorders or transplant rejection. For example, other JAK family members such as JAK3 have similar roles in the immune system, but TYK2 is involved in fewer and more closely related signaling pathways, and accordingly has a reduced off-target effect, so it is proposed as an excellent target. From the study of T cell acute lymphoblastic leukemia (T-ALL), it has been shown that T-ALL is highly dependent on IL-10 by TYK2 via STAT1-mediated signaling, and sustains the survival of cancer cells through upregulation of the anti-apoptosis protein BCL2.

[0011] Knockdown of TYK2, but not other JAK family members, decreased cell proliferation. Specific activating mutations of TYK2 that promote cancer cell survival include mutations in the FERM domain (G36D, S47N, and R425H), JH2 domain (V731I), and kinase domain (E957D and R1027H). However, the TYK2 enzyme characterized by a kinase loss-of-function mutation (M978Y or M978F) in addition to the activating mutation (E957D) failed to transform, indicating that the kinase function of TYK2 is also required for increased cancer cell survival. Therefore, selective inhibition of TYK2, for example, accounts for 70% of cases of adult T cell leukemia

[0012] ​ is proposed as a suitable target for patients with IL-10 and / or BCL2-dependent tumors. TYK2-mediated STAT3 signaling has also been shown to mediate neuronal cell death caused by amyloid-β (Aβ) peptide. Reduction of TYK2 phosphorylation of STAT3 after Aβ administration reduces neuronal cell death. Increased phosphorylation of STAT3 has been observed in the postmortem brains of Alzheimer's patients.

[0013] Inhibition of the JAK-STAT signaling pathway is also involved in hair growth and the recovery of hair loss associated with alopecia areata.

[0014] Therefore, compounds that inhibit the activity of TYK2, particularly compounds having selectivity over JAK2, are beneficial. Such compounds should provide a pharmacological response that treats one or more of the conditions described herein well without the side effects associated with JAK2 inhibition.

[0015] Therefore, there is a need to provide novel inhibitors having more effective and advantageous pharmaceutically relevant properties such as selectivity over other JAK kinases, particularly JAK2.

SUMMARY OF THE INVENTION

[0016] Disclosed herein are compounds of formula (XII), or pharmaceutically acceptable salts, solvates or stereoisomers thereof:

Chemical formula

[0017] Disclosed herein are compounds of formula (XIII) below, or pharmaceutically acceptable salts, stereoisomers or solvates thereof:

Chemical formula

[0018] Also disclosed herein is a pharmaceutical composition comprising a therapeutically effective amount of a compound disclosed herein or a pharmaceutically acceptable salt, stereoisomer or solvate thereof, and a pharmaceutically acceptable excipient.

[0019] Further disclosed herein is a method of inhibiting the TYK2 enzyme in a patient or biological sample, the method comprising contacting the patient or biological sample with a compound disclosed herein or a pharmaceutically acceptable salt, stereoisomer or solvate thereof.

[0020] Furthermore, the present specification also discloses a method for treating a TYK2-mediated disorder, which method comprises administering to a patient in need thereof a compound disclosed herein, or a pharmaceutically acceptable salt, stereoisomer or solvate thereof. In some embodiments, the TYK2-mediated disorder is an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a disorder associated with transplantation. In some embodiments, the disorder is associated with the signaling of type I interferon, IL-10, IL-12, or IL-23. Incorporation by reference

[0021] All published documents, patents, and patent applications mentioned herein are incorporated herein by reference for the specific purposes identified herein.

Mode for Carrying Out the Invention

[0022] Definitions As used in this specification and the appended claims, unless the context clearly dictates otherwise, the singular forms (a, an, and the) also include plural referents. Thus, for example, reference to "a singular agent" includes a plurality of such agents, and reference to "the cell" includes reference to one or more cells (or a plurality of cells) known to those skilled in the art and their equivalents. For physical properties such as molecular weight, or for chemical properties such as chemical formula, when ranges are used herein, all combinations and subcombinations of the ranges and specific embodiments therein are intended to be included. The term "about" when referring to a numerical value or numerical range means that the referenced number or numerical range is an approximation within experimental variation (or within statistical experimental error), and thus in some instances the number or numerical range may vary between 1% and 15% of the recited number or numerical range. The term "comprising" (and related terms such as, for example, "comprises" or "has" or "contains") , In other specific embodiments, for example, it is not intended to exclude embodiments such as any composition of matter, composition, method, or process described herein from consisting of the recited properties or consisting essentially of the recited properties.

[0023] As used in this specification and the appended claims, unless the contrary is expressly stated, the following terms have the meanings set forth below.

[0024] "Aliphatic chain" refers to a straight-chain chemical moiety consisting of only carbon and hydrogen. In some embodiments, the aliphatic chain is saturated. In some embodiments, the aliphatic chain is unsaturated. In some embodiments, the unsaturated aliphatic chain contains one unsaturation. In some embodiments , the unsaturated aliphatic chain contains two or more unsaturations. In some embodiments, the unsaturated aliphatic chain contains two unsaturations. In some embodiments, the unsaturated aliphatic chain contains one double bond. In some embodiments, the unsaturated aliphatic chain contains two double bonds.

[0025] "Alkyl" refers to an optionally substituted straight-chain or optionally substituted branched-chain saturated hydrocarbon monoradical having from 1 to about 10 carbon atoms, or from 1 to 6 carbon atoms. Examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl -3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, tert- pentyl, etc. As used herein, the term "alkyl" refers to any alkyl group that is longer than 1,000 carbon atoms, such as aryl, amyl, and hexyl, as well as longer chain alkyl groups such as heptyl, aryl, and the like. 1- The numerical ranges for "C6 alkyl" etc. The alkyl group may have 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, and this definition extends to the range of values ​​specified. In some embodiments, alkyl is a C 1- C 10 Alkyl, C 1- C9 alkyl, C 1- C8 alkyl, C 1- C7 alkyl, C 1- C6 alkyl, C 1- C5 alkyl, C 1- C4 alkyl, C 1- C3 alkyl, C 1- C2 alkyl, or C1 alkyl. Unless otherwise specifically stated herein, alkyl groups are optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, alkyl is optionally substituted with oxo, halogen, -CN, -CF3, OH, -OMe, NH2, or -NO2. In some embodiments, alkyl is optionally substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, alkyl is optionally substituted with halogen.

[0026] "Alkenyl" means an alkyl group having one or more carbon-carbon double bonds or having from 2 to about 10 carbon atoms. Refers to an optionally substituted linear or optionally substituted branched hydrocarbon monoradical having a carbon atom, preferably having 2 to about 6 carbon atoms. It should be understood that this period may be in either the cis or trans conformation with respect to the double bond, and both isomers are included. Examples include, but are not limited to, ethenyl (-CH=CH2), 1-propenyl (-CH2CH=CH2), isopropenyl [-C(CH3)=CH2], butenyl, 1,3-butadienyl, and the like. When displayed in this specification, for example, a numerical range such as "C 2- C6 alkenyl" means that the alkenyl group can consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, and this definition also applies when the term " alkenyl" appears without a specified numerical range. In some embodiments, the alkenyl is C C 2- C 10 alkenyl, C 2- C9 alkenyl, C 2- C8 alkenyl, C 2- C7 alkenyl, C 2- C6 alkenyl, C 2- C5 alkenyl, C 2- C4 alkenyl, C 2- C3 alkenyl, or C2 alkenyl is. Unless specifically stated otherwise herein, the alkenyl group is optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, the alkenyl is optionally substituted with oxo, halogen, -CN, -CF3, OH, -OMe, NH2, or -NO2. In some embodiments, the alkenyl is optionally substituted with oxo, halogen, -CN, -CF3, OH, or -OMe. In some embodiments the alkenyl is optionally substituted with halogen.

[0027] "Alkynyl" refers to an optionally substituted straight-chain or optionally substituted branched-chain hydrocarbon monoradical having one or more carbon-carbon triple bonds, or having from 2 to about 10 carbon atoms, more preferably having from 2 to about 6 carbon atoms. Examples include, but are not limited to, ethynyl, 2-propynyl, 2-butynyl, 1,3-butadiynyl, and the like. When displayed in this specification, for example, a numerical range such as "C 2- C6 alkynyl" means that the alkynyl group can consist of 2, 3, 4, 5, or 6 carbon atoms, and this definition also applies when the term "alkynyl" appears without a specified numerical range. In some embodiments, alkynyl is C C alkynyl, C C9 alkynyl, C 2- C 10 C8 alkynyl, C 2- C9 alkynyl, C 2- C8 alkynyl, C 2- C7 alkynyl, C 2- C6 alkynyl, C 2- C5 alkynyl, C 2- C4 alkynyl, C 2- C3 alkynyl, or C2 alkynyl. Unless specifically stated otherwise herein, the alkynyl group is optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, alkynyl is optionally substituted with oxo, halogen, -CN, -CF3, OH, -OMe, NH2, or -NO2. In some embodiments, alkynyl is optionally substituted with oxo, halogen, -CN, -CF3, OH, or -OMe. In some embodiments are, alkynyl is optionally substituted with halogen. "Alkylene" refers to a straight-chain or branched-chain divalent hydrocarbon chain. In this specification

[0028] ​ Unless specifically stated otherwise, the alkylene group can be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkylene is optionally substituted with oxo, halogen, -CN, -CF3, OH, -OMe, NH2, or -NO2. In some embodiments, the alkylene is optionally substituted with oxo, halogen,, -CN, -CF3, OH or -OMe. In some embodiments, the alkylene is , optionally substituted with halogen.

[0029] "Alkoxy" refers to a radical of the formula -OR a , wherein R a is a defined alkyl radical . Unless specifically stated otherwise herein, the alkoxy group can be optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkoxy is optionally substituted with oxo, halogen, -CN, -CF3, OH, -OMe, NH2, or -NO2. In some embodiments, the alkoxy is optionally substituted with oxo, halogen, CN, -CF3, OH or -OMe. In some embodiments, the alkoxy is optionally substituted with halogen.

[0030] "Aminoalkyl" refers to an alkyl radical as defined above substituted with one or more amines. In some embodiments, the alkyl is substituted with 1 amine. In some embodiments, the alkyl is substituted with 1, 2, or 3 amines. Examples of hydroxyalkyl include, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the hydroxyalkyl is aminomethyl.

[0031] "Aryl" refers to a radical derived from a hydrocarbon ring system containing hydrogen, 6 to 30 carbon atoms, and at least one aromatic ring. The aryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system and may include fused (when fused to a cycloalkyl or heterocycloalkyl ring, the aryl is bonded through an aromatic ring atom) or bridged ring systems. In some embodiments, an aryl is a 6- to 10-membered In some embodiments, the aryl is a 6-membered aryl. Radicals include, but are not limited to, anthrylene, naphthylene, phenanthrylene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, as-indacene, Aryl radicals derived from the hydrocarbon ring systems of acene, s-indacene, indane, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and triphenylene. In some embodiments, the aryl is phenyl. Unless otherwise specifically stated herein, the aryl can be optionally substituted with, for example, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the aryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF3, OH, -OMe, NH2, or -NO2. In some embodiments, the aryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF3, OH, or -OMe. In some embodiments, the aryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF3, OH, or -OMe. In embodiments, the aryl is optionally substituted with halogen.

[0032] "Cycloalkyl" refers to a stable, partially or fully saturated, monocyclic or polycyclic carbocyclic ring, which may be fused (when fused with an aryl or heteroaryl ring, Cycloalkyl includes ring systems bonded via a non-aromatic ring atom or bridged ring systems. is possible. Representative cycloalkyls include, but are not limited to, cycloalkyls having 3 to 15 carbon atoms (C 3- C 15 cycloalkyl), cycloalkyls having 3 to 10 carbon atoms (C 3- C 10 cycloalkyl), cycloalkyls having 3 to 8 carbon atoms (C 3- C8 cycloalkyl), cycloalkyls having 3 to 6 carbon atoms (C 3- C6 cycloalkyl), cycloalkyls having 3 to 5 carbon atoms (C 3- C5 cycloalkyl), or cycloalkyls having 3 to 4 carbon atoms (C 3- C4 cycloalkyl). In some embodiments, the cycloalkyl is a 3- to 6-membered cycloalkyl. In some embodiments, the cycloalkyl is a 5- to 6-membered cycloalkyl. Examples of monocyclic cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of polycyclic cycloalkyls or carbocycles include adamantyl, norbornyl, decalinyl, bicyclo[3.3.0]octane, bicyclo[4.3.0]nonane, cis-decalin, trans-decalin, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, and bicyclo[3.3.2]decane, and 7,7-dimethyl-bicyclo[2.2.1]hep tanil. Examples of partially saturated cycloalkyls include cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless specifically stated otherwise herein, the cycloalkyl is optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the cycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, OH, -OMe, NH2, or -NO2. In some embodiments, the cycloalkyl is oxo, halogen, methyl, ethyl, -CN, -CF3, OH, or -OMe, and is optionally substituted. In some embodiments, the cycloalkyl is optionally substituted with halogen.

[0033] "Deuteroalkyl" refers to an alkyl radical as defined above, substituted by one or more deuterium atoms. In some embodiments, the alkyl is substituted with 1 deuterium atom. In some embodiments, the alkyl is substituted with 1, 2 or 3 deutero atoms. In some embodiments, the alkyl is substituted with 1, 2, 3, 4, 5 or 6 deuterium atoms. Examples of deuteroalkyl include CD3, CH2D, CHD2, CH2CD3, CD2CD3, CHDCD3, CH2CH2D, or CH2CHD2. In some embodiments, the deuteroalkyl is CD3.

[0034] "Haloalkyl" refers to an alkyl radical as defined above, substituted by one or more halogen atoms. In some embodiments, the alkyl is substituted with 1, 2 or 3 halo gen atoms. In some embodiments, the alkyl is substituted with 1, 2, 3, 4, 5 or 6 halogens. Examples of haloalkyl include trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl, etc. are included. In some embodiments, the haloalkyl is trifluoromethyl.

[0035] "Halo" or "halogen" refers to bromo, chloro, fluoro, or iodo. In some embodiments, the halogen is fluoro or chloro. In some embodiments, the halogen is fluoro.

[0036] "Heteroalkyl" refers to an alkyl group in which one or more of the skeletal atoms of the alkyl are selected from atoms other than carbon, such as oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, or combinations thereof. The heteroalkyl is attached to the remainder of the molecule by a carbon atom of the heteroalkyl. In one embodiment, the heteroalkyl is a C1-C6 heteroalkyl, in which case the heteroalkyl consists of 1 to 6 carbon atoms and one or more atoms other than carbon such as oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur or combinations thereof, and in this case the heteroalkyl is attached to the remainder of the molecule by a carbon atom of the heteroalkyl. Examples of such heteroalkyls are, for example, -CH2OCH3, -CH2CH2OCH3, -CH2CH2OCH2CH2OCH3, or -CH(CH3)OCH3. Unless specifically stated otherwise herein, heteroalkyl is optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, OH, -OMe, NH2, or -NO2. In some embodiments, heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, OH, or -OMe. In some embodiments, heteroalkyl is optionally substituted with halogen. "Hydroxyalkyl" refers to an alkyl radical as defined above substituted by one or more hydroxyls. In some embodiments, the alkyl is substituted with 1 hydroxyl. In some embodiments, the alkyl is substituted with 1, 2, or 3 hydroxyls.

[0037] It is replaced. Examples of the hydroxyalkyl include hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, or hydroxypentyl. In some embodiments, the hydroxyalkyl is hydroxymethyl.

[0038] "Heterocycloalkyl" means a stable 3- to 24-membered partially saturated or fully saturated ring radical containing 2 to 23 carbon atoms and 1 to 8 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus, and sulfur. In some embodiments, the heterocycloalkyl contains 1 or 2 heteroatoms selected from nitrogen and oxygen. Unless specifically stated otherwise herein, the heterocycloalkyl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include a fused (when fused to an aryl ring or a heteroaryl ring, the heterocycloalkyl is attached via a non-aromatic ring atom) ring system, or a bridged ring system. And the nitrogen atom, carbon atom, or sulfur atom in the heterocycloalkyl radical may optionally be oxidized, and the nitrogen atom may optionally be quaternized. Representative heterocycloalkyls include, but are not limited to, those having 2 to 15 carbon atoms (C C heterocycloalkyl), 2 to 10 carbon atoms (C C 2- C 15 heterocycloalkyl), 2 to 8 carbon atoms (C 2- C 10 hetero cycloalkyl), 2 to 6 carbon atoms (C2-C6 heterocycloalkyl), 2 to 5 carbon atoms (C2-C5 heterocycloalkyl), or 2 to 4 carbon atoms (C2-C4 heterocycloalkyl). In some embodiments, the heterocycloalkyl is a 3- to 6-membered heterocycloalkyl. In some embodiments, the cycloalkyl is a 5- to 6-membered heterocycloalkyl. Examples of such heterocycloalkyl radicals include, but are not limited to, aziridine 2- C8 heterocycloalkyl), 2 to 6 carbon atoms (C2-C6 heterocycloalkyl), 2 to 5 carbon atoms (C2-C5 heterocycloalkyl), or 2 to 4 carbon atoms (C2-C4 heterocycloalkyl). In some embodiments, the heterocycloalkyl is a 3- to 6-membered heterocycloalkyl. In some embodiments, the cycloalkyl is a 5- to 6-membered heterocycloalkyl. Examples of such heterocycloalkyl radicals include, but are not limited to, aziridine dithienyl, azetidinyl, dioxolanyl, thienyl[1, 3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperyl, Razinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, 1,3-dihydroisobenzofuran-1-yl, 3-oxo-1,3-dihydroisobenzofuran-1-yl, methyl-2-oxo-1,3-dioxol-4-yl, and 2-oxo-1,3-dioxo The term heterocycloalkyl includes, but is not limited to, monosaccharides. Also included are carbohydrates of all ring types, including saccharides, disaccharides, and oligosaccharides. When referring to the number of carbon atoms in a heterocycloalkyl, the number of carbon atoms in the heterocycloalkyl refers to the total number of atoms (including heteroatoms) that make up the heterocycloalkyl (i.e., the It is understood that the total number of skeletal atoms of the heterocycloalkyl ring is not the same as the total number of skeletal atoms of the heterocycloalkyl ring. Unless specifically stated otherwise in, heterocycloalkyl is optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, heterocycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, OH, -OMe, NH2, or -NO2. In some embodiments, heterocycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, OH, or -OMe. In some embodiments, In the heterocycloalkyl, the heterocycloalkyl is optionally substituted with halogen.

[0039] "Heteroalkyl" refers to an alkyl group in which one or more skeletal atoms of the alkyl are selected from atoms other than carbon, such as oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, or combinations thereof. The heteroalkyl is attached to the remainder of the molecule by a carbon atom of the heteroalkyl. In one embodiment, the heteroalkyl is C C6 heteroalkyl. Unless specifically stated otherwise herein, the heteroalkyl is optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, OH, -OMe, NH2, or -NO2. In some embodiments, the heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, OH, or -OMe. In some embodiments 1- C6 heteroalkyl is optionally substituted with halogen.

[0040] "Heteroaryl" refers to a 5- to 14-membered ring system radical that contains a hydrogen atom, 1 to 13 carbon atoms, 1 to 6 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus, and sulfur, and at least one aromatic ring. The heteroaryl radical may be monocyclic, bicyclic, tricyclic, or tetracyclic ring systems, and the ring systems may include fused (when fused with a cycloalkyl ring or a heterocycloalkyl ring, the heteroaryl is attached via an aromatic ring atom) ring systems, or bridged ring systems. And the nitrogen atoms, carbon atoms, or sulfur atoms in the heteroaryl radical may be optionally oxidized, and the nitrogen atoms may be optionally quaternized. In some embodiments, the heteroaryl is a 5- to 10-membered he teroaryl. teroaryl. cyclic or heterocyclic ring, the heteroaryl is attached via an aromatic ring atom), or bridged ring systems may be included. And the nitrogen atoms, carbon atoms, or sulfur atoms in the heteroaryl radical may be optionally oxidized, and the nitrogen atoms may be optionally quaternized. In some embodiments, the heteroaryl is a 5- to 10-membered he teroaryl. It is a heteroaryl. In some embodiments, the heteroaryl is a 5- to 6-membered heteroaryl. Examples include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, isothiazolyl, imidazolyl, indazolyl , indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopyridazinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e., thienyl). As used herein Unless specifically stated otherwise, heteroaryl is optionally substituted with, for example, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl and the like. In some embodiments, heteroaryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF3, OH, -OMe, NH2, or -NO2. In some embodiments, heteroaryl is optionally substituted with halogen, methyl, ethyl, -CN, -CF3, OH, or -OMe. In some embodiments, heteroaryl is optionally substituted with halogen.

[0041] As used herein, the terms “treat,” “prevent,” “ameliorate,” and “inhibit,” and words derived therefrom, do not necessarily mean 100% or complete treatment, prevention, amelioration, or inhibition. Rather, there are varying degrees of treatment, prevention, amelioration, and inhibition thereof, and one of ordinary skill in the art would recognize a potential benefit or therapeutic effect as such. In this regard, the methods of the present disclosure can provide any amount of any level of treatment, prevention, amelioration, or inhibition in a mammal. For example, a disorder, including its symptoms or conditions, can be reduced by about 100%, about 90%, about 80%, about 70%, about 60%, about 50%, about 40%, about 30%, about 20%, or about 10%. Further, the treatment, prevention, amelioration, or inhibition provided by the methods disclosed herein can include the treatment, prevention, amelioration, or inhibition of one or more conditions or symptoms of a disorder such as cancer or an inflammatory disease. Also, for the purposes of this specification, “treat,” “prevent,” “ameliorate,” or “inhibit” encompasses delaying the onset of a disorder, or delaying the occurrence of its symptoms or conditions.

[0042] As used herein, the terms "effective amount" or "therapeutically effective amount" refer to a sufficient amount of a compound disclosed herein to be administered to alleviate to some extent one or more of the symptoms, or conditions, of a disease being treated, such as cancer or an inflammatory disease. In some embodiments, the result is a decrease and / or alleviation of the signs, symptoms or causes of the disease, or any other desirable change in a biological system. For example, an "effective amount" for therapeutic use is the amount of a composition comprising a compound disclosed herein required to effect a clinically significant decrease in a disease symptom. In some embodiments, an appropriate "effective" amount in any individual case is determined using techniques such as dose escalation studies.

[0043] As used herein, the term "TYK2-mediated" disorder, disease, and / or condition means any disease or other adverse condition in which TYK2 or a variant thereof is known to play a role. Thus, another embodiment relates to treating or reducing the severity of one or more diseases in which TYK2 or a variant thereof is known to play a role. Such TYK2-mediated disorders include, but are not limited to, autoimmune disorders, inflammatory disorders, proliferative disorders, endocrine disorders, neurological disorders, and disorders related to transplantation. Compound

[0044] Disclosed herein are compounds useful for the treatment of TYK2-mediated disorders. In some embodiments the TYK2-mediated disorder is an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a disorder related to transplantation.

[0045] Disclosed herein are compounds of formula (I) below, or pharmaceutically acceptable salts, solvates or stereoisomers thereof:

Chemical formula

[0046] In some embodiments of the compound of formula (I), L is a bond. In some embodiments of the compound of formula (I), L is -C(=O)-.

[0047] In some embodiments of the compound of formula (I), ring A is heterocycloalkyl or heteroaryl; each optionally substituted with one or more R A . In some embodiments of the compound of formula (I), ring A is a 5-membered heterocycloalkyl or a 5-membered heteroaryl; each optionally substituted with one or more R ; Ais optionally substituted. In some embodiments of the compound of formula (I), ring A is one or more R A is a heteroaryl optionally substituted with

[0048] In some embodiments of the compound of formula (I), each R A is independently deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (I), each R A is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (I), each R A is independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (I), each R A is independently C1-C6 alkyl.

[0049] In some embodiments of the compound of formula (I), R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compound of formula (I), R 4 is hydrogen or -OR b . In some embodiments of the compound of formula (I), R4 is -OR b and exists. In some embodiments of the compound of formula (I), R 4 is hydrogen.

[0050] In some embodiments of the compound of formula (I), the compound is a compound of the following formula (Ia):

Chemical formula

[0051] In some embodiments of the compound of formula (I), the compound is a compound of the following formula (Ib):

Chemical formula

[0052] In some embodiments of the compound of formula (I), (Ia) or (Ib), R 3 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (I), (Ia) or (Ib), R 3 is hydrogen.

[0053] In some embodiments of the compound of formula (I), (Ia) or (Ib), Z is a bond or -CH2- and. In some embodiments of the compound of formula (I), (Ia) or (Ib), Z is -CH2- is. In some embodiments of the compound of formula (I), (Ia) or (Ib), Z is a bond.

[0054] In some embodiments of the compound of formula (I), (Ia) or (Ib), R 1 and R 2 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In the formula (I), (Ia) or (Ib), in some embodiments of the compound, R 1 and R 2 are independently hydrogen a moiety of a compound of formula (I), (Ia) or (Ib) which is hydrogen, or C1-C6 deuterated alkyl In embodiments of 1 , R is hydrogen. In embodiments of a moiety of a compound of formula (I), (Ia) or (Ib) , R 2 is C1-C6 alkyl, or C1-C6 deuterated alkyl. In embodiments of a moiety of a compound of formula (I), (Ia) or (Ib), R 2 is C1-C6 deuterated alkyl.

[0055] In embodiments of a moiety of a compound of formula (I), (Ia) or (Ib), R 5 is halogen, -CN, -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OR , -NR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1-C6 alkyl, or C 1- is optionally substituted with C6 haloalkyl.

[0056] In some embodiments of the compounds of formula (I), (Ia) or (Ib), R 5 is -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, or C 1- is optionally substituted with C6 haloalkyl .

[0057] In some embodiments of the compounds of formula (I), (Ia) or (Ib), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , or one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b, -C(=O)NR c R d 、C 1- C6 alkyl, or C 1- aryl optionally substituted with C6 haloalkyl.

[0058] In some embodiments of the compounds of formula (I), (Ia) or (Ib), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d ,C 1- C6 alkyl, or C 1- aryl optionally substituted with C6 haloalkyl. In some embodiments of the compounds of formula (I), (Ia) or (Ib), R 5 is -NR 8 C(=O)R 7 In some embodiments of the compounds of formula (I), (Ia) or (Ib), R 5 is , one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or aryl optionally substituted with C1-C6 haloalkyl.

[0059] In some embodiments of the compounds of formula (I), (Ia) or (Ib), R7 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein alkyl, cycloalkyl, each of heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (I), (Ia) or (Ib), R 7 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (I), (Ia) or (Ib), R 7 is cycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (I), (Ia) or (Ib), R 7 is unsubstituted cycloalkyl.

[0060] In some embodiments of the compounds of formula (I), (Ia) or (Ib), R 8is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (I), (Ia) or (Ib), R 8 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl.

[0061] In some embodiments of the compounds of formula (I), (Ia) or (Ib), R 9 and R 10 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (I), (Ia) or (Ib), R 9 and R 10 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl is a kill; in this case, each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl.

[0062] In this specification, compounds of the following formula (II) or (II'), or pharmaceutically acceptable possible salts, stereoisomers or solvates are disclosed:

Chemical formula

[0063] In some embodiments of the compound of formula (II) or (II'), L is a bond. In some embodiments of the compound of formula (II) or (II'), L is -C(=O)-.

[0064] In some embodiments of the compound of formula (II) or (II'), ring A is heterocycloalkyl or heteroaryl; each optionally substituted with one or more R A In some embodiments of the compound of formula (II) or (II'), ring A is 5-membered heterocycloalkyl or 5-membered heteroaryl; each optionally substituted with one or more R A In some embodiments of the compound of formula (II) or (II') ring A of the compound is heteroaryl optionally substituted with one or more R A is.​

[0065] In some embodiments of the compound of formula (II) or (II'), each R A is independently deuterium, halo gen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- 6 alkyl, C 1- 6 haloalkyl, or C 1- 6 deuterated alkyl. In some embodiments of the compound of formula (II) or (II'), each R A is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (II) or (II') , each R A is independently halogen or C1-C6 alkyl . In some embodiments of the compound of formula (II) or (II'), each R A is independently C1-C6 alkyl.

[0066] In some embodiments of the compound of formula (II) or (II'), R 4 is hydrogen, deuterium, halo gen,, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (II) or (II'), R 4 is hydrogen or -ORb is. In some embodiments of the compound of formula (II) or (II'), R 4 is -OR b is. In some embodiments of the compound of formula (II) or (II') in, R 4 is hydrogen.

[0067] In some embodiments of the compound of formula (II) or (II'), X is -CH-. In some embodiments of the compound of formula (II) or (II'), X is -N-.

[0068] In some embodiments of the compound of formula (II) or formula (II'), the compound is a compound of the following formula (IIa) or formula (II'a).

Chemical formula

[0069] In some embodiments of the compound of formula (II) or formula (II'), the compound is a compound of the following formula (IIb) or formula (II'b).

Chemical formula

[0070] In some embodiments of the compound of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b) in, R 3 is hydrogen or C1-C6 alkyl. In formula (II), (II'), (IIa), (II'a), (IIb), or (II'b) in some embodiments of the compound, R 3 is hydrogen .

[0071] In some embodiments of the compound of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b) in, R 1 and R 2is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b), R 1 and R 2 are independently hydrogen, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b), R 1 is hydrogen. In some embodiments of the compounds of formula (II), (II'), (IIa) , (II'a), (IIb), or (II'b), R 2 is C1-C6 alkyl, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b), R 2 is C1-C6 deuterated alkyl.

[0072] In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b), R 5 is halogen, -CN, -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 ,, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, he is a terocycloalkyl, aryl or heteroaryl; in which case each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently, one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d ,C 1- C6 alkyl, or C 1- is optionally substituted with C6 haloalkyl.

[0073] In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b), R is, -OR 5 , -NR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; in which case each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , is optionally substituted with C1-C6 alkyl, or C1-C6 haloalkyl.

[0074] In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , or one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , and is aryl optionally substituted with C1-C6 alkyl or C1-C6 haloalkyl.

[0075] In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 al kyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b), R 5 is -NR 8 C(=O)R 7 and Yes. One of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b) In some embodiments, R 5 is one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d and is aryl optionally substituted with C1-C6 alkyl or C1-C6 haloalkyl.

[0076] In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b) R 7 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b) R is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated 7 alkyl ​​is alkyl or cycloalkyl; in which case each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or in some embodiments of the compounds of (II'b), R 7 is cycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b), R 7 is unsubstituted cycloalkyl.

[0077] In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b), R 8 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; in which case each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b) R 8 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; in which case alkyl, cyclo Each of lower alkyl and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl.

[0078] In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b), R 9 and R 10 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb) , or (II'b), R 9 and R 10 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl.

[0079] In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b), R 11 is deuterium, halogen, -CN, -OR b, -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d 、C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- is C6 deuterated alkyl . In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b), R 11 is deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or in some embodiments of the compounds of (II'b), R 11 is halogen. In some embodiments of the compounds of formula (II), (II'), (IIa), (II'a), (IIb), or (II'b), R 11 is hydrogen.

[0080] Disclosed herein are compounds of the following formula (III), or pharmaceutically acceptable salts, stereoisomers or solvates thereof: : [Chemical formula] Wherein: Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, provided that [Chemical formula] is not; each R B is independently hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR cR d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b ,C 1- C6 alkyl, C alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; or two Rs on the same carbon B form oxo together; or two Rs on adjacent atoms B form cycloalkyl, heterocycloalkyl, aryl, or heteroaryl together; each being optionally substituted with one or more deuterium, oxo, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, C 1- C6 deuterium ated alkyl, or C 1- C6 haloalkyl; n is from 0 to 4; each Y is independently C or N; R 3 is hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl; ; R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b ,C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoal kyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; or R 3 and R 4 together optionally form a substituted ring; L is a bond or -C(=O)-; Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ; each of them has one or more RA is optionally replaced with; each R A is independently deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, or C 1-Optionally substituted with C6 haloalkyl; or two Rs on the same carbon A together form an oxo; X is -CR x - or -N-; R X is hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b , -NR a C(=O)R b , -NR b ,C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoal kyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; R 5 is halogen, -CN, -OR 8 , -SR 8 , -S(=O)R 7 , -S(=O)2R 7 , -NO2, -NR 9 R 10 , -NHS(=O)2R 7, -S(=O)2NR 9 R 10 , -C(=O)R 7 , -OC(=O)R 7 , -C(=O)OR 8 , -OC(=O)OR 8 , -C(=O)NR 9 R 10 , -OC(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d ,, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; or R X and R 5 together form a ring D optionally substituted with one or more R D ; ring D is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ; each RD is independently hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b 、C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d ,、C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; or two Rs on the same carbon together form an oxo; D and R 7 is C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; where in each case alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are each independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- C6 haloal kyl; each R 8 is independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; where in each case alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are each independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe,, C 1- C6 alkyl, or C 1- C6 haloalkyl; R 9 and R 10 are independently hydrogen, C1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; or R 9 and R 10 together with the nitrogen atom to which they are attached form one or more oxo, deuterium element, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- heterocycloalkyl optionally substituted with C6 haloalkyl; each R a is independently C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cyclo alkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; each R b is independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or or C 1- optionally substituted with C6 haloalkyl; each R c and R d is independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated al kyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or 1- optionally substituted with C6 haloalkyl; or R cand R d together with the nitrogen atom to which they are attached, one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- forms a heterocycloalkyl optionally substituted with C6 haloalkyl.

[0081] In some embodiments of the compound of formula (III), L is a bond. In one embodiment of the compound of formula (III), L is -C(=O)-.

[0082] In some embodiments of the compound of formula (III), ring A is heterocycloalkyl or heteroaryl; each optionally substituted with one or more R A . In some embodiments of the compound of formula (III), ring A is a 5-membered heterocycloalkyl or a 5-membered heteroaryl; each optionally substituted with one or more R . In some embodiments of the compound of formula (III), ring A is a heteroaryl optionally substituted with one or more R A . A

[0083] In some embodiments of the compound of formula (III), each R A is independently deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compound of formula (III), each R Ais independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (III), each R A is independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (III), each R A is independently C1-C6 alkyl.

[0084] In some embodiments of the compound of formula (III), R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compound of formula (III), R 4 is hydrogen or -OR b . In some embodiments of the compound of formula (III), R 4 is -OR b . In some embodiments of the compound of formula (III), R 4 is hydrogen.

[0085] In some embodiments of the compound of formula (III), X is -CH-. In one embodiment of the compound of formula (III), X is -N-.

[0086] In some embodiments of the compound of formula (III), the compound is a compound of formula (IIIa) below.

Chemical formula

[0087] In some embodiments of the compound of formula (III), the compound is a compound of formula (IIIb) below.

Chemical formula

[0088] In some embodiments of the compounds of formula (III), (IIIa) or (IIIb), R 3 is hydrogen or is C1-C6 alkyl. In some embodiments of the compounds of formula (III), (IIIa) or (IIIb), R 3 is hydrogen.

[0089] In some embodiments of the compounds of formula (III), (IIIa) or (IIIb), R 5 is halogen , -CN, -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 ,, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b, -C(=O)NR c R d , C 1- C6 alkyl, or C 1- is optionally substituted with C6 haloalkyl.

[0090] In some embodiments of the compounds of formula (III), (IIIa), or (IIIb), R 5 is -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl ; wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or is optionally substituted with C1-C6 haloalkyl.

[0091] In some embodiments of the compounds of formula (III), (IIIa) or (IIIb), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , or one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)Ra , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or aryl optionally substituted with C1-C6 haloalkyl is.

[0092] In some embodiments of the compounds of formula (III), (IIIa), or (IIIb), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , cycloalkyl, heterocycloalkyl, aryl or hetero aryl; wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or optionally substituted with C1-C6 haloalkyl is. In some embodiments of the compounds of formula (III), (IIIa) or (IIIb), R 5 is -NR 8 C(=O)R 7 is. In some embodiments of the compounds of formula (III), (IIIa) or (IIIb), R 5 is one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or aryl optionally substituted with C1-C6 haloalkyl.

[0093] In some embodiments of the compound of formula (III), (IIIa) or (IIIb), R 7 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compound of formula (III), (IIIa) or (IIIb), R 7 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compound of formula (III), (IIIa) or (IIIb), R 7 is cycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compound of formula (III), (IIIa) or (IIIb), R 7 is unsubstituted cycloalkyl.

[0094] In some embodiments of the compound of formula (III), (IIIa) or (IIIb), R 8is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (III), (IIIa) or (IIIb), R 8 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl.

[0095] In some embodiments of the compounds of formula (III), (IIIa) or (IIIb), R 9 and R 10 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cyclo alkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (III), (IIIa) or (IIIb), R 9 and R 10 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or is cycloalkyl; in this case, each of alkyl, cycloalkyl, and heterocycloalkyl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl optionally substituted.

[0096] In some embodiments of the compounds of formula (III), (IIIa), or (IIIb), ring B is heterocycloalkyl or heteroaryl.

[0097] In some embodiments of the compounds of formula (III), (IIIa) or (IIIb),

Chemical formula

[0098] In some embodiments of the compounds of formula (III), (IIIa), or (IIIb), each R B is independently hydrogen, deuterium, halogen, -CN, -OR , -NR b R c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl; or two Rs on the same carbon together form oxo. In some B embodiments of the compounds of formula (III), (IIIa), or (IIIb), each R is independently hydrogen, deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl; or two Rs on the same carbon together B form B oxo. ​

[0099] In some embodiments of the compounds of formula (III), (IIIa), or (IIIb), two R B s together form cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each is independently optionally substituted with one or more deuterium, oxo, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, C 1- C6 deuterated alkyl, or C 1- C6 haloalkyl. In some embodiments of the compounds of formula (III), (IIIa), or (IIIb), two R B s together form heterocycloalkyl or heteroaryl; each is independently optionally substituted with one or more deuterium, oxo, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, C 1- C6 deuterated alkyl, or C 1- C6 haloalkyl;

[0100] In some embodiments of the compounds of formula (III), (IIIa), or (IIIb), n is 0. In some embodiments of the compounds of formula (III), (IIIa), or (IIIb), n is 1. In some embodiments of the compounds of formula (III), (IIIa), or (IIIb), n is 2. In some embodiments of the compounds of formula (III), (IIIa), or (IIIb), n is 0 - 2. In formula In some embodiments of the compound of (III), (IIIa) or (IIIb), n is 0 or 1. In some embodiments of the compound of formula (III), (IIIa) or (IIIb), n is 1 or 2. In some embodiments of the compound of formula (III), (IIIa) or (IIIb), n is 1 to 3.

[0101] In some embodiments of the compound of formula (III), (IIIa) or (IIIb), n' is 0. In some embodiments of the compound of formula (III), (IIIa) or (IIIb), n' is 1. In some embodiments of the compound of formula (III), (IIIa) or (IIIb), n' is 2. In some embodiments of the compound of formula (III), (IIIa) or (IIIb), n' is from 0 to 2 is. In some embodiments of the compound of formula (III), (IIIa) or (IIIb), n' is 0 or 1. In some embodiments of the compound of formula (III), (IIIa) or (IIIb), n' is 1 or 2.

[0102] Disclosed herein is a compound of the following formula (IV), or a pharmaceutically acceptable salt, stereoisomer or solvate thereof:

Chemical formula

[0103] In some embodiments of the compound of formula (IV), L is a bond. In some Embodiments of the compound of formula (IV), L is -C(=O)-.

[0104] In some embodiments of the compound of formula (IV), ring A is heterocycloalkyl or hetero Aryl; each with one or more R Ais optionally substituted. In some embodiments of the compound of formula (IV), ring A is a 5-membered heterocycloalkyl or a 5-membered heteroaryl; each one or more R A is optionally substituted. In some embodiments of the compound of formula (IV), ring A is a one or more R A optionally substituted heteroaryl.

[0105] In some embodiments of the compound of formula (IV), each R A is independently deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compound of formula (IV), each R A is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (IV), each R A is independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (IV), each R A is independently C1-C6 alkyl.

[0106] In some embodiments of the compound of formula (IV), R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NRc R d 、 C 1- C6 alkyl, C 1- C6 halo alkyl, or C 1- C6 deuterated alkyl. Some embodiments of the compound of formula (IV) in, R 4 is hydrogen or -OR b . Some embodiments of the compound of formula (IV) in, R 4 is -OR b . Some embodiments of the compound of formula (IV) in, R 4 is hydrogen.

[0107] In some embodiments of the compound of formula (IV), X is -CH-. Some of the compounds of formula (IV) in the embodiment, X is -N-.

[0108] In some embodiments of the compound of formula (IV), the compound is a compound of the following formula (IVa) :

Chemical formula

[0109] In some embodiments of the compound of formula (IV), the compound is a compound of the following formula (IVb) :

Chemical formula

[0110] In some embodiments of the compound of formula (IV), (IVa) or (IVb), R 12 is -C(=O)NR 1 R 2 .

[0111] In some embodiments of the compound of formula (IV), (IVa) or (IVb), R 1 and R 2is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R 1 and R 2 are independently hydrogen, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R 1 is hydrogen. In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R 2 is C1-C6 alkyl, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R 2 is C1-C6 deuterated al kyl.

[0112] In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R 12 is -L 1 -R 13 wherein.

[0113] In some embodiments of the compounds of formula (IV), (IVa) or (IVb), L 1 is -NH-. In some embodiments of the compounds of formula (IV), (IVa) or (IVb), L 1 is -O- or -NH- wherein.

[0114] In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R 13 is C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl.

[0115] In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R 5 is halogen, -CN, -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8, -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 ,、C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; in this case, each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl.

[0116] In some embodiments of the compounds of formula (IV), (IVa), or (IVb), R 5 is, -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , optionally substituted with C1-C6 alkyl or C1-C6 haloalkyl.

[0117] In some embodiments of the compound of formula (IV), (IVa) or (IVb), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , or one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or aryl optionally substituted with C1-C6 haloalkyl.

[0118] In some embodiments of the compound of formula (IV), (IVa) or (IVb), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d, -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or C1-C6 haloalkyl is optionally substituted. In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R 5 is -NR 8 C(=O)R 7 In some embodiments of the compounds of formula (IV), (IVa) or (IVb) R 5 is one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or is an aryl optionally substituted with C1-C6 haloalkyl radical.

[0119] In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R 7 is C1-C6 alkyl C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R 7 is C1-C6 alkyl, C1-C6 haloalkyl , C1-C6 deuterated alkyl, or cycloalkyl; wherein alkyl , each of cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (IV), (IVa) or (IVb) R, in some embodiments of the compounds 7 is cycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R is unsubstituted cycloalkyl. 7

[0120] In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R 8 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R 8 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; in which case Each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl.

[0121] In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R 9 and R 10 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (IV), (IVa) or (IVb), R 9 and R 10 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. optionally.

[0122] In some embodiments of the compounds of formula (IV), (IVa) or (IVb), ring C is indole or benzimidazole.

[0123] In some embodiments of the compound of formula (IV), (IVa) or (IVb), each R C is independently deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl.

[0124] In some embodiments of the compound of formula (IV), (IVa) or (IVb), each R C is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl is. In some embodiments of the compound of formula (IV), (IVa) or (IVb), each R C is independently halogen or C1-C6 alkyl.

[0125] In some embodiments of the compound of formula (IV), (IVa) or (IVb), m is 0. Formula (IV), (IVa) or (IVb) in some embodiments of the compound, m is 1. Formula (IV ), (IVa) or (IVb) in some embodiments of the compound, m is 2. Formula (IV), (IVa) or (IVb) in some embodiments of the compound, m is 0 or 1. Formula (IV), (IVa) or (IVb) in some embodiments of the compound, m is 0-2. Formula (IV), (IVa) or (IVb) in some embodiments of the compound, m is 1 or 2. Formula (IV), (IVa) or (IVb) in some embodiments of the compound, m is 1-3.

[0126] As used herein, a compound of formula (V) below, or a pharmaceutically acceptable salt, stereoisomer Isomers or solvates are disclosed: [Chem.] wherein: Ring D is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ; each R D is independently hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NRc R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d ,C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; or two Rs on the same carbon D together form oxo; or two Rs on adjacent atoms D together form cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each optionally substituted with one or more deuterium, oxo, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d ,C 1- C6 alkyl, C 1- C6 deuterated alkyl, or C 1- optionally substituted with C6 haloalkyl; r is from 0 to 4; each Y is independently C or N; R 1 and R 2 are independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated al kyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; R 3 is hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl ; R 4 is hydrogen, deuterium, halogen, -CN, -ORb , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; or R 3 and R 4 together optionally form a substituted ring; L is a bond or -C(=O)-; Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl wherein each of them is optionally substituted with one or more R A ; Each R A is independently deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c Rd , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; or two Rs on the same carbon A together form oxo; each X is independently, -CR x - or -N-; each R Xis independently hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; each R a is independently C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cyclo is alkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; each R b is independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, is cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; each R c and R d is independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated a lkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2-is C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; or R c and R d together with the nitrogen atom to which they are attached, are one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- form a heterocycloalkyl optionally substituted with C6 haloalkyl;

[0127] In some embodiments of the compound of formula (V), L is a bond. In some embodiments of the compound of formula (V), L is -C(=O)-.

[0128] In some embodiments of the compound of formula (V), ring A is heterocycloalkyl or heteroaryl; each optionally substituted with one or more R A . In some embodiments of the compound of formula (V), ring A is a 5-membered heterocycloalkyl or a 5-membered heteroaryl; each optionally substituted with one or more R . In some embodiments of the compound of formula (V), ring A is a heteroaryl optionally substituted with one or more R A . A In some embodiments of the compound of formula (V), each R

[0129] is independently deuterium, halogen, -CN, -OR A , -NR b R c , -C(=O)R d , -C(=O)Ra , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compound of formula (V), each R A is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (V), each R A is independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (V), each R A is independently C1-C6 alkyl.

[0130] In some embodiments of the compound of formula (V), R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compound of formula (V), R 4 is hydrogen or -OR b . In some embodiments of the compound of formula (V), R 4 is -OR b . In some embodiments of the compound of formula (V), R 4 is hydrogen.

[0131] In some embodiments of the compound of formula (V), each X is -N-. In some embodiments of the compound of formula (V), each X is -CH-. In some embodiments of the compound of formula (V), one X is , -N-, and the other X is -CH-.

[0132] In some embodiments of the compound of formula (V), the compound is a compound of the following formula (Va):

Chemical formula

[0133] In some embodiments of the compound of formula (V), the compound is a compound of the following formula (Vb):

Chemical formula

[0134] In some embodiments of the compound of formula (V), (Va) or (Vb), R 3 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (V), (Va) or (Vb), R 3 is hydrogen.

[0135] In some embodiments of the compound of formula (V), (Va) or (Vb), R 1 and R 2 are independently , hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (V), (Va) or (Vb), R 1 and R 2 are independently hydrogen , or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (V), (Va) or (Vb), R is hydrogen. In some embodiments of the compound of formula (V), (Va) or (Vb), R 1 is hydrogen. In some embodiments of the compound of formula (V), (Va) or (Vb), R is 2is C1-C6 alkyl or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (V), (Va) or (Vb), R 2 is C1-C6 deuterated alkyl.

[0136] In some embodiments of the compounds of formula (V), (Va), or (Vb), ring D is heterocycloalkyl or heteroaryl.

[0137] In some embodiments of the compounds of formula (V), (Va) or (Vb),

Chemical formula

[0138] In some embodiments of the compounds of formula (V), (Va) or (Vb), each R D is independently hydrogen, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, cycloalkyl, or heterocycloalkyl. In some embodiments of the compounds of formula (V), (Va) or (Vb), each R D is independently hydrogen, deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl. In some embodiments of the compounds of formula (V), (Va) or (Vb), one part of the embodiments, each R D is independently hydrogen or cycloalkyl.

[0139] In some embodiments of the compounds of formula (V), (Va) or (Vb), r is 0. In formula (V ) In some embodiments of the compound of (V), (Va) or (Vb), r is 1. In some embodiments of the compound of formula (V), (Va) or (Vb), r is 2. In some embodiments of the compound of formula (V), (Va) or (Vb), r is from 0 to 2. In formula (V), (Va ) In some embodiments of the compound, r is 0 or 1. In formula (V), (Va ) In some embodiments of the compound, r is 1 or 2. In formula (V), (Va ) In some embodiments of the compound, r is from 1 to 3.

[0140] In some embodiments of the compound of formula (V), (Va) or (Vb), r' is 0. In some embodiments of the compound of formula (V), (Va) or (Vb), r' is 1. In formula (V), (Va) or (Vb), in some embodiments of the compound, r' is 2. In some embodiments of the compound of formula (V), (Va) or (Vb), r' is from 0 to 2. In formula (V), (Va or (Vb), in some embodiments of the compound, r' is 0 or 1. In formula (V), (Va) or (Vb), in some embodiments of the compound, r' is 1 or 2. In formula (V), (Va ) or (Vb), in some embodiments of the compound, r' is from 1 to 3.

[0141] Disclosed herein is a compound of the following formula (VI), or a pharmaceutically acceptable salt, stereoisomer or solvate thereof:

Chemical formula

[0142] In some embodiments of the compound of formula (VI), L is a bond. In some embodiments of the compound of formula (VI), L is -C(=O)-.

[0143] In some embodiments of the compound of formula (VI), ring A is heterocycloalkyl or hetero aryl; each with one or more R Ais optionally substituted. In some embodiments of the compound of formula (VI), ring A is a 5-membered heterocycloalkyl or a 5-membered heteroaryl; each one or more R A is optionally substituted. In some embodiments of the compound of formula (VI), ring A is a one or more R A optionally substituted heteroaryl.

[0144] In some embodiments of the compound of formula (VI), each R A is independently deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compound of formula (VI), each R A is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (VI), each R A is independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (VI), each R A is independently C1-C6 alkyl.

[0145] In some embodiments of the compound of formula (VI), R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NRc R d 、 C 1- C6 alkyl, C 1- C6 halo alkyl, or C 1- C6 deuterated alkyl. Some embodiments of the compound of formula (VI) in which, R 4 is hydrogen or -OR b . Some embodiments of the compound of formula (VI) in which, R 4 is -OR b . Some embodiments of the compound of formula (VI) in which, R 4 is hydrogen.

[0146] In some embodiments of the compound of formula (VI), X is -CH-. Some of the compound of formula (VI) in the embodiment, X is -N-.

[0147] In some embodiments of the compound of formula (VI), the compound is a compound of the following formula (VIa) :

Chemical formula

[0148] In some embodiments of the compound of formula (VI), the compound is a compound of the following formula (VIb) :

Chemical formula

[0149] In some embodiments of the compound of formula (VI), (VIa) or (VIb), R 3 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (VI), (VIa) or (VIb), R 3 is hydrogen.

[0150] In some embodiments of the compound of formula (VI), (VIa) or (VIb), R 1 and R 2is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (VI), (VIa) or (VIb), R 1 and R 2 are independently hydrogen, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (VI), (VIa) or (VIb), R 1 is hydrogen. In some embodiments of the compounds of formula (VI), (VIa) or (VIb), R 2 is C1-C6 alkyl, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (VI), (VIa) or (VIb), R 2 is C1-C6 deuterated al kyl.

[0151] In some embodiments of the compounds of formula (VI), (VIa) or (VIb), L 2 is a bond.

[0152] In some embodiments of the compounds of formula (VI), (VIa) or (VIb), ring E is cycloal kyl, heterocycloalkyl or aryl; each optionally substituted with one or more R E s.

[0153] In some embodiments of the compounds of formula (VI), (VIa) or (VIb), ring E is aryl optionally substituted with one or more R E s.

[0154] In some embodiments of the compounds of formula (VI), (VIa) or (VIb), each R E is independently deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alky Ru, C 1- C6 haloalkyl, or C 1- is C6 deuterated alkyl.

[0155] In some embodiments of the compounds of formula (VI), (VIa) or (VIb), each R E is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl is.

[0156] In some embodiments of the compounds of formula (VI), (VIa) or (VIb), each R E is independently halogen.

[0157] Disclosed herein are compounds of formula (VII) below, or pharmaceutically acceptable salts, stereoisomers or solvates thereof:

Chemical formula

[0158] In some embodiments of the compound of formula (VII), L is a bond. In one embodiment of the compound of formula (VII), L is -C(=O)-.

[0159] In some embodiments of the compound of formula (VII), ring A is heterocycloalkyl or heteroaryl; each optionally substituted with one or more R A . In some embodiments of the compound of formula (VII), ring A is a 5-membered heterocycloalkyl or a 5-membered heteroaryl; each optionally substituted with one or more R . In some embodiments of the compound of formula (VII), ring A is heteroaryl optionally substituted with one or more R A . A

[0160] In some embodiments of the compound of formula (VII), each R A is independently deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- ​It is a C6 deuterated alkyl. In some embodiments of the compound of formula (VII), each R A is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (VII), each R A is independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (VII), each R A is independently C1-C6 alkyl.

[0161] In some embodiments of the compound of formula (VII), R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compound of formula (VII), R 4 is hydrogen or -OR b . In some embodiments of the compound of formula (VII), R 4 is -OR b . In some embodiments of the compound of formula (VII), R 4 is hydrogen.

[0162] In some embodiments of the compound of formula (VII), X is -CH-. In some embodiments of the compound of formula (VII), X is -N-. In some embodiments of the compound of formula (VII), the compound is a compound of formula (VIIa) below.

[0163] In some embodiments of the compound of formula (VII), the compound is a compound of the following formula (VIIa).

Chemical formula

[0164] In some embodiments of the compound of formula (VII), the compound is a compound of formula (VIIb) below.

Chemical formula

[0165] In some embodiments of the compound of formula (VII), (VIIa) or (VIIb), R 3 is hydrogen or is C1-C6 alkyl. In some embodiments of the compound of formula (VII), (VIIa) or (VIIb), R 3 is hydrogen.

[0166] In some embodiments of the compound of formula (VII), (VIIa) or (VIIb), R 5 is halogen , -CN, -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; in this case, each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a, -C(=O)OR b , -C(=O)NR c R d 、C 1- C6 alkyl, or C 1- C6 haloalkyl, optionally substituted.

[0167] In some embodiments of the compounds of formula (VII), (VIIa), or (VIIb), R 5 is -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl ; wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or optionally substituted with C1-C6 haloalkyl substituted.

[0168] In some embodiments of the compounds of formula (VII), (VIIa) or (VIIb), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , or one or more oxo, deuterium, halogen, -CN, -OR b, -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d is aryl optionally substituted with C1-C6 alkyl or C1-C6 haloalkyl.

[0169] In some embodiments of the compounds of formula (VII), (VIIa), or (VIIb), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , cycloalkyl, heterocycloalkyl, aryl or hetero aryl; wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or C1-C6 halo alkyl optionally substituted. In some embodiments of the compounds of formula (VII), (VIIa) or (VIIb), R 5 is -NR 8 C(=O)R 7 In some embodiments of the compounds of formula (VII), (VIIa) or (VIIb), R 5 is one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or C1-C6 haloalkyl optionally substituted. is the aryl to be replaced.

[0170] In some embodiments of the compounds of formula (VII), (VIIa) or (VIIb), R 7 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (VII), (VIIa) or (VIIb), R 7 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (VII), (VIIa) or (VIIb), R 7 is cycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (VII), (VIIa) or (VIIb), R 7 is unsubstituted cycloalkyl.

[0171] In some embodiments of the compounds of formula (VII), (VIIa) or (VIIb), R 8is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (VII), (VIIa) or (VIIb), R 8 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl.

[0172] In some embodiments of the compounds of formula (VII), (VIIa) or (VIIb), R 9 and R 10 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cyclo alkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl substituted. In some embodiments of the compounds of formula (VII), (VIIa) or (VIIb), R 9 and R 10independently is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; in which case each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl .

[0173] In some embodiments of the compounds of formula (VII), (VIIa), or (VIIb), R 14 is hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, or C 1- C6 alkyl(cycloalkyl). In some embodiments of the compounds of formula (VII), (VIIa) or (VIIb), R 14 is C1-C6 alkyl or C1-C6 alkyl(cycloalkyl).

[0174] Disclosed herein are compounds of formula (VIII) below, or pharmaceutically acceptable salts, stereoisomers or solvates thereof:

Chemical formula

[0175] In some embodiments of the compound of formula (VIII), L is a bond. In the compound of formula (VIII) In some embodiments, L is -C(=O)-.

[0176] In some embodiments of the compound of formula (VIII), ring A is heterocycloalkyl or hetero aryl; each optionally substituted with one or more R A In some embodiments of the compound of formula (VIII), ring A is a 5-membered heterocycloalkyl or 5-membered heteroaryl; each optionally substituted with one or more R A In some embodiments of the compound of formula (VIII), ring A is one or more R Ais a heteroaryl optionally substituted therein.

[0177] In some embodiments of the compound of formula (VIII), each R A is independently deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compound of formula (VIII), each R A is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (VIII), each R A is independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (VIII) each R A is independently C1-C6 alkyl.

[0178] In some embodiments of the compound of formula (VIII), R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compound of formula (VIII) R4 is hydrogen or -OR b In some embodiments of the compound of formula (VIII), R 4 is -OR b In some embodiments of the compound of formula (VIII), R 4 is hydrogen.

[0179] In some embodiments of the compound of formula (VIII), X is -CH-. In some embodiments of the compound of formula (VIII), X is -N-.

[0180] In some embodiments of the compound of formula (VIII), the compound is a compound of the following formula (VIIIa).

Chemical formula

[0181] In some embodiments of the compound of formula (VIII), the compound is a compound of the following formula (VIIIb).

Chemical formula

[0182] In some embodiments of the compound of formula (VIII), (VIIIa) or (VIIIb), R 5 is halogen, -CN, -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C2- C6 alkenyl, C 2- is C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- is C6 alkyl, or C 1- is optionally substituted with C6 haloalkyl.

[0183] In some embodiments of the compounds of formula (VIII), (VIIIa), or (VIIIb), R 5 is -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , is cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or is optionally substituted with C1-C6 haloalkyl.

[0184] In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , or one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or aryl optionally substituted with C1-C6 haloalkyl.

[0185] In some embodiments of the compounds of formula (VIII), (VIIIa), or (VIIIb), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or C1-C6 halo alkyl optionally substituted with alkyl. In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), R 5 is -NR 8 C(=O)R 7 . In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), R of the compound​5 is one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or C1-C6 haloalkyl, and is optionally substituted aryl.

[0186] In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), R 7 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of the alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), R 7 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein in this case each of the alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), R 7 is one or more oxo, deuterium, It is cycloalkyl optionally substituted with halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), R 7 is unsubstituted cycloalkyl .

[0187] In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), R 8 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, hetero cycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), R 8 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl.

[0188] In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), R 9 and R 10 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cyc Lower alkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl optionally substituted. In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), R 9 and R 10 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 halo alkyl optionally substituted.

[0189] In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), L 3 is -O-. In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), L 3 is -NH-.

[0190] In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), R 15 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl.

[0191] In some embodiments of the compounds of formula (VIII), (VIIIa) or (VIIIb), L 4 is -NR 3 -. is.

[0192] In some embodiments of the compound of formula (VIII), (VIIIa) or (VIIIb), R 3 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (VIII), (VIIIa) or (VIIIb), R is hydrogen. 3

[0193] In some embodiments of the compound of formula (VIII), (VIIIa) or (VIIIb), L 4 is -C(=O)-.

[0194] The following compound of formula (IX), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

Chemical formula

[0195] In some embodiments of the compound of formula (IX), L is a bond. Some of the compounds of formula (IX) In an embodiment, L is -C(=O)-.

[0196] In some embodiments of the compound of formula (IX), ring A is heterocycloalkyl or hetero aryl; each optionally substituted with one or more R A s. In some embodiments of the compound of formula (IX), ring A is a 5-membered heterocycloalkyl or a 5-membered heteroaryl; each optionally substituted with one or more R A s. In some embodiments of the compound of formula (IX), ring A is a heteroaryl optionally substituted with one or more R s. A

[0197] In some embodiments of the compound of formula (IX), each R A is independently deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- 6-alkyl, C 1- 6-haloalkyl, or C 1- 6-deuterated alkyl. In some embodiments of the compound of formula (IX), each R A is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (IX), each R A is independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (IX), each R A is independently C1-C6 alkyl.

[0198] In some embodiments of the compound of formula (IX), R 4 is hydrogen, deuterium, halogen, -CN, -ORb , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d 、C 1- C6 alkyl, C 1- C6 ha lower alkyl, or C 1- is C6 deuterated alkyl. Some embodiments of the compound of formula (IX) in, R 4 is hydrogen or -OR b . In some embodiments of the compound of formula (IX), R 4 is -OR b . In some embodiments of the compound of formula (IX), R 4 is hydrogen.

[0199] In some embodiments of the compound of formula (IX), X is -CH-. Some of the compound of formula (IX) in the embodiment, X is -N-.

[0200] In some embodiments of the compound of formula (IX), the compound is a compound of the following formula (IXa) :

Chemical formula

[0201] In some embodiments of the compound of formula (IX), the compound is a compound of the following formula (IXb) :

Chemical formula

[0202] In some embodiments of the compound of formula (IX), (IXa) or (IXb), R 3is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (IX), (IXa) or (IXb), R 3 is hydrogen.

[0203] In some embodiments of the compound of formula (IX), (IXa) or (IXb), R 5 is halogen, -CN, -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or is heteroaryl; in which case each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, or C 1- is optionally substituted with C6 haloalkyl.

[0204] In some embodiments of the compound of formula (IX), (IXa), or (IXb), R 5 is -OR 8 , -NR 9 R10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or optionally substituted with C1-C6 haloalkyl is.

[0205] In some embodiments of the compound of formula (IX), (IXa) or (IXb), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , or one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or optionally substituted with C1-C6 haloalkyl is aryl.

[0206] In some embodiments of the compound of formula (IX), (IXa), or (IXb), R 5 is -OR 8, -NR 9 R 10 , -NR 8 C(=O)R 7 、 cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or C1-C6 haloalkyl optionally substituted with. In some embodiments of the compounds of formula (IX), (IXa) or (IXb), R 5 is -NR 8 C(=O)R 7 is. In some embodiments of the compounds of formula (IX), (IXa) or (IXb) in, R 5 is one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or C1-C6 haloalkyl optionally substituted ar yl.

[0207] In some embodiments of the compounds of formula (IX), (IXa) or (IXb), R 7 is C1-C6 alky is C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (IX), (IXa) or (IXb), R 7 is C1-C6 alkyl, C1-C6 haloalkyl C1-C6 deuterated alkyl, or cycloalkyl; wherein alkyl cycloalkyl, and heterocycloalkyl are each independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (IX), (IXa) or (IXb) R 7 is cycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 halo alkyl. In some embodiments of the compounds of formula (IX), (IXa) or (IXb), R 7 is unsubstituted cycloalkyl.

[0208] In some embodiments of the compounds of formula (IX), (IXa) or (IXb), R 8 is hydrogen, C1-C6 is alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (IX), (IXa) or (IXb), R 8 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (IX), (IXa) or (IXb), R

[0209] and R 9 are independently 10 hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (IX), (IXa) or (IXb), R and R are 9 and R 10 are independently, hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl optionally substituted.

[0210] In some embodiments of the compounds of formula (IX), (IXa), or (IXb), ring F is heterocyclo alkyl.

[0211] In some embodiments of the compounds of formula (IX), (IXa) or (IXb),

Chemical formula

[0212] In some embodiments of the compounds of formula (IX), (IXa) or (IXb), each R F is independently hydrogen, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- 1-C6 alkyl, C 1- 1-C6 haloalkyl, or C 1- 1-C6 deuterated alkyl. In some embodiments of the compounds of formula (IX), (IXa ) or (IXb), each R F is independently hydrogen, deuterium, halo gen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl.

[0213] In some embodiments of the compound of formula (IX), (IXa) or (IXb), p is 0. Formula (IX), (IXa) or (IXb), in some embodiments, p is 1. Formula (IX ), (IXa) or (IXb), in some embodiments, p is 2. Formula (IX), (IXa) or (IXb), in some embodiments, p is from 0 to 2. Formula (IX), (IXa) or (IXb), in some embodiments, p is 0 or 1. Formula (IX), (IXa) or (IXb), in some embodiments, p is 1 or 2. Formula (IX), (IXa) or (IXb), in some embodiments, p is from 1 to 3.

[0214] As used herein, the following compound of formula (X), or a pharmaceutically acceptable salt, solvate adduct, or stereoisomer thereof is disclosed: [Chemical formula] Wherein: L 5 is an optionally substituted by one or more R L5 saturated or unsaturated straight-chain aliphatic chain having 1 to 10 carbon atoms, wherein in this case 1 to 5 carbon atoms are optionally replaced by -NH-, -N(CH3)-, -O-, -S-, -S(=O)-, -S(=O)2-, or -P(=O)-; Each R L5 is independently deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b, -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C6 alkyl , C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; or two Rs on the same carbon atom together form oxo; L5 R R 12 is -C(=O)NR 1 R 2 or -L 1- R 13 ; R 1 and R 2 are independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated al kyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; L 1 is -O-, -NH-, or -N(CH3)-; R 13 is C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxy alkyl, C 1-C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl , heterocycloalkyl, aryl or heteroaryl; in which case, each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, or C 1- C6 halo alkyl optionally substituted; R 3 is hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl ; R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)Ra , -NR b C(=O)OR b 、C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; or R 3 and R 4 together optionally form a ring; L is a bond or -C(=O)-; Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ; each of which is optionally substituted with one or more R A ; Each R A is independently deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1-C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; or two Rs on the same carbon A together form oxo; X is, -CR x - or -N-; R X is hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NRb C(=O)OR b 、 C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; each R a is independently, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cyclo alkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- C6 haloalkyl; each R b is independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, is cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; each R c and R d is independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; or R c and R d together with the nitrogen atom to which they are attached form a heterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- C6 haloalkyl;

[0215] In some embodiments of the compound of formula (X), L is a bond. In some In an embodiment, L is -C(=O)-.

[0216] In some embodiments of the compound of formula (X), ring A is heterocycloalkyl or heteroaryl; each optionally substituted with one or more R A s. In some embodiments of the compound of formula (X), ring A is a 5-membered heterocycloalkyl or a 5-membered heteroaryl; each optionally substituted with one or more R s. In some embodiments of the compound of formula (X), ring A is a heteroaryl optionally substituted with one or more R s. A In some embodiments of the compound of formula (X), each R A is independently deuterium, halogen, -CN, -OR

[0217] In some embodiments of the compound of formula (X), each R A is independently deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- 6-alkyl, C 1- 6-haloalkyl, or C 1- 6-deuterated alkyl. In some embodiments of the compound of formula (X), each R A is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (X), each R A is independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (X), each R A is independently C1-C6 alkyl.

[0218] In some embodiments of the compound of formula (X), R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)Ra , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compound of formula (X), R 4 is hydrogen or -OR b . In some embodiments of the compound of formula (X), R 4 is -OR b . . In some embodiments of the compound of formula (X), R 4 is hydrogen.

[0219] . In some embodiments of the compound of formula (X), X is -CH-. In some embodiments of the compound of formula (X), X is -N-.

[0220] . In some embodiments of the compound of formula (X), the compound is of the formula

Chemical formula

Chemical formula

[0221] . In some embodiments of the compound of formula (X), the compound is a compound of the following formula (Xa):

Chemical formula

[0222] . In some embodiments of the compound of formula (X), the compound is a compound of the following formula (Xb):

Chemical formula

[0223] In some embodiments of the compound of formula (X), the compound is a compound of the following formula (Xa-1) :

Chemical formula

[0224] In some embodiments of the compound of formula (X), the compound is a compound of the following formula (Xb-1) :

Chemical formula

[0225] In some embodiments of the compound of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), R 3 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), R 3 is hydrogen.

[0226] In some embodiments of the compound of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), R 12 is -C(=O)NR 1 R 2 .

[0227] In some embodiments of the compound of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), R 1 and R 2 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), R 1 and R 2 are independently hydrogen, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), R 1is hydrogen. In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1) form, R 2 is C1-C6 alkyl or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (X), (Xa) , (Xa-1), (Xb) or (Xb-1), R 2 is C1-C6 deuterated alkyl.

[0228] In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), R 12 is -L 1 -R 13 wherein.

[0229] In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), L 1 is -NH-. In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), L 1 is -O- or -NH-.

[0230] In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), R 13 is C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl.

[0231] In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), L 5 is a saturated straight-chain aliphatic chain having 1 to 8 carbon atoms optionally substituted with one or more R L5 wherein in this case 1, 2, or 3 carbon atoms are optionally replaced by -NH-, -N(CH3)-, -O-, -S-, -S(=O)-, -S(=O) 2- , or -P(=O)-. In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), L 5is a saturated straight-chain aliphatic chain having 1 to 8 carbon atoms optionally substituted with one or more R L5 and in this case 1, 2, or 3 carbon atoms are optionally replaced with -NH-, -N(CH3)-, or -O-. In some embodiments of the compounds of formula (X) , (Xa), (Xa-1), (Xb) or (Xb-1), L 5 is a saturated straight-chain aliphatic chain having 1 to 8 carbon atoms optionally substituted with one or more R L5 and in this case 1, 2, or 3 carbon atoms are optionally replaced with -NH- or -O-.

[0232] In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), L 5 is a saturated straight-chain aliphatic chain having 1 to 8 carbon atoms and in this case 1, 2, or 3 carbon atoms are optionally replaced with -NH-, -N(CH3)-, -O-, -S-, -S(=O)-, or -S(=O)2-. In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1) L 5 is a saturated straight-chain aliphatic chain having 1 to 8 carbon atoms and in this case 1, 2, or 3 carbon atoms are optionally replaced with -NH-, -N(CH3)-, or -O-. In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), L 5 is a saturated straight-chain aliphatic chain having 1 to 8 carbon atoms and in this case 1, 2, or 3 carbon atoms are optionally replaced with -NH- or -O-.

[0233] In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), L 5 is a saturated straight-chain aliphatic chain having 1 to 8 carbon atoms optionally substituted with one or more R L5is an unsaturated straight-chain aliphatic chain having 1 to 8 carbon atoms, optionally replaced, in which case 1, 2, or 3 carbon atoms are optionally replaced by -NH-, -N(CH3)-, -O-, -S-, -S(=O)-, or -S(=O)2-. In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb ), or (Xb-1), L 5 is an unsaturated straight-chain aliphatic chain having 1 to 8 carbon atoms, optionally substituted with one or more R L5 and optionally replaced by -NH-, -N(CH3)-, or -O-. In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), L is an unsaturated straight-chain aliphatic chain having 1 to 8 carbon atoms, optionally substituted with one or more R 5 and optionally replaced by -NH- or -O-. L5 In this case, 1, 2, or 3 carbon atoms are optionally replaced by -NH- or -O-. In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), L

[0234] is an unsaturated straight-chain aliphatic chain having 1 to 8 carbon atoms, optionally replaced, in which case 1, 2, 5 or 3 carbon atoms are optionally replaced by -NH-, -N(CH3)-, -O-, -S-, -S(=O)-, -S(=O)2-, or -P(=O)-. In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), L is an unsaturated straight-chain aliphatic chain having 1 to 8 carbon atoms, optionally replaced, in which case 1, 2, or 3 carbon atoms are optionally replaced by -NH-, -N(CH3)-, or -O-. In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), L 5 is an unsaturated straight-chain aliphatic chain having 1 to 8 carbon atoms, optionally replaced, in which case 1, 2, or 3 carbon atoms are optionally replaced by -NH-, -N(CH3)-, or -O-. In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), L is 5is an unsaturated straight-chain aliphatic chain having 1 to 8 carbon atoms, in which case 1, 2, or 3 carbon atoms are optionally replaced by -NH-, or -O-.

[0235] In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), each R L5 is independently deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In the formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), in some embodiments of the compounds, each R L5 is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deutero ated alkyl. In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), each R L5 is independently deuterium or halogen.

[0236] In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), two Rs on the same carbon atom together form an oxo. L5

[0237] In some embodiments of the compounds of formula (X), (Xa), (Xa-1), (Xb) or (Xb-1), L 5 is

Chemical formula

[0238] ​In this specification, compounds of the following formula (XI), or pharmaceutically acceptable salts, solvates, or stereoisomers thereof, are disclosed:

Chemical formula

[0239] In some embodiments of the compound of formula (XI), L is a bond. In some embodiments of the compound of formula (XI), L is -C(=O)-.

[0240] In some embodiments of the compound of formula (XI), ring A is heterocycloalkyl or hetero aryl; each optionally substituted with one or more R A In some embodiments of the compound of formula (XI), ring A is a 5-membered heterocycloalkyl or a 5-membered heteroaryl; each optionally substituted with one or more R A In some embodiments of the compound of formula (XI), ring A is a heteroaryl optionally substituted with one or more R In some embodiments of the compound of formula (XI), each R A is independently deuterium, halogen, -CN, -OR

[0241] In some embodiments of the compound of formula (XI), each R A is independently deuterium, halogen, -CN, -OR b , -NRc R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d 、C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compound of formula (XI), each R A is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (XI), each R A is independently halogen or C1-C6 alkyl. In some embodiments of the compound of formula (XI), each R A is independently C1-C6 alkyl.

[0242] In some embodiments of the compound of formula (XI), R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d 、C 1- C6 alkyl, C 1- C6 ha loalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compound of formula (XI) wherein, R 4 is hydrogen or -OR b . In some embodiments of the compound of formula (XI), R 4 is -OR b . In some embodiments of the compound of formula (XI), R 4 is hydrogen.

[0243] In some embodiments of the compound of formula (XI), X is -CH-. Some of the compounds of formula (XI) in the embodiments, X is -N-.

[0244] In some embodiments of the compound of formula (XI), the compound is a compound of the following formula (XIa). [Chemical formula]

[0245] In some embodiments of the compound of formula (XI), the compound is a compound of the following formula (XIb). [Chemical formula]

[0246] In some embodiments of the compound of formula (XI), (XIa) or (XIb), R 3 is hydrogen or C1-C6 alkyl. In some embodiments of the compound of formula (XI), (XIa) or (XIb), R 3 is hydrogen.

[0247] In some embodiments of the compound of formula (XI), (XIa) or (XIb), R 5 is halogen, -CN, -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 2-C6 Alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; in this case, each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d 、C 1- C6 alkyl, or C 1- C6 haloalkyl optionally substituted.

[0248] In some embodiments of the compounds of formula (XI), (XIa) or (XIb), R 5 is, -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; in this case, each of cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d 、C 1- C6 alkyl, or C 1-Optionally substituted with C6 haloalkyl is.

[0249] In some embodiments of the compounds of formula (XI), (XIa) or (XIb), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , or one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or aryl optionally substituted with C1-C6 haloalkyl is.

[0250] In some embodiments of the compounds of formula (XI), (XIa) or (XIb), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or optionally substituted with C1-C6 haloalkyl. In some embodiments of the compounds of formula (XI), (XIa) or (XIb), R is -NR 5 C(=O)R 8 is. In some embodiments of the compounds of formula (XI), (XIa) or (XIb) 7 ​ is R 5 is one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d and is an aryl optionally substituted by C1-C6 alkyl, or C1-C6 haloalkyl .

[0251] In some embodiments of the compounds of formula (XI), (XIa) or (XIb), R 7 is C1-C6 alkyl C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted by one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (XI), (XIa) or (XIb), R 7 is C1-C6 alkyl, C1-C6 haloalkyl C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl cycloalkyl, and heterocycloalkyl is independently optionally substituted by one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (XI), (XIa) or (XIb) R in 7is cycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (XI), (XIa) or (XIb), R is unsubstituted cycloalkyl. 7 In some embodiments of the compounds of formula (XI), (XIa) or (XIb), R

[0252] is hydrogen, C1-C6 8 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of the alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (XI), (XIa) or (XIb), R 8 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein in each case each of the alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl.

[0253] In some embodiments of the compounds of formula (XI), (XIa) or (XIb), R 9 and R 10 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl is a kill, heterocycloalkyl, aryl or heteroaryl; in this case, each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl In some embodiments of the compounds of formula (XI), (XIa) or (XIb), R 9 and R 10 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; in this case, each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl optionally substituted.

[0254] In some embodiments of the compounds of formula (XI), (XIa) or (XIb), L 6 is a saturated straight-chain aliphatic chain having 1 to 8 carbon atoms optionally substituted with one or more R L6 ; in this case wherein 1, 2, or 3 carbon atoms are optionally replaced by -NH-, -N(CH3)-, -O-, -S-, -S(=O)-, or -S(=O)2-. In some embodiments of the compounds of formula (XI), (XIa) or (XIb), L 6 is a saturated straight-chain L6 aliphatic chain having 1 to 8 carbon atoms optionally substituted with one or more R ; in this case, 1, 2, or 3 carbon atoms are optionally replaced by -NH-, -N(CH3)-, or -O-. In some embodiments of the compounds of formula (XI), (XIa) or (XIb), L 6 is one or more R L6is a saturated straight-chain aliphatic chain having 1 to 8 carbon atoms, optionally replaced, in which case 1, 2, or 3 carbon atoms are optionally replaced by -NH- or -O-.

[0255] In some embodiments of the compound of formula (XI), (XIa) or (XIb), L 6 is a saturated straight-chain aliphatic chain having 1 to 8 carbon atoms, in which case 1, 2, or 3 carbon atoms are optionally replaced by -NH-, -N(CH3)-, -O-, -S-, -S(=O)-, or -S(=O)2-. In some embodiments of the compound of formula (XI), (XIa) or (XIb), L is a saturated straight-chain aliphatic chain having 1 to 8 carbon atoms, in which case 1, 2, or 3 carbon atoms are optionally replaced by -NH-, -N(CH3)-, or -O-. In some embodiments of the compound of formula (XI), (XIa) or (XIb) 6 L is a saturated straight-chain aliphatic chain having 1 to 8 carbon atoms, in which case 1, 2, or 3 carbon atoms are optionally replaced by -NH- or -O-. In some embodiments of the compound of formula (XI), (XIa) or (XIb) L is a saturated straight-chain aliphatic chain having 1 to 8 carbon atoms, in which case 1, 2, or 3 carbon atoms are optionally replaced by -NH- or -O-. 6

[0256] In some embodiments of the compound of formula (XI), (XIa) or (XIb), L 6 is an unsaturated straight-chain aliphatic chain having 1 to 8 carbon atoms, optionally substituted with one or more R L6 wherein 1, 2, or 3 carbon atoms are optionally replaced by -NH-, -N(CH3)-, -O-, -S-, -S(=O)-, -S(=O) 2, or -P(=O)-. In some embodiments of the compound of formula (XI), (XIa) or (XIb), L 2- is an unsaturated straight-chain aliphatic chain having 1 to 8 carbon atoms, optionally substituted with one or more R and having 1 to 8 carbon atoms, in which case 1, 2, or 3 carbon atoms are optionally replaced by -NH-, -N(CH3)-, -O-, -S-, -S(=O)-, -S(=O) 6 In some embodiments of the compound of formula (XI), (XIa) or (XIb), L L6 is an unsaturated straight-chain aliphatic chain having 1 to 8 carbon atoms, optionally substituted with one or more R ​​​is an unsaturated straight-chain aliphatic chain, in which case 1, 2, or 3 carbon atoms are optionally , -NH-, -N(CH3)-, or -O-. In some embodiments of the compound of formula (XI), (XIa), or (XIb), L is an unsaturated straight-chain aliphatic chain having 1 to 8 carbon atoms optionally substituted with one or more R 6 s, in which case 1, 2, or 3 carbon atoms are optionally L6 substituted with -NH- or -O-. In some embodiments of the compound of formula (XI), (XIa), or (XIb), L is an unsaturated straight-chain aliphatic chain having 1 to 8 carbon atoms, in which case 1, 2, or 3 carbon atoms are optionally

[0257] substituted with -NH-, -N(CH3)-, -O-, -S-, -S(=O)-, -S(=O)2-, or -P(=O)-. In some embodiments of the compound of formula (XI), (XIa), or (XIb), L 6 is an unsaturated straight-chain aliphatic chain having 1 to 8 carbon atoms, in which case 1, 2, or 3 carbon atoms are optionally substituted with -NH-, -N(CH3)-, -O-, -S-, -S(=O)-, -S(=O)2-, or -P(=O)-. In some embodiments of the compound of formula (XI), (XIa), or (XIb), L 6 is an unsaturated straight-chain aliphatic chain having 1 to 8 carbon atoms, in which case 1, 2, or 3 carbon atoms are optionally substituted with -NH-, -N(CH3)-, or -O-. In some embodiments of the compound of formula (XI), (XIa), or (XIb), L 6 is an unsaturated straight chain aliphatic chain having 1 to 8 carbon atoms, in which case 1, 2, or 3 carbon atoms are optionally substituted with -NH-, or -O-.

[0258] In some embodiments of the compound of formula (XI), (XIa), or (XIb), each R L6 is independently deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b, -C(=O)NR c R d 、 C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compounds of formula (XI), (XIa) or (XIb), each R is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (XI), (XIa) or (XIb), each R L6 is independently deuterium or halogen. L6

[0259] In some embodiments of the compounds of formula (XI), (XIa) or (XIb), two Rs on the same carbon atom together form an oxo. L6

[0260] In some embodiments of the compounds of formula (XI), (XIa) or (XIb), L 6 is

Chemical formula

[0261] Disclosed herein are compounds of the following formula (XII), or pharmaceutically acceptable salts, solvates, or stereoisomers thereof:

Chemical formula

[0262] In this specification, a compound of formula (XII) below, or a pharmaceutically acceptable salt thereof, stand Tautomers or solvates are disclosed: [Chemical formula] In the formula: Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 16 is -C(=O)NR 1 R 2 , -C(=N-CN)NR 1 R 2 , -P(=O)R 1 R 2 , or -C(=O)R 11 ; R 1 and R 2 are independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; R 3 is hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl; ; R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NRc R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b 、-P(=O)R b R b 、C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; or R 3 and R 4 together optionally form a substituted ring; L is a bond or -C(=O)-; Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl wherein each of them is optionally substituted with one or more R A ; Each R A is independently deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NRb C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b 、C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently, one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d 、C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; or two R's on the same carbon A together form oxo; or -L-ring A is absent; each X is independently, -CR x - or -N-; each R X is independently hydrogen, deuterium, halogen,, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a, -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b , -NR b 、C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; R 5 is halogen, -CN, -OR 8 , -SR 8 , -S(=O)R 7 , -S(=O)2R 7 , -NO2, -NR 9 R 10 , -NR 8 S(=O)R 7 , -NR 8 S(=O)2R 7 , -S(=O)2NR 9 R 10 , -C(=N-CN)R 7 ,-C(=O)R 7 , -OC(=N-CN)R 7 , -OC(=O)R 7 , -C(=N-CN)OR 8 , -C(=O)OR 8 , -OC(=N-CN)OR 8 , -OC(=O)OR 8 , -C(=N-CN)NR 9 R 10 , -C(=O)NR 9 R 10 , -OC(=N-CN)NR 9 R10 , -OC(=O)NR 9 R 10 , -NR 8 C(=N-CN)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=N-CN)R 7 , -NR 8 C(=N-OH)R 7 , -NR 8 C(=N-CN)OR 8 , -NR 8 C(=O)OR 8 , -NR 8 S(=O)(=NR 8 )R 7 、C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d 、C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 1- C6 heteroalkyl, C 2- C6 alkenyl, C 2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, he teroaryl, C 1- C6 alkyl(cycloalkyl), C 1- C6 alkyl(heterocycloalkyl), C 1- C6 alkyl(aryl), or C 1- C6 alkyl(heteroaryl) optionally substituted; in which case each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo , deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, or C 1- C6 haloalkyl optionally substituted; R 7 is C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; in which case each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- C6 haloal kyl optionally substituted; Each R 8 is independently hydrogen, CN, C 1- C6 alkyl, C 1-C6 haloalkyl, C 1- C6 deuterated alkyl yl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- C6 haloalkyl; R 9 and R 10 are independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, C 1- C6 deuterated alkyl, C 1- C6 haloalkyl, C 1- C6 hydroxyalkyl, C 1- C6 hydroxydeuterated alkyl, cycloalkyl, or heterocycloalkyl; or R 9 and R 10 together with the nitrogen atom to which they are attached, one or more oxo, deuterium a group, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- 6-alkyl, or C 1- forms a heterocycloalkyl optionally substituted with C6-haloalkyl; or R 8 and R 9 together with the atom to which they are attached form one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- 6-alkyl, or C 1- forms a heterocycloalkyl optionally substituted with C6-haloalkyl; R 11 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, C1-C6 hydroxy alkyl, C1-C6 aminoalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl , heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R 11a ; each R 11a is independently deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR cR d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; Each R a is independently C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cyclo alkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- C6 haloalkyl; Each R b is independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, is cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; each R c and R d is independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; or R c and R d together with the nitrogen atom to which they are attached form a heterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- C6 haloalkyl;

[0263] In this specification, a compound of formula (XII) below, or a pharmaceutically acceptable salt, sol A medium or stereoisomer is disclosed: [Chemical formula] Wherein: Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 16 is -C(=O)NR 1 R 2 , -C(=N-CN)NR 1 R 2 , -P(=O)R 1 R 2 , or -C(=O)R 11 ; R 1 and R 2 are independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; R 3 is hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl; ; R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NRc R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b 、-P(=O)R b R b 、C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; or R 3 and R 4 together optionally form a substituted ring; L is a bond or -C(=O)-; Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl wherein each is optionally substituted with one or more R A ; Each R A is independently deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NRb C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b 、C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein alkyl, alkenyl, alk ynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are each independently, one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d 、C 1- C6 alkyl, or C 1- C6 haloalkyl optionally substituted; or two Rs on the same carbon A together form oxo; each X is independently, -CR x - or -N-; each R X is independently hydrogen, deuterium, halogen,, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)ORb , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b 、C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; R 5 is halogen, -CN, -OR 8 , -SR 8 , -S(=O)R 7 , -S(=O)2R 7 , -NO2, -NR 9 R 10 , -NR 8 S(=O)R 7 , -NR 8 S(=O)2R 7 , -S(=O)2NR 9 R 10 , -C(=N-CN)R 7 ,-C(=O)R 7 , -OC(=N-CN)R 7 , -OC(=O)R 7 , -C(=N-CN)OR 8 , -C(=O)OR 8 , -OC(=N-CN)OR 8 , -OC(=O)OR 8 , -C(=N-CN)NR 9 R 10 , -C(=O)NR 9 R 10 , -OC(=N-CN)NR 9 R 10, -OC(=O)NR 9 R 10 , -NR 8 C(=N-CN)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=N-CN)R 7 , -NR 8 C(=N-OH)R 7 , -NR 8 C(=O)R 7 , -NR 8 C(=N-CN)OR 8 , -NR 8 C(=O)OR 8 , -NR 8 S(=O)(=NR 8 )R 7 , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 1- C6 hetero alkyl, C 2-C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1- C6 alkyl(cycloalkyl), C 1- C6 alkyl(heterocycloalkyl), C 1- C6 alkyl(aryl), or C 1- C6 alkyl(heteroaryl), optionally substituted; in which case, alkyl, alkenyl, alkynyl, cyclo alkyl, heterocycloalkyl, aryl and heteroaryl are each independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, or C 1- C6 haloalkyl, optionally substituted; or R X and R 5 together form a ring D optionally substituted with one or more R D ; ring D is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ; each R D is independently hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d, -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b 、 C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d 、 C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl and; or two R's on the same carbon D together form oxo; R 7 is, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- C6 haloalkyl optionally substituted with; each R 8 is independently hydrogen, CN, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 1- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 2- C6 alkyl, or C 1- C6 haloalkyl 1- optionally substituted with; R 9 and R 10 are independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2-is C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, C 1- C6 deuterated alkyl, C 1- C6 haloalkyl, C 1- C6 hydroxyalkyl, C 1- is optionally substituted with C6 hydroxydeuterated alkyl, cycloalkyl, or heterocycloalkyl; or R 9 and R 10 together with the nitrogen atom to which they are attached, are one or more oxo, deuterium element, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- form a heterocycloalkyl optionally substituted with C6 haloalkyl; or R 8 and R 9 together with the atom to which they are attached, are one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- form a heterocycloalkyl optionally substituted with C6 haloalkyl; R 11 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, C1-C6 hydroxy alkyl, C1-C6 aminoalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl , is heterocycloalkyl, aryl or heteroaryl; in which case each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R 11a ; each R 11a is independently deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; each R a is independently C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C2- C6 alkynyl, cyclo alkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; each R b is independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; each R c and R d are independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated a lkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2-is C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo each of alkyl, cycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; or R c and R d together with the nitrogen atom to which they are attached are one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- form a heterocycloalkyl optionally substituted with C6 haloalkyl;

[0264] Disclosed herein are compounds of formula (XII) below, or pharmaceutically acceptable salts, sol vates, or stereoisomers thereof:

Chemical formula

[0265] In some embodiments of the compound of formula (XII), ring B is aryl or heteroaryl. In some embodiments of the compound of formula (XII), ring B is aryl. In some embodiments of the compound of formula (XII), ring B is phenyl. In some embodiments of the compound of formula (XII), ring B is heteroaryl. In some embodiments of the compound of formula (XII), ring B is a 5- or 6-membered heteroaryl. In some embodiments of the compound of formula (XII), ring B is a 6-membered heteroaryl. In some embodiments of the compound of formula (XII), ring B is pyridyl.

[0266] As used herein, the following compound of formula (XII’), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof is disclosed: [Chemical formula] In the formula: R 16 is -C(=O)NR 1 R 2 , -C(=N-CN)NR 1 R 2 , -P(=O)R 1 R 2 or -C(=O)R 11 ; R 1 and R 2 are independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; R 3 is hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl; ; R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NRc R d , -NR b C(=O)R a , -NR b C(=O)OR b 、-P(=O)R b R b 、C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; or R 3 and R 4 together optionally form a substituted ring; L is a bond or -C(=O)-; Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ; each of which is optionally substituted with one or more R A ; Each R A is independently deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NRb C(=O)OR b 、C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d 、C 1- C6 alkyl, or C 1- C6 haloalkyl optionally substituted; or two Rs on the same carbon A together form oxo; each X is independently, -CR x - or -N-; each R X is independently hydrogen, deuterium, halogen,, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c Rd , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b 、C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, or C 2- C6 alkynyl; R 5 is halogen, -CN, -OR 8 , -SR 8 , -S(=O)R 7 , -S(=O)2R 7 , -NO2, -NR 9 R 10 , -NR 8 S(=O)R 7 , -NR 8 S(=O)2R 7 , -S(=O)2NR 9 R 10 , -C(=N-CN)R 7 ,-C(=O)R 7 , -OC(=N-CN)R 7 , -OC(=O)R 7 , -C(=N-CN)OR 8 , -C(=O)OR 8 , -OC(=N-CN)OR 8 , -OC(=O)OR 8 , -C(=N-CN)NR 9 R 10 , -C(=O)NR 9 R 10 , -OC(=N-CN)NR 9 R 10 , -OC(=O)NR 9 R 10 , -NR 8 C(=N-CN)NR 9 R 10 , -NR8 C(=O)NR 9 R 10 , -NR 8 C(=N-CN)R 7 , -NR 8 C(=N-OH)R 7 , -NR 8 C(=O)R 7 , -NR 8 C(=N-CN)OR 8 , -NR 8 C(=O)OR 8 , -NR 8 S(=O)(=NR 8 )R 7 , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 1- C6 hetero alkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1-C6 alkyl(cycloalkyl), C 1- C6 alkyl(heterocycloalkyl), C 1- C6 alkyl(aryl), or C 1- C6 alkyl(heteroaryl), optionally substituted; in which case, each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, or C 1- C6 haloalkyl, optionally substituted; or R X and R 5 together form a ring D optionally substituted with one or more R D ; ring D is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ; each R D is independently hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d, -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl and; or two R's on the same carbon D together form oxo; R 7 is C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein, in this case, each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1- C6 alkyl, or C 1- C6 haloalkyl optionally substituted with; each R 8 is independently hydrogen, CN, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; R 9 and R 10 are independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, C 1- C6 deuterated alkyl, C 1- C6 haloalkyl, C 1- C6 hydroxyalkyl, C1- optionally substituted with C6 hydroxydeuterated alkyl, cycloalkyl, or heterocycloalkyl; or R 9 and R 10 together with the nitrogen atom to which they are attached, form one or more oxo, deuterium ium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- heterocycloalkyl optionally substituted with C6 haloalkyl; or R 8 and R 9 together with the atom to which they are attached, form one or more oxo, deuterium, halo gen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- heterocycloalkyl optionally substituted with C6 haloalkyl; R 11 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, C1-C6 hydroxy alkyl, C1-C6 aminoalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl , heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R 11a ; each R 11a is independently deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O)2R a , -NO2, -NR c R d , -NHS(=O)2R a , -S(=O)2NR c R d, -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- , C6 alkyl, C 1- , C6 haloalkyl, C 1- , C6 deuterated alkyl, C 1- , C6 hydroxyalkyl, C 1- , C6 aminoalkyl, C 2- , C6 alkenyl, or C 2- , C6 alkynyl; Each R a is independently, C 1- , C6 alkyl, C 1- , C6 haloalkyl, C 1- , C6 deuterated alkyl, C 1- , C6 hydroxyalkyl, C 1- , C6 aminoalkyl, C 2- , C6 alkenyl, C 2- , C6 alkynyl, cyclo , alkyl, heterocycloalkyl, aryl or heteroaryl; in which case each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- , C6 alkyl, or C 1- , C6 haloalkyl; Each R b is independently hydrogen, C 1- , C6 alkyl, C 1- , C6 haloalkyl, C 1-C6 deuterated alkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; in this case, each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; each R c and R d are independently hydrogen, C 1- C6 alkyl, C 1- C6 haloalkyl, C 1- C6 deuterated a lkyl, C 1- C6 hydroxyalkyl, C 1- C6 aminoalkyl, C 2- C6 alkenyl, C 2- C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; in this case, each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1- optionally substituted with C6 haloalkyl; or R c and R d together with the nitrogen atom to which they are attached, one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C6 alkyl, or C 1-forms a heterocycloalkyl optionally substituted with C6 haloalkyl;

[0267] In some embodiments of the compound of formula (XII) or (XII'), L is a bond. Formula (XII ) or in some embodiments of the compound of (XII'), L is -C(=O)-.

[0268] In some embodiments of the compound of formula (XII) or (XII'), -L-ring A does not exist.

[0269] In some embodiments of the compound of formula (XII) or (XII'), ring A is heterocycloalkyl or heteroaryl; each optionally substituted with one or more R A . In some embodiments of the compound of formula (XII) or (XII'), ring A is a 5-membered heterocycloalkyl or a 5 -membered heteroaryl; each optionally substituted with one or more R A . In some embodiments of the compound of formula (XII) or (XII'), ring A is heteroaryl optionally substituted with one or more R A .

[0270] In some embodiments of the compound of formula (XII) or (XII'), each R A is independently deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compound of formula (XII) or (XII'), each R Ais independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compound of formula (XII) or (XII'), each R A is independently halogen or C1-C6 alkyl . In some embodiments of the compound of formula (XII) or (XII'), each R A is independently C1-C6 alkyl.

[0271] In some embodiments of the compound of formula (XII), the compound is a compound of the following formula (XIIa).

Chemical formula

[0272] In some embodiments of the compound of formula (XII), the compound is a compound of the following formula (XIIb).

Chemical formula

[0273] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C6 alkyl, C 1- C6 haloalkyl, or C 1- C6 deuterated alkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 4 is hydrogen or -OR bis. In some embodiments of the compound of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 4 is -OR b . In some embodiments of the compound of formula (XII ), (XII’), (XIIa), (XIIb), or (XIIc), R 4 is hydrogen. In some embodiments of the compound of formula (XII), R 4 is -P(=O)R b R b . In some embodiments of the compound of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 4 is -S(=O)2R a .

[0274] In some embodiments of the compound of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), each X is -N-. In some embodiments of the compound of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), each X is -CR X -. In some embodiments of the compound of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), two Xs are -N-, and the other X is -CR X -. In some embodiments of the compound of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), one X is -N- and the other X is -CR X -. In some embodiments of the compound of formula (XII ), (XII’), (XIIa), (XIIb), or (XIIc), each X is -CH-. In some embodiments of the compound of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), two Xs are -N- and the other X is -CH-. In some embodiments of the compound of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), one X is -N- and the other X is -CH-. In some embodiments of the compound of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), one One of the X's is -N-, and the other X's are -CH-. In some embodiments of the compounds of formula (XII), (XII'), (XIIa), (XIIb) , or (XIIc),

Chemical formula

Chemical formula

Chemical formula

[0275] In some embodiments of the compounds of formula (XII), (XII'), (XIIa), (XIIb), or (XIIc), each R X is independently hydrogen, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, C1-C6 hydroxyalkyl, or C1-C6 aminoalkyl. In some embodiments of the compounds of formula (XII), (XII'), (XIIa), (XIIb), or (XIIc), each R X is independently hydrogen, deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (XII), (XII'), (XIIa), (XIIb), or (XIIc), each R X is independently hydrogen, deuterium, or halogen.

[0276] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), [Chemical formula] it is. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), [Chemical formula] it is. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), [Chemical formula] it is.

[0277] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 3 is hydrogen or C1-C6 alkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 3 is hydrogen.

[0278] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 16 is C(=O)NR 1 R 2 or -C(=O)R 11 . In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 16 is -C(=O)NR 1 R 2 . In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 16 is -C(=N-CN)NR 1 R 2 . In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), In some embodiments of the compound of formula (XIIc), R 16 is -P(=O)R 1 R 2 . In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 16 is -C(=O)R 11 .

[0279] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 1 and R 2 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc ), R 1 and R 2 are independently hydrogen, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc ), R 1 and R 2 are independently C1-C6 alkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 1 is hydrogen. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 2 is C1-C6 alkyl, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (XII) , (XII’), (XIIa), (XIIb), or (XIIc), R 2 is C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc ), in some embodiments of the compound of formula (XIIc), R 2 is C1-C6 alkyl.

[0280] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 11 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, cycloalkyl, heterocycloalkyl, a ryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R 11a s. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 11 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, cycloalkyl, or heterocycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R 11a s. In some embodiments of the compounds of formula (XII) , (XII’), (XIIa), (XIIb), or (XIIc), R 11 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, or heterocycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R 11a s. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 11 is C1-C6 alkyl, C1-C6 haloalkyl, or cycloalkyl; wherein in this case, each of alkyl and cycloalkyl is independently optionally substituted with one or more R 11ais optionally replaced. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 11 is C1-C6 alkyl, or cycloalkyl; in which case each of the alkyl and cycloalkyl is independently optionally substituted with one or more R 11a is optionally replaced. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 11 is C1-C6 alkyl, C1-C6 deuterated alkyl, C1-C6 haloalkyl, or cycloalkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 11 is C1-C6 alkyl, C1-C6 haloalkyl, or cyclo alkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 11 is C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 11 is C1-C6 alkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 11 is cycloalkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), R 11 is C1-C6 alkyl, C1-C6 deuterated alkyl, or cycloalkyl.

[0281] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), each R 11a is independently deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NRc R d 、 C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, C1-C6 hydroxyalkyl, or C1-C6 aminoalkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), each R 11a is independently deuterium , halogen, -CN, -OR b , -NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, C1-C6 hydroxyalkyl, or C1-C6 aminoalkyl. In some embodiments of the compounds of formula (XII) , (XII’), (XIIa), (XIIb), or (XIIc), each R 11a is independently deuterium, halogen, -CN, -OR b , -NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb ), or (XIIc), each R 11a is independently deuterium, halogen, -CN, -OR b , -NR c R d , or C1-C6 alkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), each R 11a is independently deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 deuterated alkyl . In some embodiments of the compounds of formula (XII), (XII’), (XIIa), (XIIb), or (XIIc), each R 11a is independently deuterium, halogen, or C1-C6 alkyl.

[0282] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is halogen, -CN, -OR 8 , -SR 8 , -S(=O)R 7 , -S(=O)2R 7 , -NO2, -NR 9 R 10 , -NHS(=O)2R 7 , -S(=O)2NR 9 R 10 , -C(=N-CN)R 7 ,-C(=O)R 7 , -OC(=N-CN)R 7 , -OC(=O)R 7 , -C(=N-CN)OR 8 , -C(=O)OR 8 , -OC(=N-CN)OR 8 , -OC(=O)OR 8 , -C(=N-CN)NR 9 R 10 , -C(=O)NR 9 R 10 , -OC(=N-CN)NR 9 R 10 , -OC(=O)NR 9 R 10 , -NR 8 C(=N-CN)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=N-CN)R 7 , -NR 8 , -NR 7 , -NR 8 C(=N-CN)OR 8 , -NR 8 , -C(=O)OR 8 , -NR 8 , -S(=O)(=NR 8 )R 7 , C1-C6 alkyl, C1-C6 halo alkyl, C1-C6 deuterated alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl , C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; in this case, each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), C1-C6 a ryl(aryl), or C1-C6 alkyl(heteroaryl) optionally substituted; in this case, each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or optionally substituted with C1-C6 haloalkyl;

[0283] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is halogen, -CN, -OR 8 , -NR 9 R 10 , -C(=O)R 7, -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 , -NR 7 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , -NR 8 , -NR 8 )R 7 , C1-C6 alkyl , C1-C6 haloalkyl, C1-C6 deuterated alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or optionally substituted with C1-C6 haloalkyl.

[0284] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is halogen, -CN, -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=N-CN)R 7 , -NR 8C(=O)OR 8 , -NR 8 S(=O)(=NR 8 )R 7 , C1-C6 alkyl, C1-C6 halo alkyl, C1-C6 deuterated alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl , heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d 、C1-C6 alkyl, or C1-C6 haloalkyl, optionally substituted thereby.

[0285] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is halogen, -CN, -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=N-CN)R 7 , -NR 8 C(=O)OR 8 , -NR 8 S(=O)(=NR 8 )R 7 , C 1- C6 alkyl, C 1- C6 halo alkyl, C 1- C6 deuterated alkyl, C 2- C6 alkenyl, C2- C6 alkynyl, cycloalkyl a heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- 6 alkyl, or C 1- 6 haloalkyl optionally substituted with it.

[0286] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=N-CN)R 7 , -NR 8 C(=O)R 7 , -NR 8 C(=O)OR 8 , -NR 8 S(=O)(=NR 8 )R 7 , a cycloalkyl, heterocyclic a lower alkyl, aryl or heteroaryl; wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)Ra , -C(=O)OR b , -C(=O)NR c R d is optionally substituted with C1-C6 alkyl or C1-C6 haloalkyl.

[0287] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is -OR 8 , -NR 9 R 10 , -C(=O)R 7 , -C(=O)OR 8 , -C(=O)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=N-CN)R 7 , -NR 8 C(=O)OR 8 , -NR 8 S(=O)(=NR 8 )R 7 and is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where each of cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d and is optionally substituted with C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R is -OR 5 is -NR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 , -NR 8 C(=N-CN)R 7, -NR 8 S(=O)(=NR 8 )R 7 、 or one or more deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d and is aryl optionally substituted with C1-C6 alkyl or C1-C6 haloalkyl.

[0288] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=N-CN)R 7 , -NR 8 S(=O)(=NR 8 )R 7 、 or one or more deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d and is aryl optionally substituted with C1-C6 alkyl or C1-C6 haloalkyl.

[0289] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is -OR 8 , -NR 9 R 10 , -NR 8 C(=O)R 7 and is cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b, -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d is optionally substituted with C1-C6 alkyl, or C1-C6 haloalkyl. Formula (XII), (XII’), (XIIa), or (XIIb) In some embodiments of the compounds of 5 R is one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, or C1-C6 halo aryl optionally substituted with alkyl.

[0290] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is -NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , or -NR 8 C(=N-CN)R 7 .

[0291] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is -NR 9 R 10 .

[0292] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is -NR 9 R 10 or -NR 8 C(=O)NR 9 R 10 .

[0293] In some embodiments of the compound of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is -NR 8 C(=N-CN)R 7 .

[0294] In some embodiments of the compound of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is -NR 8 S(=O)(=NR 8 )R 7 .

[0295] In some embodiments of the compound of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is -NR 8 C(=O)NR 9 R 10 or -NR 8 C(=O)R 7 .

[0296] In some embodiments of the compound of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is -NR 8 C(=O)NR 9 R 10 .

[0297] In some embodiments of the compound of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is -NR 8 C(=O)R 7 .

[0298] In some embodiments of the compound of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is -NR 8 C(=O)R 7 is not.

[0299] In some embodiments of the compound of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is -NR 8 C(=O)NR 9 R 10 , or one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deutero alkylated alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl , C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), C1-C6 alkyl(aryl), or C1-C6 alkyl(heteroaryl)-substituted heterocycloalkyl; wherein in each case alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl or C1-C6 haloalkyl-substituted .

[0300] In some embodiments of the compound of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a, -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, C1-C6 hydro xyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), C1-C6 alk yl(aryl), or C1-C6 alkyl(heteroaryl), optionally substituted with heterocy cloalkyl; wherein in each case alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are each independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , optionally substituted with C1-C6 alkyl or C1-C6 haloalkyl.

[0301] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl , C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, hete rocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(cycloalkyl), or heterocycloalkyl optionally substituted with C1-C6 alkyl(heterocycloalkyl) wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl or C1-C6 haloalkyl.

[0302] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5 is one or more oxo, halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deutero alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl yl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, C1-C6 alkyl(cycloalkyl), or heterocycloalkyl optionally substituted with C1-C6 alkyl(heterocycloalkyl); wherein each of alkyl, alkynyl, cycloalkyl, heterocycloalkyl, and aryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OR wherein each of alkyl, alkynyl, cycloalkyl, heterocycloalkyl, and aryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C1-C6 alkyl or C1-C6 haloalkyl.

[0303] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5The heterocycloalkyl is [Chemical formula] as follows.

[0304] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 5 The heterocycloalkyl is [Chemical formula] as follows.

[0305] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 7 is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, he terocycloalkyl, aryl or heteroaryl; wherein each of the alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 7 is C1-C6 alkyl, cycloalkyl, or heterocycloalkyl; wherein in this case, each of the alkyl, cycloalkyl, or heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (XII), (XII’ ), (XIIa), or (XIIb), R 7is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; in which case wherein each of the alkyl and cycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 7 is C1-C6 alkyl, or cycloalkyl wherein each of the alkyl and cycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe , C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 7 is cycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 7 is unsubstituted chloroalkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 7 is heterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl . In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 7 is unsubstituted heterocycloalkyl.

[0306] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 8 is hydrogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cyclo alkyl, heterocycloalkyl, aryl or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl is substituted. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 8 is hydrogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 halo alkyl.

[0307] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 9 and R 10is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, C1-C6 deuterated alkyl , C1-C6 haloalkyl, or C1-C6 hydroxyalkyl. In some embodiments of the compounds of formula (XII) , (XII’), (XIIa), or (XIIb), R 9 and R 10 are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, or cycloalkyl; wherein each of alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, C1-C6 deuterated alkyl, C1-C6 haloalkyl, or C1-C6 hydroxyalkyl.

[0308] In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 9 and R 10 together with the nitrogen atom to which they are attached form a heterocycloalkyl optionally substituted with one or more oxo, deuterium, halo gen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 9 and R 10Together with the nitrogen atom to which they are attached, one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl forms C2-C8 heterocycloalkyl optionally substituted with haloalkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R 9 and R 10 together with the nitrogen atom to which they are attached form bicyclic heterocycloalkyl or spiroheterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments of the compounds of formula (XII), (XII’), (XIIa), or (XIIb), R and R 9 and R 10 together with the nitrogen atom to which they are attached each form heterocycloalkyl selected from aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, 2-azabicyclo[1.1.1]pentanyl, or 2-azaspiro[3.3]heptanyl, each optionally substituted with one or more oxo, deuterium , halogen, -CN, -OH, -OMe, -NH2, -C(=O)Me, -C(=O)OH, -C(=O)OMe, C1-C6 alkyl, or C1-C6 haloalkyl.

[0309] In some embodiments of the compounds of formula (XII), the compound is a compound of formula (XIIc) below.

Chemical formula

[0310] In some embodiments of the compound of formula (XIIc), R 5a is deuterium, halogen, -CN, -OR b , -NR c R d , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkynyl, cycloalk yl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(cycloalk yl), C1-C6 alkyl(heterocycloalkyl), C1-C6 alkyl(aryl), or C1-C6 alkyl(heteroaryl); wherein alkyl, alkenyl, al Each of kinyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d and is optionally substituted with C1-C6 alkyl or C1-C6 haloalkyl.

[0311] In some embodiments of the compound of formula (XIIc), R 5a is halogen, -OR b , C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 deuterated alkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, C1-C6 alkyl(cycloalkyl), or C1-C6 alkyl(heterocycloalkyl); wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, and aryl is independently one or more oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d and is optionally substituted with C1-C6 alkyl or C1-C6 haloalkyl.

[0312] Disclosed herein are compounds of formula (XIII) below, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof:

Chemical formula

Claims

1. A compound of formula (XII) below, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof: A combination of: 【Chemistry 1】 During the ceremony: Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 16 is -C(=O)NR 1 R 2 , -C(=N-CN)NR 1 R 2 , -P(=O)R 1 R 2 , or -C(=O)R 11 and R 1 and R 2 are independently hydrogen, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated A Rukill, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, or C 2- C 6 alkynyl; R 3 is hydrogen, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, or C 1- C 6 Deuterated alkyl the law of nature; R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O) 2 R a , -NO 2 , -NR c R d , -NHS(=O) 2 R a , -S(=O) 2 NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , -P(=O)R b R b , C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, or C 2- C 6 alkynyl; or R 3 and R 4 together form an optionally substituted ring; L is a bond or -C(=O)-; Ring A is a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl. each of which has one or more R A optionally replaced by; Each R A are independently deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O) 2 R a , -NO 2 , -NR c R d , -NHS(=O) 2 R a , -S(=O) 2 NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C 6 Alkyl, or C 1- C 6 Optionally substituted with haloalkyl ； or two R on the same carbon A together form oxo; or -L-ring A is absent; Each X is independently -CR x -or -N-; Each R X are independently hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O) 2 R a , -NO 2 , -NR c R d , -NHS(=O) 2 R a , -S(=O) 2 NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, or C 2- C 6 alkynyl; R 5 is halogen, -CN, -OR 8 , -SR 8 , -S(=O)R 7 , -S(=O) 2 R 7 , -NO 2 , -NR 9 R 10 , -NR 8 S(=O)R 7 , -NR 8 S(=O) 2 R 7 , -S(=O) 2 NR 9 R 10 , -C(=N-CN)R 7 ,-C(=O)R 7 , -OC(=N-CN)R 7 , -OC(=O)R 7 , -C(=N-CN)OR 8 , -C(=O)OR 8 , -OC(=N-CN)OR 8 , -OC(=O)OR 8 , -C(=N-CN)NR 9 R 10 , -C(=O)NR 9 R 10 , -OC(=N-CN)NR 9 R 10 , -OC(=O)NR 9 R 10 , -NR 8 C(=N-CN)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=N-CN)R 7 , -NR 8 C(=N-OH)R 7 , -NR 8 C(=N-CN)OR 8 , -NR 8 C(=O)OR 8 , -NR 8 S(=O)(=NR 8 )R 7 , C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 1 -C 6 Heteroalkyl, C 2- C 6 Alkenyl, or C 2- C 6 Alkynyl, cycloalkyl, heterocycloalkyl, aryl Heteroaryl, C 1 -C 6 Alkyl (cycloalkyl), C 1 -C 6 Alkyl (heterocycloalkyl), C 1 -C 6 Alkyl (aryl), or C 1 -C 6 and optionally substituted with alkyl (heteroaryl); in which each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently is selected from one or more of oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C 6 Alkyl, or C 1- C 6 optionally substituted with haloalkyl; R 7 is C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 Alkynyl, cycloalkyl , heterocycloalkyl, aryl, or heteroaryl; in which each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 HelloA optionally substituted with rutile; Each R 8 are independently hydrogen, CN, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated Al Kill, C. 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 optionally substituted with haloalkyl; R 9 and R 10 are independently hydrogen, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 optionally substituted with hydroxydeuterated alkyl, cycloalkyl, or heterocycloalkyl; or R 9 and R 10 may be, together with the nitrogen atom to which they are attached, one or more oxo, Hydrogen, halogens, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 forming a heterocycloalkyl optionally substituted with haloalkyl; or R 8 and R 9 together with the atom to which they are attached, one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 forming a heterocycloalkyl optionally substituted with haloalkyl; R 11 is C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Deuterated alkyl, C 1 -C 6 Hydroxy Dialkyl, C 1 -C 6 Aminoalkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, cycloalkynyl alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; and heteroaryl, each independently being one or more R 11a optionally replaced by; Each R 11a are independently deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O) 2 R a , -NO 2 , -NR c R d , -NHS(=O) 2 R a , -S(=O) 2 NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, or C 2- C 6 alkynyl; Each R a is independent, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 Alkynyl, Cyclo wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 optionally substituted with haloalkyl; Each R b are independently hydrogen, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl , C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 optionally substituted with haloalkyl; Each R c and R d are independently hydrogen, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuteration Alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 optionally substituted with haloalkyl; or R c and R d together with the nitrogen atom to which they are attached, one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 Compounds forming heterocycloalkyl optionally substituted with haloalkyl. thing.

2. A compound according to claim 1, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof. It is a thing, A compound wherein Ring B is aryl or heteroaryl.

3. 3. A compound according to claim 1 or 2, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, L is a bond, the compound.

4. A compound according to any one of claims 1 to 3, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, Ring A is heterocycloalkyl or heteroaryl; each of which is one or more R A The compound optionally substituted with

5. A compound according to any one of claims 1 to 3, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, Ring A is a 5-membered heterocycloalkyl or a 5-membered heteroaryl; each of which is One or more R's A The compound optionally substituted with

6. A compound according to any one of claims 1 to 5, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, Each R A are independently deuterium, halogen, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, or C 1- C 6 A compound which is a deuterated alkyl.

7. A compound according to any one of claims 1 to 6, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, R 4 Hydrogen, deuterium, halogens, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, or C 1- C 6 A compound which is a deuterated alkyl.

8. A compound according to any one of claims 1 to 7, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, R 4 is hydrogen or -OR b A compound.

9. 9. The compound according to any one of claims 1 to 8, wherein the compound is of formula (XIIa): 【Chemistry 2】

10. A compound according to any one of claims 1 to 9, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, R 3 A compound in which is hydrogen.

11. A compound according to any one of claims 1 to 10, or a pharma- ceutically acceptable salt thereof, isomers or solvates thereof, R 16 But -C(=O)NR 1 R 2 A compound.

12. A compound according to any one of claims 1 to 11, or a pharma- ceutically acceptable salt thereof, isomers or solvates thereof, R 1 and R 2 are independently hydrogen, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, or C 1- C 6 heavy water A compound which is an alkyl hydride.

13. A compound according to any one of claims 1 to 12, or a pharma- ceutically acceptable salt thereof, isomers or solvates thereof, R 1 A compound in which is hydrogen.

14. A compound according to any one of claims 1 to 13, or a pharma- ceutically acceptable salt thereof, isomers or solvates thereof, R 2 But, C 1- C 6 Alkyl or C 1- C 6 A compound which is a deuterated alkyl.

15. A compound according to any one of claims 1 to 14, or a pharma- ceutically acceptable salt thereof, isomers or solvates thereof, R 2 But, C 1 -C 6 A compound which is a deuterated alkyl.

16. A compound according to any one of claims 1 to 10, or a pharma- ceutically acceptable salt thereof, isomers or solvates thereof, R 16 But -C(=O)R 11 A compound.

17. A compound according to any one of claims 1 to 10 or 16, or a pharma- ceutically acceptable salt thereof. a salt, stereoisomer or solvate thereof, R 11 But, C 1- C 6 Alkyl, C 1- C 6 A compound which is a haloalkyl, or a cycloalkyl.

18. A compound according to any one of claims 1 to 17, or a pharma- ceutically acceptable salt thereof, isomers or solvates thereof, 【Chemistry 3】 A compound.

19. A compound according to any one of claims 1 to 18, or a pharma- ceutically acceptable salt thereof, isomers or solvates thereof, R 5 But -NR 8 C(=O)NR 9 R 10 or one or more of oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Deuterated alkyl, C 1 -C 6 Hydroxyalkyl, C 1 -C 6 Aminoalkyl, C 1 -C 6 Heteroar Kill, C. 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 Alkyl (cycloalkyl), C 1 -C 6 Alkyl (heterocycloalkyl), C 1 -C 6 Alkyl (aryl), or C 1 -C 6 heterocycloalkyl optionally substituted with alkyl(heteroaryl); where alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl each independently represent one or more of oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1 -C 6 Alkyl or C 1 -C 6 Optionally substituted with haloalkyl A compound that can be used.

20. A compound according to any one of claims 1 to 19, or a pharma- ceutically acceptable salt thereof, isomers or solvates thereof, R 5 is one or more of oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Deuterated alkyl, C 1 -C 6 Hydroxyalkyl, C 1 -C 6 Aminoalkyl, C 1 -C 6 Heteroalkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 Alkyl (cycloalkyl), C 1 -C 6 Alkyl (heterocycloalkyl), C 1 -C 6 a Aryl, or C 1 -C 6 Heteroaryl optionally substituted with alkyl wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1 -C 6 Alkyl or C 1 -C 6 A compound optionally substituted with haloalkyl.

21. A compound according to any one of claims 1 to 19, or a pharma- ceutically acceptable salt thereof, isomers or solvates thereof, R 5 But -NR 8 C(=O)NR 9 R 10 A compound.

22. A compound according to any one of claims 1 to 21, or a pharma- ceutically acceptable salt thereof, isomers or solvates thereof, R 9 and R 10 together with the nitrogen atom to which they are attached, one or more oxo, deuterium, Halogens: -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 Compounds that form heterocycloalkyl optionally substituted with haloalkyl.

23. 1. A compound of formula (XIII) or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof: 【Chemistry 4】 During the ceremony: Ring B is a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl. can be; R 3 is hydrogen, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, or C 1- C 6 Deuterated alkyl the law of nature; R 4 is hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O) 2 R a , -NO 2 , -NR c R d , -NHS(=O) 2 R a , -S(=O) 2 NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , -P(=O)R b R b , C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, or C 2- C 6 alkynyl; or R 3 and R 4 together form an optionally substituted ring; L is a bond or -C(=O)-; Ring A is a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl. each of which has one or more R A optionally replaced by; Each R A are independently deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O) 2 R a , -NO 2 , -NR c R d , -NHS(=O) 2 R a , -S(=O) 2 NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C 6 Alkyl, or C 1- C 6 Optionally substituted with haloalkyl ； or two R on the same carbon A together form oxo; or -L-ring A is absent; Each X is independently -CR x -or -N-; Each R X are independently hydrogen, deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O) 2 R a , -NO 2 , -NR c R d , -NHS(=O) 2 R a , -S(=O) 2 NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C 6 Alkyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Deuterated alkyl, C 1 -C 6 Hydroxyalkyl, C 1 -C 6 Aminoalkyl, C 2 -C 6 Alkenyl, or C 2 -C 6 alkynyl; R 5 は、ハロゲン、-CN, -OR 8 , -SR 8 , -S(=O)R 7 , -S(=O) 2 R 7 , -NO 2 , -NR 9 R 10 , -NR 8 S(=O)R 7 , -NR 8 S(=O) 2 R 7 , -S(=O) 2 NR 9 R 10 , -C(=N-CN)R 7 ,-C(=O)R 7 , -OC(=N-CN)R 7 , -OC(=O)R 7 , -C(=N-CN)OR 8 , -C(=O)OR 8 , -OC(=N-CN)OR 8 , -OC(=O)OR 8 , -C(=N-CN)NR 9 R 10 , -C(=O)NR 9 R 10 , -OC(=N-CN)NR 9 R 10 , -OC(=O)NR 9 R 10 , -NR 8 C(=N-CN)NR 9 R 10 , -NR 8 C(=O)NR 9 R 10 , -NR 8 C(=N-CN)R 7 , -NR 8 C(=N-OH)R 7 , -NR 8 C(=O)R 7 , -NR 8 C(=N-CN)OR 8 , -NR 8 C(=O)OR 8 , -NR 8 S(=O)(=NR 8 )R 7 , C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 Alkynyl, cycloalkyl , heterocycloalkyl, aryl, or heteroaryl; in which each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C 6 Alkyl, C 1- C 6 Haloalkyl , C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 1- C 6 Heteroalkyl, C 2- C 6 Alkenyl, C 2- C 6 Alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1- C 6 Alkyl (cycloalkyl), C 1- C 6 Alkyl (heterocycloalkyl), C 1- C 6 Alkyl (aryl), or C 1- C 6 and optionally substituted with alkyl (heteroaryl); in which each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently is selected from one or more of oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1- C 6 Alkyl, or C 1- C 6 optionally substituted with haloalkyl; R 7 is C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 Alkynyl, cycloalkyl , heterocycloalkyl, aryl, or heteroaryl; in which each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 HelloA optionally substituted with rutile; Each R 8 are independently hydrogen, CN, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated Al Kill, C. 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 optionally substituted with haloalkyl; R 9 and R 10 are independently hydrogen, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 optionally substituted with hydroxydeuterated alkyl, cycloalkyl, or heterocycloalkyl; or R 9 and R 10 may be, together with the nitrogen atom to which they are attached, one or more oxo, Hydrogen, halogens, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 forming a heterocycloalkyl optionally substituted with haloalkyl; or R 8 and R 9 together with the atom to which they are attached, one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 forming a heterocycloalkyl optionally substituted with haloalkyl; R 11 is C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Deuterated alkyl, C 1 -C 6 Hydroxy Dialkyl, C 1 -C 6 Aminoalkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, cycloalkynyl wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently selected from one or more R 11a optionally replaced by; Each R 11a are independently deuterium, halogen, -CN, -OR b , -SR b , -S(=O)R a , -S(=O) 2 R a , -NO 2 , -NR c R d , -NHS(=O) 2 R a , -S(=O) 2 NR c R d , -C(=O)R a , -OC(=O)R a , -C(=O)OR b , -OC(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , -NR b C(=O)NR c R d , -NR b C(=O)R a , -NR b C(=O)OR b , C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, or C 2- C 6 alkynyl; Each R a is independent, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 Alkynyl, Cyclo wherein each of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 optionally substituted with haloalkyl; Each R b are independently hydrogen, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuterated alkyl , C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 optionally substituted with haloalkyl; Each R c and R d are independently hydrogen, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, C 1- C 6 Deuteration Alkyl, C 1- C 6 Hydroxyalkyl, C 1- C 6 Aminoalkyl, C 2- C 6 Alkenyl, C 2- C 6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 optionally substituted with haloalkyl; or R c and R d together with the nitrogen atom to which they are attached, one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 Compounds forming heterocycloalkyl optionally substituted with haloalkyl. thing.

24. 24. A compound according to claim 23, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, A compound wherein Ring B is aryl or heteroaryl.

25. 25. A compound according to claim 23 or 24, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, L is a bond, the compound.

26. A compound according to any one of claims 23 to 25, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, Ring A is one or more R A The compound wherein R is a 5-membered heteroaryl optionally substituted with

27. A compound according to any one of claims 23 to 26, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, Each R A are independently deuterium, halogen, C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, or C 1- C 6 A compound which is a deuterated alkyl.

28. A compound according to any one of claims 23 to 27, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, R 4 Hydrogen, deuterium, halogens, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , -OC(=O)NR c R d , C 1- C 6 Alkyl, C 1- C 6 Haloalkyl, or C 1- C 6 A compound which is a deuterated alkyl.

29. A compound according to any one of claims 23 to 28, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, R 4 is hydrogen or -OR b A compound.

30. A compound according to any one of claims 23 to 29, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, R 3 A compound in which is hydrogen.

31. A compound according to any one of claims 23 to 30, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, R 11 But, C 1- C 6 Alkyl, C 1- C 6 Deuterated alkyl, C 1- C 6 A compound which is a haloalkyl, or a cycloalkyl.

32. A compound according to any one of claims 23 to 31, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, 【Chemistry 5】 A compound.

33. A compound according to any one of claims 23 to 32, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, R 5 But -NR 8 C(=O)R 7 , -NR 8 C(=O)NR 9 R 10 or one or more of oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1 -C 6 Alkyl, C 1 -C 6 HelloA Rukill, C 1 -C 6 Deuterated alkyl, C 1 -C 6 Hydroxyalkyl, C 1 -C 6 Aminoalkyl, C 1 -C 6 Heteroalkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 Alkyl (cycloalkyl), C 1 -C 6 Alkyl (heterocycloalkyl), C 1 -C 6 Alkyl (aryl), or C 1 -C 6 heterocycloalkyl optionally substituted with alkyl(heteroaryl); where alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl each independently represent one or more of oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1 -C 6 Alkyl, or C 1 -C 6 Hello Aruki The compound is optionally substituted with

34. A compound according to any one of claims 23 to 33, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, R 5 is one or more of oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1 -C 6 Alkyl, C 1 -C 6 Haloalkyl, C 1 -C 6 Deuterated alkyl, C 1 -C 6 Hydroxyalkyl, C 1 -C 6 Aminoalkyl, C 1 -C 6 Heteroalkyl, C 2 -C 6 Alkenyl, C 2 -C 6 Alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C 1 -C 6 Alkyl (cycloalkyl), C 1 -C 6 Alkyl (heterocycloalkyl), C 1 -C 6 a Aryl, or C 1 -C 6 Heteroaryl optionally substituted with alkyl wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently represents one or more of oxo, deuterium, halogen, -CN, -OR b , -NR c R d , -C(=O)R a , -C(=O)OR b , -C(=O)NR c R d , C 1 -C 6 Alkyl or C 1 -C 6 A compound optionally substituted with haloalkyl.

35. A compound according to any one of claims 23 to 32, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, R 5 But -NR 8 C(=O)NR 9 R 10 A compound.

36. A compound according to any one of claims 23 to 35, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, R 9 and R 10 together with the nitrogen atom to which they are attached, one or more oxo, deuterium, Halogens: -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1- C 6 Alkyl, or C 1- C 6 Compounds that form heterocycloalkyl optionally substituted with haloalkyl.

37. A compound according to any one of claims 23 to 32, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, R 5 But -NR 8 C(=O)R 7 A compound.

38. A compound according to any one of claims 23 to 32 or 37, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof, R 7 but one or more of oxo, deuterium, halogen, -CN, -OH, -OMe, -NH 2 , -C(=O)Me, -C(=O)OH, -C(=O)OMe, C 1 -C 6 Alkyl, or C 1 -C 6 Cyclo optionally substituted with haloalkyl A compound which is an alkyl.

39. A compound selected from the following, or a pharma- ceutically acceptable salt, stereoisomer, or solvate thereof: 【Chemistry 6-1】 【Chemistry 6-2】 【Chemistry 6-3】 【Chemistry 6-4】 【Chemistry 6-5】 【Chemistry 6-6】 【Chemistry 6-7】 【Chemistry 6-8】 【Chemistry 6-9】 【Chemistry 6-10】 【Chemistry 6-11】 【Chemistry 6-12】 【Chemistry 6-13】

40. A compound selected from the following, or a pharma- ceutically acceptable salt, stereoisomer, or solvate thereof: 【Chemistry 7-1】 【Chemistry 7-2】 【Chemistry 7-3】 【Chemistry 7-4】 【Chemistry 7-5】 【Chemistry 7-6】 【Chemistry 7-7】 【Chemistry 7-8】 【Chemistry 7-9】 【Chemistry 7-10】

41. A compound according to any one of claims 1 to 40 or a pharma- ceutically acceptable salt thereof, A pharmaceutical composition comprising a therapeutically effective amount of a solvate of the compound, and a pharma- ceutically acceptable excipient.

42. A method for inhibiting the TYK2 enzyme in a patient or biological sample, comprising administering to said patient or biological sample a compound according to any one of claims 1 to 40 or a pharmaceutical formulation thereof. A method comprising contacting a compound comprising the steps of:

43. A method for treating a TYK2-mediated disorder, comprising administering to a patient in need thereof any one of claims 1 to 40.

20. A method comprising administering a compound according to any one of claims 1 to 9, or a pharma- ceutically acceptable salt, stereoisomer or solvate thereof.

44. 44. The method of claim 43, wherein the TYK2-mediated disorder is an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a transplant-related disorder.

45. 44. The method of claim 43, wherein the disorder is associated with type I interferon, IL-10, IL-12, or IL-23 signaling.

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