Lysine acetyltransferase 6A (KAT6A) inhibitors, combinations and uses thereof

Abstract

Described herein are methods of treating cancer using small molecule lysine acetyltransferase 6a (KAT6A) inhibitors and additional agents.

Description

CROSS-REFERENCE

[0001] This patent application claims the benefit of International Application No. PCT / CN2023 / 089277, filed April 19, 2023, and International Application No. PCT / CN2024 / 086020, filed April 3, 2024; and said International Applications are incorporated herein by reference in their entirety. BACKGROUND

[0002] Lysine acetyltransferase 6A (KAT6A) belongs to the MYST family of acetyltransferases and was first discovered about 25 years ago. KAT6A controls fundamental cellular processes, including gene transcription, cellular senescence, heart septum development, memory T cell diversity, and maintenance of normal hematopoietic stem cells. Dysregulation of KAT6A acetyltransferase activity or abnormal expression of KAT6A has been associated with oncogenic functions in a variety of cancers, including leukemia, glioma, endometrial serous carcinoma, and breast cancer. Therefore, compounds that inhibit KAT6A are potential agents for treating a variety of cancers.

[0003] First-line treatment with cyclin-dependent kinase 4 and 6 inhibitors (CDK4 / 6i) and endocrine therapy (ET) has improved long-term outcomes for patients with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced or metastatic breast cancer. Following CDK4 / 6i and ET, oncologists typically treat patients with sequential ET-based regimens for as long as possible because these regimens have generally lower toxicity than chemotherapy. Disadvantageously, acquired tumors that are resistant to ET are common.

[0004] Molecular dysregulation of KAT6A has been observed in several cancers, including amplification in breast, lung, and ovarian cancer and oncogenic fusions in AML. In breast cancer, KAT6A is thought to be amplified and / or overexpressed in 10-15% of the ER-positive breast cancer population. KAT6A is a direct transcriptional regulator of ESR1 and amplification is associated with worse clinical outcomes. First- and second-line treatment options for HR-positive / HER2-negative breast cancer include endocrine therapy, CDK4 / 6 inhibitors, and targeted therapies. Patients with refractory disease have few treatment options. Therefore, KAT6A is considered a clinically meaningful therapeutic target for ER-positive / HER2-negative breast cancer. SUMMARY

[0005] In one aspect, provided herein is a method of treating cancer in a subject in need thereof, the method comprising administering to the subject: (a) a compound of Formula (I) or a pharmaceutically acceptable salt thereof: ; wherein: Y 1 is CR 1a or N; Y 2 is CR 2a or N; Y 3 is CR 3a or N; Y 4 is CR 4a or N; Y 5 is CR 5a or N; Z 1 is CR 1b or N; Z 2 is CR 2b or N; Z 3 is CR 3b or N; wherein at least one of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Z 1 , Z 2 and Z 3 is N; X is selected from -C(R 6 )(R 6a )-, -O- and -N(R 7 )-; R 1 is C 1-9 heteroaryl, optionally substituted with one, two or three groups selected from R 15a ; R 1a , R 2a , R 3a , R 4a , R 5a , R 1b , R 2b and R 3b are independently selected from hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, C 1-9 heteroaryl, -OR 10 , -SR 10 , -SF5, -N(R10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two or three of R... 15b Substitution of groups; R 6 and R 6a Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; R 7 Selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 10 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 11 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R12 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 13 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl; and Each R 15a and each R 15b Each is independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -CH2-C 3-10 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 heteroaryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ); (b) Additional medications, The compound of formula (Ⅰ) or a combination of its pharmaceutically acceptable salt and additional agents is therapeutically effective for treating the cancer.

[0006] In another respect, this paper provides a method for treating cancer in a subject in need, the method comprising administering to the subject: (a) 2,4-Dimethoxy-N-(4-methoxy-6-(thiazolyl-2-yloxy)benzo[d]isoxazol-3-yl)-6-methylpyridine-3-sulfonamide (Compound 57), or a pharmaceutically acceptable salt thereof; and (b) Additional medications.

[0007] In another respect, this paper provides a method for treating cancer in a subject in need, the method comprising administering to the subject: (a) 2,4-Dimethoxy-N-(4-methoxy-6-(thiazolyl-2-yloxy)benzo[d]isoxazol-3-yl)-6-methylpyridine-3-sulfonamide (Compound 57), or a pharmaceutically acceptable salt thereof; and (b) Elacestrant.

[0008] In another aspect, this document provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating cancer, wherein the medicament is formulated for administration in combination with additional medicaments.

[0009] In another respect, this document provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof and additional agents in the manufacture of a medicament for treating cancer.

[0010] In another respect, this article provides the use of compound 57 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating cancer, wherein the medicament is formulated for use in combination with additional medicaments.

[0011] In another respect, this article provides the use of compound 57 or a pharmaceutically acceptable salt thereof and additional agents in the manufacture of a medicament for treating cancer. Attached Figure Description

[0012] The features of the invention are specifically set forth in the appended claims. A better understanding of the features of the invention will be obtained by referring to the following detailed description and accompanying drawings, which illustrate illustrative embodiments utilizing the principles of the invention, in which: Figure 1 This demonstrates changes in tumor volume in a PDX model treated with mediators and compounds disclosed herein.

[0013] Figure 2 The relative changes in body weight are shown in PDX models treated with media and compounds disclosed herein.

[0014] Figure 3A Demonstrating the use of compound 57, elastosin, or compound 57 + elastosin in IC 10 / ⅠC 25 / ⅠC 50 / ⅠC 75 Post-treatment based on breast cancer ER+ / KAT6a 高 ZR-75-1 cells as a control treatment standardized percentage of viable cells.

[0015] Figure 3B Compound 57 is shown alone or in combination with the ileus group (IC). 25 The dose-response curve of the combination of 56 nM.

[0016] Figure 4 Demonstration of breast cancer ER+ / KAT6a 高 Statistical analysis of cytotoxicity data obtained from the ZR-75-1 cell line.

[0017] Figure 5The Combenefit Combination Index plot shows the relationship between CI and the combined drug effect score (Fa) (dead cell score).

[0018] Figure 6 Showing ER+ / KAT6a 高 Compusyn table of the synergistic effect between compound 57 and ellastatin in the breast cancer ZR-75-1 cell line, which was evaluated using the Loewe algorithm via Combenefit software. Detailed Implementation

[0019] definition In the following description, certain specific details are set forth to provide a thorough understanding of the various embodiments. However, those skilled in the art will understand that this disclosure may be practiced without using these details. In other instances, well-known structures have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments. Unless the context otherwise requires, throughout this specification and in the subsequent claims, the word “comprise” and its variations (such as “comprises” and “comprising”) shall be regarded as having an open-ended inclusive meaning, that is, “including but not limited to”. Furthermore, the headings provided herein are for convenience only and do not constitute an explanation of the scope or meaning of the claimed invention.

[0020] Throughout this specification, references to "some embodiments" or "an embodiment" mean that a particular feature, structure, or characteristic described in connection with an embodiment is included in at least one embodiment. Therefore, the phrase "in one embodiment" or "in one embodiment" appearing throughout this specification does not necessarily refer to the same embodiment. Furthermore, a particular feature, structure, or characteristic may be combined in any suitable manner in one or more embodiments. Moreover, unless the context clearly indicates otherwise, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include the plural references. It should also be noted that unless the context clearly indicates otherwise, the term "or" is generally used to include the meaning of "and / or."

[0021] Unless otherwise indicated, the following terms shall have the following meanings as used herein: "Oxytochemical" refers to the compound oxygen (O).

[0022] The "carboxyl group" refers to -COOH.

[0023] "Cyano" refers to -CN.

[0024] "alkyl" refers to a straight-chain or branched monovalent hydrocarbon group having one to ten carbon atoms, more preferably one to six 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, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, and hexyl, as well as longer alkyl groups such as heptyl, octyl, and similar groups. Whenever it appears herein, numerical ranges such as "C1-C6 alkyl" or "C1-6 alkyl" mean that an alkyl group can consist of 1, 2, 3, 4, 5, or 6 carbon atoms, but the definition of this invention also covers the presence of the term "alkyl" where no numerical range is specified. In some embodiments, the alkyl group is C1-C6. 1-10 Alkyl group. In some embodiments, the alkyl group is C10. 1-6 Alkyl group. In some embodiments, the alkyl group is C10. 1-5 Alkyl group. In some embodiments, the alkyl group is C10. 1-4 Alkyl group. In some embodiments, the alkyl group is C10. 1-3 Alkyl groups. Unless otherwise specifically stated in this specification, alkyl groups may optionally be substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylic acid ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and similar groups. In some embodiments, the alkyl group is optionally substituted with oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkyl group is optionally substituted with halogen, -CN, -OH, or -OMe. In some embodiments, the alkyl group is optionally substituted with halogen.

[0025] "Alkenyl" refers to a straight-chain or branched hydrocarbon monovalent group having one or more carbon-carbon double bonds and having two to about ten carbon atoms, more preferably two to about six carbon atoms. The group may be arranged around the double bond in a manner that is not explicitly defined. Cis or TransConfiguration, and should be understood to include two isomers. Examples include, but are not limited to, vinyl (-CH=CH2), 1-propenyl (-CH2CH=CH2), isopropenyl [-C(CH3)=CH2], butenyl, 1,3-butadienyl, and similar groups. Whenever it appears herein, numerical ranges such as “C2-C6 alkenyl” or “C2-6 alkenyl” mean that the alkenyl group can consist of 2, 3, 4, 5, or 6 carbon atoms, although the definition of this invention also covers the presence of the term “alkenyl” without a specified numerical range. Unless otherwise specifically stated in this specification, the alkenyl group may optionally be substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and similar groups. In some embodiments, the alkenyl group is optionally substituted with an oxo group, a halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkenyl group is optionally substituted with a halogen, -CN, -OH, or -OMe. In some embodiments, the alkenyl group is optionally substituted with a halogen.

[0026] "Alynyl" refers to a straight-chain or branched hydrocarbon monovalent group having one or more carbon-carbon triple bonds and having two to about ten carbon atoms, more preferably two to about six carbon atoms. Examples include, but are not limited to, ethynyl, 2-propynyl, 2-butynyl, 1,3-butadiynyl, and similar groups. Whenever it appears herein, numerical ranges such as "C2-C6 alkynyl" or "C2-6 alkynyl" mean that the alkynyl group can consist of 2, 3, 4, 5, or 6 carbon atoms, but the definition of this invention also covers the presence of the term "alkynyl" without a specified numerical range. Unless otherwise specifically stated in this specification, the alkynyl group may optionally be substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxyl ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and similar groups. In some embodiments, the alkynyl group is optionally substituted with an oxo group, a halogen group, -CN, -COOH, COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkynyl group is optionally substituted with a halogen group, -CN, -OH, or -OMe. In some embodiments, the alkynyl group is optionally substituted with a halogen group.

[0027] "alkylene" refers to a straight-chain or branched divalent hydrocarbon chain. Unless otherwise specifically stated in this specification, alkylene may optionally be substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxyl ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and similar groups. In some embodiments, alkylene is optionally substituted with oxo, halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, alkylene is optionally substituted with halogen, -CN, -OH, or -OMe. In some embodiments, alkylene is optionally substituted with halogen.

[0028] "Alkoxy" refers to the formula -OR a The group, wherein R a The alkyl group is defined as such. Unless otherwise specifically stated in this specification, the alkoxy group may optionally be substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylic acid ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and similar groups. In some embodiments, the alkoxy group is optionally substituted with a halogen, -CN, -COOH, COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkoxy group is optionally substituted with a halogen, -CN, -OH, or -OMe. In some embodiments, the alkoxy group is optionally substituted with a halogen.

[0029] "Aryl" refers to a group derived from a hydrocarbon ring system containing 6 to 30 carbon atoms and at least one aromatic ring. Aryl groups can be monocyclic, bicyclic, tricyclic, or tetracyclic ring systems, and can include fused (when fused with a cycloalkyl or heterocyclic alkyl ring, the aryl group is bonded through aromatic ring atoms) or bridged ring systems. In some embodiments, the aryl group is a 6- to 10-membered aryl group. In some embodiments, the aryl group is a 6-membered aryl (phenyl). Aryl groups include, but are not limited to, aryl groups derived from the following hydrocarbon ring systems: anthracene, naphthyl, phenanthrene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, as-indacene, s-indacene, indene, indene, naphthalene, phenanthrene, pleiadene, pyrene, and benzo[a]phenanthrene. Unless otherwise specifically stated in this specification, the aryl group may optionally be substituted with, for example, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylic acid ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and similar groups. In some embodiments, the aryl group is optionally substituted with halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the aryl group is optionally substituted with halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the aryl group is optionally substituted with halogen.

[0030] "Cycloalkyl" refers to a partially or fully saturated monocyclic or polycyclic carbon ring, which may include fused (when fused with an aryl or heteroaryl ring, the cycloalkyl group is bonded by non-aromatic ring atoms), helical, or bridged ring systems. In some embodiments, the cycloalkyl group is fully saturated. Representative cycloalkyl groups include, but are not limited to, those having three to fifteen carbon atoms (C3-C5). 15 Fully saturated cycloalkyl or C3-C 15 Cycloalkenyl), three to ten carbon atoms (C3-C) 10 Fully saturated cycloalkyl or C3-C 10 Cycloalkyl groups are 3- to 10-membered fully saturated cycloalkyl groups or 3- to 10-membered cycloalkenyl groups. In some embodiments, the cycloalkyl group is 3- to 6-membered fully saturated cycloalkyl groups or 3- to 6-membered cycloalkenyl groups. In some embodiments, the cycloalkyl group is 5- to 6-membered fully saturated cycloalkyl groups or 5- to 6-membered cycloalkenyl groups. Monocyclic cycloalkyl groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyl groups include, for example, adamantyl, norbornel, decahydronaphthyl, bicyclo[3.3.0]octane, bicyclo[4.3.0]nonane, cis-decahydronaphthyl, trans-decahydronaphthyl, 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]heptyl. Partially saturated cycloalkyl groups include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless otherwise specifically stated in this specification, cycloalkyl groups are optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxyl ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and similar groups. In some embodiments, the cycloalkyl group is optionally substituted with an oxo, halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the cycloalkyl group is optionally substituted with an oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the cycloalkyl group is optionally substituted with a halogen.

[0031] "Halogen" or "halogen" refers to bromine, chlorine, fluorine, or iodine. In some embodiments, the halogen is fluorine or chlorine.

[0032] "Halogenated alkyl" refers to an alkyl group as defined above, which is substituted with one or more halogen groups as defined above, such as trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl and similar groups.

[0033] "Hydroxyalkyl" refers to an alkyl group as defined above that is substituted with one or more hydroxyl groups. In some embodiments, the alkyl group is substituted with one hydroxyl group. In some embodiments, the alkyl group is substituted with one, two, or three hydroxyl groups. Hydroxyalkyl groups include, for example, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, or hydroxypentyl. In some embodiments, the hydroxyalkyl group is hydroxymethyl.

[0034] "Aminoalkyl" refers to an alkyl group as defined above that is substituted with one or more amines. In some embodiments, the alkyl group is substituted with one amine. In some embodiments, the alkyl group is substituted with one, two, or three amines. Aminoalkyl groups include, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the aminoalkyl group is aminomethyl.

[0035] "Heteroalkyl" means an alkyl group in which one or more skeletal atoms are selected from atoms other than carbon, such as oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, phosphorus, or combinations thereof. The heteroalkyl group is attached to the remainder of the molecule at the carbon atom of the heteroalkyl group. In one aspect, the heteroalkyl group is a C1-C6 heteroalkyl group, wherein the heteroalkyl group comprises 1 to 6 carbon atoms and one or more atoms other than carbon, such as oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, phosphorus, or combinations thereof, wherein the heteroalkyl group is attached to the remainder of the molecule at the carbon atom of the heteroalkyl group. Examples of such heteroalkyl groups are, for example, -CH2OCH3, -CH2CH2OCH3, -CH2CH2OCH2CH2OCH3, -CH(CH3)OCH3, -CH2NHCH3, -CH2N(CH3)2, -CH2CH2NHCH3, or -CH2CH2N(CH3)2. Unless otherwise specifically stated in this specification, heteroalkyl groups are optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and similar groups. In some embodiments, heteroalkyl groups are optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, heteroalkyl groups are optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, heteroalkyl groups are optionally substituted with halogens.

[0036] "Heterocyclic alkyl" refers to a 3- to 24-membered partially or fully saturated cyclic group comprising 2 to 23 carbon atoms and 1 to 8 heteroatoms selected from nitrogen, oxygen, phosphorus, silicon, and sulfur. In some embodiments, the heterocyclic alkyl is fully saturated. In some embodiments, the heterocyclic alkyl comprises one to three heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the heterocyclic alkyl comprises one to three heteroatoms selected from nitrogen and oxygen. In some embodiments, the heterocyclic alkyl comprises one to three nitrogen atoms. In some embodiments, the heterocyclic alkyl comprises one or two nitrogen atoms. In some embodiments, the heterocyclic alkyl comprises one nitrogen atom. In some embodiments, the heterocyclic alkyl comprises one nitrogen atom and one oxygen atom. Unless otherwise specifically stated in this specification, the heterocyclic alkyl may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with an aryl or heteroaryl ring, the heterocyclic alkyl is bonded by non-aromatic ring atoms), helicaled, or bridged ring systems; and the nitrogen, carbon, or sulfur atoms in the heterocyclic alkyl may optionally be oxidized; the nitrogen atom may optionally be quaternized. Representative heterocyclic alkyl groups include, but are not limited to, those having two to fifteen carbon atoms (C2-C4). 15 Fully saturated heterocyclic alkyl or C2-C 15 Heterocyclic alkenyl groups, two to ten carbon atoms (C2-C) 10 Fully saturated heterocyclic alkyl or C2-C 10Heterocyclic alkyl groups consisting of two to eight carbon atoms (C2-C8 fully saturated heterocyclic alkyl or C2-C8 heterocyclic alkyl), two to seven carbon atoms (C2-C7 fully saturated heterocyclic alkyl or C2-C7 heterocyclic alkyl), two to six carbon atoms (C2-C6 fully saturated heterocyclic alkyl or C2-C7 heterocyclic alkyl), two to five carbon atoms (C2-C5 fully saturated heterocyclic alkyl or C2-C5 heterocyclic alkyl), or two to four carbon atoms (C2-C4 fully saturated heterocyclic alkyl or C2-C4 heterocyclic alkyl). Examples of such heterocyclic alkyl groups include, but are not limited to, azirropropyl, azirrobutyl, oxacyclobutyl, dioxopentyl, thienyl[1,3]dithiaalkyl, decahydroisoquinolinyl, imidazolinyl, imidazoalkyl, isothiazolyl, isoxazolyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperidinyl, 2-oxopiperidinyl, 2-oxopiperidinyl, 2-oxopiperidyl, oxazolyl, piperidinyl, piperazine, 4-piperidinoneyl, pyrrolyl, pyrazolyl, quininecycloyl, thiazoalkyl. Tetrahydrofuranyl, trithiaalkyl, 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-dioxacyclopenten-4-yl, and 2-oxo-1,3-dioxacyclopenten-4-yl. The term heterocyclic alkyl also includes all cyclic forms of carbohydrates, including but not limited to monosaccharides, disaccharides, and oligosaccharides. In some embodiments, the heterocyclic alkyl has 2 to 10 carbon atoms in the ring. It should be understood that when referring to the number of carbon atoms in a heterocyclic alkyl group, the number of carbon atoms in the heterocyclic alkyl group is not the same as the total number of atoms constituting the heterocyclic alkyl group (i.e., the skeletal atoms of the heterocyclic alkyl ring, including heteroatoms). In some embodiments, the heterocyclic alkyl group is a 3- to 8-membered fully saturated heterocyclic alkyl group. In some embodiments, the heterocyclic alkyl group is a 3- to 7-membered fully saturated heterocyclic alkyl group. In some embodiments, the heterocyclic alkyl group is a 3- to 6-membered fully saturated heterocyclic alkyl group. In some embodiments, the heterocyclic alkyl group is a 4- to 6-membered fully saturated heterocyclic alkyl group. In some embodiments, the heterocyclic alkyl group is a 5- to 6-membered fully saturated heterocyclic alkyl group. In some embodiments, the heterocyclic alkyl group is a 3- to 8-membered heterocyclic alkenyl group. In some embodiments, the heterocyclic alkyl group is a 3- to 7-membered heterocyclic alkenyl group. In some embodiments, the heterocyclic alkyl group is a 3- to 6-membered heterocyclic alkenyl group. In some embodiments, the heterocyclic alkyl group is a 4- to 6-membered heterocyclic alkenyl group. In some embodiments, the heterocyclic alkyl group is a 5- to 6-membered heterocyclic alkenyl group. Unless otherwise specifically stated in this specification, heterocyclic alkyl groups may optionally be substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylic acid ester, aryl, cycloalkyl, heterocyclic alkyl, heteroaryl and similar groups as described below.In some embodiments, the heterocyclic alkyl group is optionally substituted with an oxo, halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the heterocyclic alkyl group is optionally substituted with a halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heterocyclic alkyl group is optionally substituted with a halogen.

[0037] "Heteroaryl" refers to a 5- to 14-membered ring system group comprising one to thirteen carbon atoms, one to six heteroatoms selected from nitrogen, oxygen, phosphorus, and sulfur, and at least one aromatic ring. In some embodiments, the heteroaryl comprises one to three heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the heteroaryl comprises one to three heteroatoms selected from nitrogen and oxygen. In some embodiments, the heteroaryl comprises one to three nitrogen atoms. In some embodiments, the heteroaryl comprises one or two nitrogen atoms. In some embodiments, the heteroaryl comprises one nitrogen atom. The heteroaryl can be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocyclic alkyl ring, the heteroaryl is bonded through aromatic ring atoms) or bridged ring systems; and the nitrogen, carbon, or sulfur atom in the heteroaryl may optionally be oxidized; the nitrogen atom may optionally be quaternized. In some embodiments, the heteroaryl is a 5- to 10-membered heteroaryl. In some embodiments, the heteroaryl is a 5- to 6-membered heteroaryl. In some embodiments, the heteroaryl group is a 6-membered heteroaryl group. In some embodiments, the heteroaryl group is a 5-membered heteroaryl group. Examples include, but are not limited to, azatriyl, acridine, benzimidazolyl, benzothiazolyl, benzoindolyl, benzodioxolyl, benzofuranyl, benzooxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxyl, benzonaphthuryl, benzooxazolyl, benzo[m]dioxolyl, benzodioxinyl, benzopyranyl, benzopyranoneyl, benzofuranyl, benzofuranoneyl, benzothiopheneyl (benzophenylthio), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridyl, carbazole, cenyl, dibenzofuranyl, dibenzobenzene Thioyl, furanyl, furanoneyl, isothiazolyl, imidazolyl, indazole, indoleyl, indazole, isoindoleyl, indolinyl, isoindolinyl, isoquinolinyl, inazinyl, isoxazolyl, naphthidyl, oxadiazolyl, 2-oxoazapyridine, oxazolyl, ethylene oxide, 1-oxo-pyridyl, 1-oxo-pyrimidinyl, 1-oxo-pyrazinyl, 1-oxo-pyridazine The heteroaryl group can be substituted with, for example, 1-phenyl-1H-pyrroleyl, phenazinyl, phenothiazinyl, phenotoxazinyl, phthalazinyl, pteridinyl, purineyl, pyrroleyl, pyrazolyl, pyridinyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quininecycloyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e., thienyl). Unless otherwise specifically stated in this specification, the heteroaryl group may optionally be substituted with, for example, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylic ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and similar groups.In some embodiments, the heteroaryl group is optionally substituted with a halogen, methyl, ethyl, -CN, -COOH, COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the heteroaryl group is optionally substituted with a halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heteroaryl group is optionally substituted with a halogen.

[0038] The terms “optional” or “optionally” mean that the event or situation described below may or may not occur, and the description includes both cases in which the event or situation occurs and cases in which the event or situation does not occur. For example, “optionally substituted alkyl” means “alkyl” or “substituted alkyl” as defined above. Furthermore, an optionally substituted group may be unsubstituted (e.g., -CH2CH3), fully substituted (e.g., -CF2CF3), monosubstituted (e.g., -CH2CH2F), or substituted to any degree between full substitution and monosubstituted (e.g., -CH2CHF2, -CH2CF3, -CF2CH3, -CFHCHF2, etc.). Those skilled in the art will understand that for any group containing one or more substituents, such a group is not intended to introduce any substitution or substitution pattern that is spatially impractical and / or synthetically infeasible. Therefore, any substituent described should be generally understood to have a maximum molecular weight of about 1,000 Daltons and more typically up to about 500 Daltons.

[0039] "Effective dose" or "therapeutic effective dose" refers to the amount of a compound administered to a mammalian subject as a single dose or as part of a series of doses that effectively produces the desired therapeutic effect.

[0040] As used herein, the terms “synergistic effect” or “synergistic effect” when used in conjunction with a combination of agents mean any measured effect of that combination that is greater than the sum of the effects of the individual agents.

[0041] "Treatment" of an individual (e.g., a mammal, such as a human) or cell refers to any type of intervention intended to alter the natural course of disease in an individual or cell. In some embodiments, treatment includes administering a pharmaceutical composition after triggering a pathological event or exposure to a pathogen, and includes stabilizing the condition (e.g., preventing the condition from worsening) or alleviating the condition.

[0042] As used herein, the term “acceptable” in relation to formulations, compositions or ingredients means that it does not have a lasting harmful effect on the general health of the person being treated.

[0043] As used herein, the terms “administer,” “administering,” “administration,” and similar terms refer to methods that enable the delivery of a compound or composition to a desired biological site of action. These methods include, but are not limited to, oral, duodenal, parenteral (including intravenous, subcutaneous, intraperitoneal, intramuscular, intravascular, or infusion), local, and rectal administration. Those skilled in the art are familiar with administration techniques that can be used with the compounds and methods described herein. In some embodiments, the compounds and compositions described herein are administered orally.

[0044] As used herein, the terms “enhance” or “enhancing” mean to increase or prolong the potency or duration of a desired effect. Therefore, in relation to enhancing the effect of a therapeutic agent, the term “enhancement” refers to the ability to increase or prolong the potency or duration of the effect of other therapeutic agents on the system. As used herein, “enhancing effective amount” means an amount sufficient to enhance the effect of other therapeutic agents on the desired system.

[0045] The term "object" or "patient" encompasses mammals. Examples of mammals include, but are not limited to, any member of the mammal class: humans; non-human primates such as chimpanzees and other ape and monkey species; livestock such as cattle, horses, sheep, goats, and pigs; domestic animals such as rabbits, dogs, and cats; laboratory animals, including rodents such as rats, mice, and guinea pigs; and similar animals. In one respect, the mammal is human.

[0046] compound This document describes compounds of formula (I), (I'), (Ia), (II), (III), (IV), (V), or (VI), or pharmaceutically acceptable salts or solvates thereof, which are KAT6A inhibitors and are indicated for the treatment of diseases or conditions associated with KAT6A inhibition. In some embodiments, compounds of formula (I), (I'), (Ia), (II), (III), (IV), (V), or (VI), or pharmaceutically acceptable salts or solvates thereof, may be used to treat cancer.

[0047] In some embodiments, the compound of formula (I) disclosed herein, or a pharmaceutically acceptable salt or solvate thereof: ; in: Y 1 For CR 1a Or N; Y 2 For CR 2a Or N; Y3 For CR 3a Or N; Y 4 For CR 4a Or N; Y 5 For CR 5a Or N; Z 1 For CR 1b Or N; Z 2 For CR 2b Or N; Z 3 For CR 3b Or N; where Y 1 Y 2 Y 3 Y 4 Y 5 Z 1 Z 2 and Z 3 At least one of them is N; X is selected from -C(R) 6 (R) 6a -, -O- and -N(R) 7 )-; R 1 C 1-9 heteroaryl groups, which may optionally be selected from one, two or three R groups. 15a Substitution of groups; R 1a R 2a R 3a R 4a R 5a R 1b R 2b and R 3b Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -SF5, -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two or three of R... 15b Substitution of groups; R 6 and R 6a Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R)10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; R 7 Selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 10 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 11 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 12 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 13 Selected independently from C 1-6 Alkyl, C 2-6alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl; and Each R 15a and each R 15b Each is independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13-C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -CH2-C 3-10 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 heteroaryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13-OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ).

[0048] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 1 Let N be the number of elements in the array.

[0049] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 2 For CR 2a In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 2 Let N be the number of elements in the array.

[0050] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 3 For CR 3a In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 3 Let N be the number of elements in the array.

[0051] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 4 For CR 4a In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 4 Let N be the number of elements in the array.

[0052] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 5 For CR 5a In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 5 Let N be the number of elements in the array.

[0053] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a And Y 5 For CR 5a .

[0054] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a Y 5 For CR 5a And R 1a and R 5a Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a Y 5 For CR 5a And R 1a and R 5a Independently selected from hydrogen and -OR 10 In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a Y 5 For CR 5a And R 1a and R 5a For -OR 10 In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a Y 5 For CR 5a R 1a and R 5a For -OR 10 And R 10 C 1-6 Alkyl group. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, Y 1 For CR 1a Y 5 For CR5a R 1a and R 5a For -OR 10 And R 10 It is -CH3.

[0055] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvate, Z 1 For CR 1b In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Z 1 Let N be the number of elements in the array.

[0056] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvate, Z 2 For CR 2b In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Z 2 Let N be the number of elements in the array.

[0057] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvate, Z 3 For CR 3b In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Z 3 Let N be the number of elements in the array.

[0058] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a ;Y 2 For CR 2a ;Y 3 For CR 3a ;Y 4 For CR 4a ;Y 5 For CR 5a Z 1 For CR 1b Z 2 For CR 2b And Z 3 For CR 3b In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a ;Y 2 For N; Y 3 For CR 3a ;Y 4 For CR 4a ;Y 5 For CR 5a Z 1 For CR1b Z 2 For CR 2b And Z 3 For CR 3b In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, in Y 1 Y 2 Y 3 Y 4 Y 5 Z 1 Z 2 and Z 3 In the middle, only Y 2 For N. In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvate, Y 1 Y 2 Y 3 Y 4 Y 5 Z 1 Z 2 and Z 3 Only one of them is N. In some implementations, when Y 2 When it is N, then R 1a and R 5a For -OR 10 In some implementations, when Y 2 When it is N, then R 1a and R 5a Independently selected from -OC 1-6 Alkyl and -OC 1-6 Halogenated alkyl groups. In some embodiments, when Y... 2 When it is N, then R 1a and R 5a It is -OCH3.

[0059] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 2 For N; Y 3 For CR 3a And Y 4 For CR 4a In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 2 For CR 2a ;Y 3 Let N be the number of elements; and Y be the number of elements. 4 For CR 4a In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 2 For N; Y 3 For CR 3a And Y4 For N. In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvate, Y 2 For CR 2a ;Y 3 For CR 3a And Y 4 For CR 4a .

[0060] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a ;Y 5 For CR 5a ;Y 2 For N; Y 3 For CR 3a And Y 4 For CR 4a In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a ;Y 5 For CR 5a ;Y 2 For CR 2a ;Y 3 Let N be the number of elements; and Y be the number of elements. 4 For CR 4a In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a ;Y 5 For CR 5a ;Y 2 For N; Y 3 For CR 3a And Y 4 For N. In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvate, Y 1 For CR 1a ;Y 5 For CR 5a ;Y 2 For CR 2a ;Y 3 For CR 3a And Y 4 For CR 4a .

[0061] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvate, Z 1 For CR 1b Z 2 For CR 2b And Z3 For CR 3b In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Z 1 For N; Z 2 For CR 2b And Z 3 For CR 3b In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Z 1 For CR 1b Z 2 Let N be Z; and Z be Z. 3 For CR 3b In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Z 1 For CR 1b Z 2 For CR 2b And Z 3 Let N be the number of elements in the array.

[0062] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 2a R 3a R 4a R 1b R 2b and R 3b Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 2a R 3a R 4a R 1b R 2b and R 3b Independently selected from hydrogen, halogens and C 1-6 Alkyl group. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 2a R 3a R 4a R 1b R 2b and R 3b For hydrogen. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1b and R 2b For hydrogen, R 3b For -OR 10 And R 10 C 1-6Alkyl group. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1b and R 2b For hydrogen, R 3b For -OR 10 R 10 C is replaced by one, two or three halogens 1-6 alkyl.

[0063] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 1a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 1a For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 1a It is hydrogen. In some implementations, R 1a C 1-6 Alkyl group. In some embodiments, R 1a C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 1a C 1-6 Alkyl group. In some embodiments, R 1a It is -OCF3.

[0064] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 2a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 2a For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 2a It is hydrogen. In some implementations, R 2a C 1-6 Alkyl group. In some embodiments, R 2a C 1-6 Alkoxy group, wherein the alkoxy group is optionally substituted with one, two or three halogens.

[0065] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 3a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -OR 10 -SR 10 Or -SF5, where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl groups are optionally surrounded by one, two, or three groups selected from R 15b The group is substituted. In some embodiments, R 3a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl or C 3-6 cycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group and C 3-6 The cycloalkyl group is optionally substituted. In some embodiments, R 3a For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 Alkyne group. In some embodiments, R 3a It is hydrogen. In some implementations, R 3a C 1-6 Alkyl group. In some embodiments, R 3a C 1-6 Alkyl group. In some embodiments, R 3a C 1-6 Halogenated alkyl groups. In some embodiments, R 3a C 2-6 Alkenyl. In some embodiments, R 3a C 2-6 Alkyne group.

[0066] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 4a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 4aFor hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 4a It is hydrogen. In some implementations, R 4a C 1-6 Alkyl group. In some embodiments, R 4a C 1-6 Alkoxy group, wherein the alkoxy group is optionally substituted with one, two or three halogens.

[0067] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 5a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 5a For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 5a It is hydrogen. In some implementations, R 5a C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 5a C 1-6 Alkyl group. In some embodiments, R 5a C 1-3 Alkyl group. In some embodiments, R 5a It is -OCH3.

[0068] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 1b For hydrogen, halogen, C 1-6 Alkyl or C 1-6 Haloalkyl, wherein C 1-6 Alkyl groups are optionally composed of one, two, or three selected from R 15b The group is substituted. In some embodiments, R 1b It is hydrogen. In some implementations, R 1b It is a halogen. In some implementations, R 1b C 1-6 Alkyl group. In some embodiments, R 1b C 1-6 Halogenated alkyl groups.

[0069] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 2b For hydrogen, halogen, C 1-6 Alkyl or C 1-6 Haloalkyl, wherein C 1-6 Alkyl groups are optionally composed of one, two, or three selected from R 15b The group is substituted. In some embodiments, R 2b It is hydrogen. In some implementations, R 2b It is a halogen. In some implementations, R 1b C 1-6 Alkyl group. In some embodiments, R 1b C 1-6 Halogenated alkyl groups.

[0070] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 3b For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 3b For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 3b It is hydrogen. In some implementations, R 3b C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 3b C 1-6 Alkyl group. In some embodiments, R 3b C 1-3 Alkyl group. In some embodiments, R 3b C 1-3 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 3b For -OCH3. In some implementations, R 3b For -OCH2F. In some implementations, R 3b For -OCF3. In some implementations, R 3b For -OCHF2. In some implementations, R 3b It is -OCH2CF3.

[0071] In some embodiments of compounds of formula (I) or pharmaceutically acceptable salts or solvates thereof, X is -C(R 6 (R) 6aIn some embodiments of compounds of formula (I) or pharmaceutically acceptable salts or solvates thereof, X is -C(R) 6 (R) 6a )-and R 6 and R 6a Independently selected from hydrogen, halogen, C 1-6 Alkyl and -OH. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, X is -C(R 6 (R) 6a )-and R 6 and R 6a It is hydrogen.

[0072] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, X is -O-.

[0073] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, X is -N(R 7 In some embodiments of compounds of formula (I) or pharmaceutically acceptable salts or solvates thereof, X is -N(R) 7 )-and R 7 X is hydrogen. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, X is -N(R 7 )-and R 7 C 1-6 alkyl.

[0074] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 1 C is arbitrarily replaced 1-9 heteroaryl. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5- or 6-membered heteroaryl group. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5-membered heteroaryl group. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 6-membered heteroaryl group. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 It is a monocyclic heteroaryl group. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 It is a bicyclic heteroaryl group. In some embodiments, R 1 Optionally selected by one, two or three from R 15aThe group is substituted. In some embodiments, R 1 Optionally selected by one, two or three halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and C 1-6 Alkyl group substitution. In some embodiments, R 1 Optionally, it is selected from one, two, or three groups: oxo, -CN, amino, OH, halogen, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy and C 3-6 Cycloalkyl groups are substituted.

[0075] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are optionally selected by one, two, or three of R... 15a The group is substituted. In some embodiments of compounds of formula (I) or pharmaceutically acceptable salts or solvates thereof, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The group is substituted. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The groups are substituted and each R 15a Independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, are selected from R 15a The group is substituted and R15a Selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 .

[0076] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are optionally selected by one, two, or three of R... 15a The group is substituted. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are selected from R. 15a The group is substituted. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are selected from R. 15a The groups are substituted and each R 15a Independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl group is a derivative of R. 15a The group is substituted and R 15a Selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 .

[0077] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazoleyl, isoxazolyl, oxazolyl, and pyridyl, wherein the pyrazolyl, imidazoleyl, isoxazolyl, oxazolyl, and pyridyl groups are not substituted. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are not substituted. In some embodiments of compounds of formula (I) or pharmaceutically acceptable salts or solvates thereof, R 1 The pyrazol group is unsubstituted. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 The imidazole group is unsubstituted. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 R is an unsubstituted isoxazolyl group. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 The oxazolyl group is unsubstituted. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 R is an unsubstituted pyridinyl group. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 The thiazolyl group is unsubstituted. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 R is an unsubstituted pyrimidinyl group. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 1 It is an unsubstituted pyridazinyl group.

[0078] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 1 Selected from In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 1 Selected from Each of them is optionally controlled by 1, 2 or 3 R 15a Replacement. In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R1 for In some implementations, R 1 for .

[0079] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Selected from .

[0080] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 10 For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-6 Cycloalkyl. In some embodiments, R 10 For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-6 cycloalkyl, wherein C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one, two, or three groups selected from halogens and hydrogen. In some embodiments, R 10 For hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups. In some embodiments, R 10 C 1-6 Alkyl or C 1-6 Halogenated alkyl groups. In some embodiments, R 10 It is hydrogen. In some implementations, R 10 For -CH3. In some implementations, R 10 For -CH2F. In some implementations, R 10 For -CHF2. In some implementations, R 10 For -CH2CF3. In some implementations, R 10 It is -CF3.

[0081] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 11 For hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups. In some embodiments, R 11 For hydrogen. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 11 C 1-6 alkyl.

[0082] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 12 For hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups. In some embodiments, R 12 For hydrogen. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 12 C 1-6 alkyl.

[0083] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, R 13 C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-6 Cycloalkyl. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts or solvates, R 13 C 1-6 Alkyl or C 1-6 Halogenated alkyl groups.

[0084] In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvate, each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (I), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R)10 (R) 11 In some embodiments of the compounds of formula (I), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (I), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 .

[0085] In some embodiments of the compound of formula (I), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compounds of formula (I), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (I), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (I), each R 15a Each R 15b and each R 15c Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (I), each R 15a Each R 15b and each R 15c Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (I), each R 15a Each R 15b and each R15c Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (I), each R 15a Each R 15b and each R 15c Independently for -OR 10 .

[0086] In some embodiments, this document discloses a compound of formula (Ia) or a pharmaceutically acceptable salt or solvate thereof: ; in: Y 2 For CR 2a Or N; Y 3 For CR 3a Or N; Y 4 For CR 4a Or N; Z 1 For CR 1b Or N; Z 2 For CR 2b Or N; Z 3 For CR 3b Or N; where Y 2 Y 3 Y 4 Z 1 Z 2 and Z 3 At least one of them is N; X is selected from -C(R) 6 (R) 6a -, -O- and -N(R) 7 )-; R 1 C 1-9 heteroaryl groups, which may optionally be selected from one, two or three R groups. 15a Substitution of groups; R 1a R 2a R 3a R 4a R 5a R 1b R 2b and R 3b Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -SF5, -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two or three of R... 15b Substitution of groups; R 6 and R 6a Independently selected from hydrogen, halogen, C 1-6 Alkyl, C1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; R 7 Selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 10 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10Aryl and C 1-9 Mixed aromatics; Each R 11 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 12 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 13 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl; and Each R 15a and each R 15b Each is independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R)10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -CH2-C 3-10 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 heteroaryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ).

[0087] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 1a and R 5a Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1a and R 5a Independently selected from hydrogen and -OR 10 In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1a and R 5a For -OR 10 In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1a and R 5aFor -OR 10 And R 10 C 1-6 Alkyl group. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1a and R 5a For -OR 10 And R 10 It is -CH3.

[0088] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Y 2 For N; Y 3 For CR 3a And Y 4 For CR 4a In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Y 2 For CR 2a ;Y 3 Let N be the number of elements; and Y be the number of elements. 4 For CR 4a In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Y 2 For N; Y 3 For CR 3a And Y 4 For N. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, Y 2 For CR 2a ;Y 3 For CR 3a And Y 4 For CR 4a .

[0089] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Y 2 For CR 2a In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Y 2 Let N be the number of elements in the array.

[0090] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Y 3 For CR 3a In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Y 3 Let N be the number of elements in the array.

[0091] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Y 4 For CR4a In some embodiments of the compound of formula (I) or its pharmaceutically acceptable salt or solvation, Y 4 Let N be the number of elements in the array.

[0092] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Y 2 For N; Y 3 For CR 3a And Y 4 For CR 4a In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Y 2 For CR 2a ;Y 3 Let N be the number of elements; and Y be the number of elements. 4 For CR 4a In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Y 2 For N; Y 3 For CR 3a And Y 4 For N. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, Y 2 For CR 2a ;Y 3 For CR 3a And Y 4 For CR 4a .

[0093] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Z 1 For CR 1b Z 2 For CR 2b And Z 3 For CR 3b In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Z 1 For N; Z 2 For CR 2b And Z 3 For CR 3b In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Z 1 For CR 1b Z 2 Let N be Z; and Z be Z. 3 For CR 3b In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Z 1 For CR 1b Z2 For CR 2b And Z 3 Let N be the number of elements in the array.

[0094] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Z 1 For CR 1b In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Z 1 Let N be the number of elements in the array.

[0095] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Z 2 For CR 2b In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Z 2 Let N be the number of elements in the array.

[0096] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Z 3 For CR 3b In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Z 3 Let N be the number of elements in the array.

[0097] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a ;Y 2 For CR 2a ;Y 3 For CR 3a ;Y 4 For CR 4a ;Y 5 For CR 5a Z 1 For CR 1b Z 2 For CR 2b And Z 3 For CR 3b In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a ;Y 2 For N; Y 3 For CR 3a ;Y 4 For CR 4a ;Y 5 For CR 5a Z 1 For CR 1b Z 2For CR 2b And Z 3 For CR 3b In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, in Y 1 Y 2 Y 3 Y 4 Y 5 Z 1 Z 2 and Z 3 In the middle, only Y 2 For N. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, Y 1 Y 2 Y 3 Y 4 Y 5 Z 1 Z 2 and Z 3 Only one of them is N. In some implementations, when Y 2 When it is N, then R 1a and R 5a For -OR 10 In some implementations, when Y 2 When it is N, then R 1a and R 5a Independently selected from -OC 1-6 Alkyl and -OC 1-6 Halogenated alkyl groups. In some embodiments, when Y... 2 When it is N, then R 1a and R 5a It is -OCH3.

[0098] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 2a R 3a R 4a R 1b R 2b and R 3b Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 2a R 3a R 4a R 1b R 2b and R 3b Independently selected from hydrogen, halogens and C 1-6Alkyl group. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 2a R 3a R 4a R 1b R 2b and R 3b For hydrogen. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1b and R 2b For hydrogen, R 3b For -OR 10 And R 10 C 1-6 Alkyl group. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1b and R 2b For hydrogen, R 3b For -OR 10 R 10 C is replaced by one, two or three halogens 1-6 alkyl.

[0099] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 1a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 1a For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 1a It is hydrogen. In some implementations, R 1a C 1-6 Alkyl group. In some embodiments, R 1a C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 1a C 1-6 Alkyl groups. In some implementations, 1a It is -OCF3.

[0100] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 2a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 2a For hydrogen, C1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 2a It is hydrogen. In some implementations, R 2a C 1-6 Alkyl group. In some embodiments, R 2a C 1-6 Alkoxy group, wherein the alkoxy group is optionally substituted with one, two or three halogens.

[0101] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 3a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -OR 10 -SR 10 Or -SF5, where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl groups are optionally surrounded by one, two, or three groups selected from R 15b The group is substituted. In some embodiments, R 3a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl or C 3-6 cycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group and C 3-6 The cycloalkyl group is optionally substituted. In some embodiments, R 3a For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 Alkyne group. In some embodiments, R 3a It is hydrogen. In some implementations, R 3a C 1-6 Alkyl group. In some embodiments, R 3a C 1-6 Alkyl group. In some embodiments, R 3a C 1-6Halogenated alkyl groups. In some embodiments, R 3a C 2-6 Alkenyl. In some embodiments, R 3a C 2-6 Alkyne group.

[0102] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 4a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 4a For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 4a It is hydrogen. In some implementations, R 4a C 1-6 Alkyl group. In some embodiments, R 4a C 1-6 Alkoxy group, wherein the alkoxy group is optionally substituted with one, two or three halogens.

[0103] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 5a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 5a For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 5a It is hydrogen. In some implementations, R 5a C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 5a C 1-6 Alkyl group. In some embodiments, R 5a C 1-3 Alkyl group. In some embodiments, R 5a It is -OCH3.

[0104] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 1b For hydrogen, halogen, C 1-6 Alkyl or C 1-6Haloalkyl, wherein C 1-6 Alkyl groups are optionally composed of one, two, or three selected from R 15b The group is substituted. In some embodiments, R 1b It is hydrogen. In some implementations, R 1b It is a halogen. In some implementations, R 1b C 1-6 Alkyl group. In some embodiments, R 1b C 1-6 Halogenated alkyl groups.

[0105] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 2b For hydrogen, halogen, C 1-6 Alkyl or C 1-6 Haloalkyl, wherein C 1-6 Alkyl groups are optionally composed of one, two, or three selected from R 15b The group is substituted. In some embodiments, R 2b It is hydrogen. In some implementations, R 2b It is a halogen. In some implementations, R 1b C 1-6 Alkyl group. In some embodiments, R 1b C 1-6 Halogenated alkyl groups.

[0106] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 3b For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 3b For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 3b It is hydrogen. In some implementations, R 3b C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 3b C 1-6 Alkyl group. In some embodiments, R 3b C 1-3 Alkyl group. In some embodiments, R 3b C 1-3 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 3bFor -OCH3. In some implementations, R 3b For -OCH2F. In some implementations, R 3b For -OCF3. In some implementations, R 3b For -OCHF2. In some implementations, R 3b It is -OCH2CF3.

[0107] In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, X is -C(R 6 (R) 6a In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, X is -C(R) 6 (R) 6a )-and R 6 and R 6a Independently selected from hydrogen, halogen, C 1-6 Alkyl and -OH. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, X is -C(R 6 (R) 6a )-and R 6 and R 6a It is hydrogen.

[0108] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, X is -O-.

[0109] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, X is -N(R 7 In some embodiments of compounds of formula (Ia) or pharmaceutically acceptable salts or solvates thereof, X is -N(R) 7 )-and R 7 X is hydrogen. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, X is -N(R) 7 )-and R 7 C 1-6 alkyl.

[0110] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 1 C is arbitrarily replaced 1-9 Heteroaryl. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5- or 6-membered heteroaryl group. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1The substituted 5-membered heteroaryl group. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 6-membered heteroaryl group. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 It is a monocyclic heteroaryl group. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 It is a bicyclic heteroaryl group. In some embodiments, R 1 Optionally selected by one, two or three from R 15a The group is substituted. In some embodiments, R 1 Optionally selected by one, two or three halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and C 1-6 Alkyl group substitution. In some embodiments, R 1 Optionally, it is selected from one, two, or three groups: oxo, -CN, amino, OH, halogen, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy and C 3-6 Cycloalkyl groups are substituted.

[0111] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are optionally selected by one, two, or three of R... 15a The group is substituted. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The group is substituted. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15aThe groups are substituted and each R 15a Independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, are selected from R 15a The group is substituted and R 15a Selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 .

[0112] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are optionally selected by one, two, or three of R... 15a The group is substituted. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are selected from R. 15a The group is substituted. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are selected from R. 15a The groups are substituted and each R 15a Independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl group is a derivative of R. 15a The group is substituted and R 15aSelected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 .

[0113] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are not substituted. In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazoleyl, isoxazolyl, oxazolyl, and pyridyl, wherein the pyrazolyl, imidazoleyl, isoxazolyl, oxazolyl, and pyridyl groups are not substituted. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 The pyrazol group is unsubstituted. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 The imidazole group is unsubstituted. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 The isoxazolyl group is unsubstituted. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 The oxazolyl group is unsubstituted. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 R is an unsubstituted pyridinyl group. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 The thiazole group is unsubstituted. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 R is an unsubstituted pyrimidinyl group. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 It is an unsubstituted pyridazinyl group.

[0114] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 1 Selected from .

[0115] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 1 for .

[0116] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 1 for In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 1 Selected from Each of them is optionally controlled by 1, 2 or 3 R 15a Replacement. In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for .

[0117] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, Selected from .

[0118] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 10 For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-6 Cycloalkyl. In some embodiments, R 10 For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-6 cycloalkyl, wherein C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one, two, or three groups selected from halogens and hydrogen. In some embodiments, R 10 For hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups. In some embodiments, R 10 C 1-6 Alkyl or C 1-6Halogenated alkyl groups. In some embodiments, R 10 It is hydrogen. In some implementations, R 10 For -CH3. In some implementations, R 10 For -CH2F. In some implementations, R 10 For -CHF2. In some implementations, R 10 For -CH2CF3. In some implementations, R 10 It is -CF3.

[0119] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 11 For hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups. In some embodiments, R 11 For hydrogen. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 11 C 1-6 alkyl.

[0120] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 12 For hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups. In some embodiments, R 12 For hydrogen. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 12 C 1-6 alkyl.

[0121] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, R 13 C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-6 Cycloalkyl. In some embodiments of compounds of formula (Ia) or their pharmaceutically acceptable salts or solvates, R 13 C 1-6 Alkyl or C 1-6 Halogenated alkyl groups.

[0122] In some embodiments of the compound of formula (Ia) or its pharmaceutically acceptable salt or solvation, each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (Ia), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (Ia), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (Ia), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 .

[0123] In some embodiments of the compound of formula (Ia), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compounds of formula (Ia), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (Ia), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (Ia), each R 15a Each R 15b and each R 15c Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (Ia), each R 15a Each R 15b and each R 15c Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (Ia), each R 15a Each R 15b and each R 15c Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (Ia), each R 15a Each R 15b and each R 15c Independently for -OR 10 .

[0124] In some embodiments, the compound of formula (I') disclosed herein, or a pharmaceutically acceptable salt or solvate thereof: ; in: Y 1 For CR 1a Or N; Y 2 For CR 2a Or N; Y 3 For CR 3a Or N; Y 4 For CR 4a Or N; Y 5 For CR 5a Or N; Z 1 For CR 1b Or N; Z 2 For CR 2b Or N; Z3 For CR 3b Or N; X is -O- or -S-; or X is selected from -C(R) 6 (R) 6a - and -N(R) 7 )-, where Y 1 Y 2 Y 3 Y 4 Y 5 Z 1 Z 2 and Z 3 At least one of them is N; R 1 C 1-9 heteroaryl groups, which may optionally be selected from one, two or three R groups. 15a Substitution of groups; R 1a R 2a R 3a R 4a R 5a R 1b R 2b and R 3b Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -SF5, -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R)10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two or three of R... 15b Substitution of groups; R 6 and R 6a Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13-C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; R 7 Selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 10 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 11 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 12 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 13 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl; and Each R 15a and each R 15b Each is independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R)11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -CH2-C 3-10 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 heteroaryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11)-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ).

[0125] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, X is -O-. In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, X is -S-. In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, X is -O- or -S-. In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, X is -C(R) 6 (R) 6a )-, where Y 1 Y 2 Y 3 Y 4 Y 5 Z 1 Z 2 and Z 3 At least one of them is N. In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvate, X is -N(R 7 )-, where Y 1 Y 2 Y 3 Y 4 Y 5 Z 1 Z 2 and Z 3 At least one of them is N.

[0126] In some embodiments, the compound of formula (I') disclosed herein, or a pharmaceutically acceptable salt or solvate thereof: ; in: Y 1 For CR 1a Or N; Y 2 For CR 2a Or N; Y 3 For CR 3a Or N; Y4 For CR 4a Or N; Y 5 For CR 5a Or N; Z 1 For CR 1b Or N; Z 2 For CR 2b Or N; Z 3 For CR 3b Or N; X is -O-; R 1 C 1-9 heteroaryl groups, which may optionally be selected from one, two or three R groups. 15a Substitution of groups; R 1a R 2a R 3a R 4a R 5a R 1b R 2b and R 3b Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -SF5, -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R)11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two or three of R... 15b Substitution of groups; Each R 10 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 11 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 12 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 13 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl; and Each R 15a and each R 15b Each is independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -CH2-C 3-10 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 heteroaryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R)11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ).

[0127] In some embodiments, the compound of formula (I') has the structure of formula (Ia).

[0128] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, X is -O-. In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, X is -S-. In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, X is -C(R 6 (R) 6a In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, X is -N(R) 7 )-.

[0129] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 1 Let N be the number of elements in the array.

[0130] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Y 2 For CR 2a In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 2 Let N be the number of elements in the array.

[0131] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Y 3 For CR 3a In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 3 Let N be the number of elements in the array.

[0132] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Y 4 For CR 4a In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 4 Let N be the number of elements in the array.

[0133] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Y 5 For CR 5a In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 5 Let N be the number of elements in the array.

[0134] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a And Y 5 For CR 5a .

[0135] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a Y 5 For CR 5a And R 1a and R 5a Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 1 For CR 1a Y 5 For CR 5a And R 1a and R5a Independently selected from hydrogen and -OR 10 In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 1 For CR 1a Y 5 For CR 5a And R 1a and R 5a For -OR 10 In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 1 For CR 1a Y 5 For CR 5a R 1a and R 5a For -OR 10 And R 10 C 1-6 Alkyl group. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 1 For CR 1a Y 5 For CR 5a R 1a and R 5a For -OR 10 And R 10 It is -CH3.

[0136] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Y 2 For N; Y 3 For CR 3a And Y 4 For CR 4a In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 2 For CR 2a ;Y 3 Let N be the number of elements; and Y be the number of elements. 4 For CR 4a In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 2 For N; Y 3 For CR 3a And Y 4 For N. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 2 For CR 2a ;Y 3 For CR 3a And Y 4 For CR4a .

[0137] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a ;Y 5 For CR 5a ;Y 2 For N; Y 3 For CR 3a And Y 4 For CR 4a In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 1 For CR 1a ;Y 5 For CR 5a ;Y 2 For CR 2a ;Y 3 Let N be the number of elements; and Y be the number of elements. 4 For CR 4a In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 1 For CR 1a ;Y 5 For CR 5a ;Y 2 For N; Y 3 For CR 3a And Y 4 For N. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 1 For CR 1a ;Y 5 For CR 5a ;Y 2 For CR 2a ;Y 3 For CR 3a And Y 4 For CR 4a .

[0138] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Z 1 For CR 1b Z 2 For CR 2b And Z 3 For CR 3b In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Z 1 For N; Z 2 For CR 2b And Z 3For CR 3b In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Z 1 For CR 1b Z 2 Let N be Z; and Z be Z. 3 For CR 3b In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Z 1 For CR 1b Z 2 For CR 2b And Z 3 Let N be the number of elements in the array.

[0139] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Z 1 For CR 1b In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Z 1 Let N be the number of elements in the array.

[0140] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Z 2 For CR 2b In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Z 2 Let N be the number of elements in the array.

[0141] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Z 3 For CR 3b In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Z 3 Let N be the number of elements in the array.

[0142] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Y 1 For CR 1a ;Y 2 For CR 2a ;Y 3 For CR 3a ;Y 4 For CR 4a ;Y 5 For CR 5a Z 1 For CR 1b Z 2 For CR 2b And Z 3 For CR 3bIn some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 1 For CR 1a ;Y 2 For N; Y 3 For CR 3a ;Y 4 For CR 4a ;Y 5 For CR 5a Z 1 For CR 1b Z 2 For CR 2b And Z 3 For CR 3b In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, in Y 1 Y 2 Y 3 Y 4 Y 5 Z 1 Z 2 and Z 3 In the middle, only Y 2 For N. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, Y 1 Y 2 Y 3 Y 4 Y 5 Z 1 Z 2 and Z 3 Only one of them is N. In some implementations, when Y 2 When it is N, then R 1a and R 5a For -OR 10 In some implementations, when Y 2 When it is N, then R 1a and R 5a Independently selected from -OC 1-6 Alkyl and -OC 1-6 Halogenated alkyl groups. In some embodiments, when Y... 2 When it is N, then R 1a and R 5a It is -OCH3.

[0143] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 2a R 3a R 4a R 1b R 2b and R 3bIndependently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 2a R 3a R 4a R 1b R 2b and R 3b Independently selected from hydrogen, halogens and C 1-6 Alkyl group. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 2a R 3a R 4a R 1b R 2b and R 3b For hydrogen. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1b and R 2b For hydrogen, R 3b For -OR 10 And R 10 C 1-6 Alkyl group. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1b and R 2b For hydrogen, R 3b For -OR 10 R 10 C is replaced by one, two or three halogens 1-6 alkyl.

[0144] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 1a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 1a For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 1a It is hydrogen. In some implementations, R 1a C 1-6 Alkyl group. In some embodiments, R 1a C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 1aC 1-6 Alkyl groups. In some, 1a It is -OCF3.

[0145] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 2a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 2a For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 2a It is hydrogen. In some implementations, R 2a C 1-6 Alkyl group. In some embodiments, R 2a C 1-6 Alkoxy group, wherein the alkoxy group is optionally substituted with one, two or three halogens.

[0146] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 3a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -OR 10 -SR 10 Or -SF5, where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl groups are optionally surrounded by one, two, or three groups selected from R 15b The group is substituted. In some embodiments, R 3a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl or C 3-6 cycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group and C 3-6 The cycloalkyl group is optionally substituted. In some embodiments, R 3a For hydrogen, C 1-6 Alkyl, C1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 Alkyne group. In some embodiments, R 3a It is hydrogen. In some implementations, R 3a C 1-6 Alkyl group. In some embodiments, R 3a C 1-6 Alkyl group. In some embodiments, R 3a C 1-6 Halogenated alkyl groups. In some embodiments, R 3a C 2-6 Alkenyl. In some embodiments, R 3a C 2-6 Alkyne group.

[0147] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 4a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 4a For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 4a It is hydrogen. In some implementations, R 4a C 1-6 Alkyl group. In some embodiments, R 4a C 1-6 Alkoxy group, wherein the alkoxy group is optionally substituted with one, two or three halogens.

[0148] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 5a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 5a For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 5a It is hydrogen. In some implementations, R 5a C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 5a C1-6 Alkyl group. In some embodiments, R 5a C 1-3 Alkyl group. In some embodiments, R 5a It is -OCH3.

[0149] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 1b For hydrogen, halogen, C 1-6 Alkyl or C 1-6 Haloalkyl, wherein C 1-6 Alkyl groups are optionally composed of one, two, or three selected from R 15b The group is substituted. In some embodiments, R 1b It is hydrogen. In some implementations, R 1b It is a halogen. In some implementations, R 1b C 1-6 Alkyl group. In some embodiments, R 1b C 1-6 Halogenated alkyl groups.

[0150] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 2b For hydrogen, halogen, C 1-6 Alkyl or C 1-6 Haloalkyl, wherein C 1-6 Alkyl groups are optionally composed of one, two, or three selected from R 15b The group is substituted. In some embodiments, R 2b It is hydrogen. In some implementations, R 2b It is a halogen. In some implementations, R 1b C 1-6 Alkyl group. In some embodiments, R 1b C 1-6 Halogenated alkyl groups.

[0151] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 3b For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 3b For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 3b It is hydrogen. In some implementations, R 3b C 1-6An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 3b C 1-6 Alkyl group. In some embodiments, R 3b C 1-3 Alkyl group. In some embodiments, R 3b C 1-3 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 3b For -OCH3. In some implementations, R 3b For -OCH2F. In some implementations, R 3b For -OCF3. In some implementations, R 3b For -OCHF2. In some implementations, R 3b It is -OCH2CF3.

[0152] In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, X is -C(R 6 (R) 6a In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, X is -C(R) 6 (R) 6a )-and R 6 and R 6a Independently selected from hydrogen, halogen, C 1-6 Alkyl and -OH. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, X is -C(R 6 (R) 6a )-and R 6 and R 6a It is hydrogen.

[0153] In some embodiments of compounds of formula (I') or pharmaceutically acceptable salts or solvates thereof, X is -O-.

[0154] In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, X is -N(R 7 In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, X is -N(R) 7 )-and R 7 X is hydrogen. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, X is -N(R) 7 )-and R 7 C 1-6 alkyl.

[0155] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 1 C is arbitrarily replaced 1-9 heteroaryl. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5- or 6-membered heteroaryl group. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5-membered heteroaryl group. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 The substituted 6-membered heteroaryl group. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 It is a monocyclic heteroaryl group. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 It is a bicyclic heteroaryl group. In some embodiments, R 1 Optionally selected by one, two or three from R 15a The group is substituted. In some embodiments, R 1 Optionally selected by one, two or three halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and C 1-6 Alkyl group substitution. In some embodiments, R 1 Optionally, it is selected from one, two, or three groups: oxo, -CN, amino, OH, halogen, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy and C 3-6 Cycloalkyl groups are substituted.

[0156] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are optionally selected by one, two, or three of R... 15a The group substitution. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 C 1-9The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The group substitution. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The groups are substituted and each R 15a Independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, are selected from R 15a The group is substituted and R 15a Selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 .

[0157] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are optionally selected by one, two, or three of R... 15a The group substitution. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are selected from R. 15a The group substitution. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 C 1-9Heteroaryl groups, selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are selected from R. 15a The groups are substituted and each R 15a Independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl group is a derivative of R. 15a The group is substituted and R 15a Selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 .

[0158] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazoleyl, isoxazolyl, oxazolyl, and pyridyl, wherein the pyrazolyl, imidazoleyl, isoxazolyl, oxazolyl, and pyridyl groups are not substituted. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are not substituted. In some embodiments of compounds of formula (I') or pharmaceutically acceptable salts or solvates thereof, R 1 R is an unsubstituted pyrazolyl group. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 R is an unsubstituted imidazole group. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 R is an unsubstituted isoxazolyl group. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 The oxazolyl group is unsubstituted. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 R is an unsubstituted pyridinyl group. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1The thiazole group is unsubstituted. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 R is an unsubstituted pyrimidinyl group. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 It is an unsubstituted pyridazinyl group.

[0159] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 1 Selected from In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 1 Selected from Each of them is optionally controlled by 1, 2 or 3 R 15a Replacement. In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for .

[0160] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, Selected from .

[0161] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 10 For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-6 Cycloalkyl. In some embodiments, R 10 For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-6 cycloalkyl, wherein C 1-6 Alkyl and C 3-6The cycloalkyl group is optionally substituted with one, two, or three groups selected from halogens and hydrogen. In some embodiments, R 10 For hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups. In some embodiments, R 10 C 1-6 Alkyl or C 1-6 Halogenated alkyl groups. In some embodiments, R 10 It is hydrogen. In some implementations, R 10 For -CH3. In some implementations, R 10 For -CH2F. In some implementations, R 10 For -CHF2. In some implementations, R 10 For -CH2CF3. In some implementations, R 10 It is -CF3.

[0162] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 11 For hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups. In some embodiments, R 11 For hydrogen. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 11 C 1-6 alkyl.

[0163] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 12 For hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups. In some embodiments, R 12 For hydrogen. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 12 C 1-6 alkyl.

[0164] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, R 13 C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-6 Cycloalkyl. In some embodiments of compounds of formula (I') or their pharmaceutically acceptable salts or solvates, R 13 C 1-6 Alkyl or C 1-6 Halogenated alkyl groups.

[0165] In some embodiments of the compound of formula (I') or its pharmaceutically acceptable salt or solvation, each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (I'), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (I'), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (I'), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 .

[0166] In some embodiments of the compound of formula (I'), each R 15a Each R 15band each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compounds of formula (I'), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (I'), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (I'), each R 15a Each R 15b and each R 15c Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (I'), each R 15a Each R 15b and each R 15c Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (I'), each R 15a Each R 15b and each R 15c Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (I'), each R 15a Each R 15b and each R 15c Independently for -OR 10 .

[0167] In some embodiments of compounds of formula (I), (I'), or (Ia) or their pharmaceutically acceptable salts or solvates, Z 1 For CR 1b Z 2 For CR 2b Z 3 For CR 3b Each R 1a and each R 5a Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 And each R 2a Each R3a Each R 4a Each R 1b Each R 2b and each R 3b Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 , where R 10 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl or C 2-9 Heterocyclic alkyl. In some embodiments of compounds of formula (I), (I') or (Ia) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5- or 6-membered heteroaryl group. In some embodiments of compounds of formula (I), (I'), or (Ia) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5-membered heteroaryl group. In some embodiments of compounds of formula (I), (I'), or (Ia) or their pharmaceutically acceptable salts or solvates, R 1 The groups are pyrazolyl, imidazole, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazole, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The group substitution. In some embodiments of compounds of formula (I), (I') or (Ia) or their pharmaceutically acceptable salts or solvates, R 1 Selected from In some embodiments of compounds of formula (I), (I'), or (Ia) or their pharmaceutically acceptable salts or solvates, R 10 C 1-6 Alkyl or C 1-6 Halogenated alkyl groups.

[0168] In some embodiments, the compound of formula (II) disclosed herein, or a pharmaceutically acceptable salt or solvate thereof, is: ; in: X is selected from -C(R) 6 (R) 6a -, -O- and -N(R) 7 )-; R 1 C 1-9 heteroaryl groups, which may optionally be selected from one, two or three R groups. 15a Substitution of groups; R 6 and R 6aIndependently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; R 7 Selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; R 8a R 8b R 8c R 8d R 8e R 9b and R 9c Each is independently selected from hydrogen, halogen, and C. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -SF5, -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R)10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two or three of R... 15b Substitution of groups; R 9a Selected from C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 14 -SR 10 -SF5, -N(R) 10 (R) 11-C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl and C 3-6 The cycloalkyl group is selected from one, two or three R 15c The group is substituted, and C is in particular. 2-6 alkenyl, C 2-6 alkynyl group, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two or three of R... 15d Substitution of the group; or R 9a and R 9b Combine to form C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl or C 2-9 heteroaryl, of which C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl and C 2-9 The heteroaryl group is optionally selected by one, two or three of R... 15e Substitution of groups; Each R 10 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 11 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 12 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 13 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; R 14 Independently selected from hydrogen and C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 2-6 alkenyl, C 2-6 alkynyl group, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl; and Each R 15a Each R 15b Each R 15c Each R 15d and each R 15e Each is independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R)12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -CH2-C 3-10 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 heteroaryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12)C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ).

[0169] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 8a and R 8e Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 8a and R 8e Independently selected from hydrogen and -OR 10 In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 8a and R 8e For -OR 10 In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 8a and R 8e For -OR 10 And R 10 C 1-6 Alkyl. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 8a and R 8e For -OR10 And R 10 It is -CH3.

[0170] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 8a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 8a For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 8a It is hydrogen. In some implementations, R 8a C 1-6 Alkyl group. In some embodiments, R 8a C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 8a C 1-6 Alkyl group. In some embodiments, R 8a It is -OCF3.

[0171] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 8e For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 8e For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 8e It is hydrogen. In some implementations, R 8e C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 8e C 1-6 Alkyl group. In some embodiments, R 8e C 1-3 Alkyl group. In some embodiments, R 8e It is -OCH3.

[0172] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 8b R 8c R8d and R 9c Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 8b R 8c R 8d and R 9c Independently selected from hydrogen, halogens and C 1-6 Alkyl. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 8b R 8c R 8d and R 9c It is hydrogen.

[0173] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 8b For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 8b For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 8b It is hydrogen. In some implementations, R 8b C 1-6 Alkyl group. In some embodiments, R 8b C 1-6 Alkoxy group, wherein the alkoxy group is optionally substituted with one, two or three halogens.

[0174] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 8c For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -OR 10 -SR 10 Or -SF5, where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl groups are optionally surrounded by one, two, or three groups selected from R15b The group is substituted. In some embodiments, R 8c For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl or C 3-6 cycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group and C 3-6 The cycloalkyl group is optionally substituted. In some embodiments, R 8c For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 Alkyne group. In some embodiments, R 8c It is hydrogen. In some implementations, R 8c C 1-6 Alkyl group. In some embodiments, R 8c C 1-6 Alkyl group. In some embodiments, R 8c C 1-6 Halogenated alkyl groups. In some embodiments, R 8c C 2-6 Alkenyl. In some embodiments, R 8c C 2-6 Alkyne group.

[0175] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 8d For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 8d For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 8d It is hydrogen. In some implementations, R 8d C 1-6 Alkyl group. In some embodiments, R 8d C 1-6 Alkoxy group, wherein the alkoxy group is optionally substituted with one, two or three halogens.

[0176] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 9c For hydrogen, halogen, C 1-6Alkyl or C 1-6 Haloalkyl, wherein C 1-6 Alkyl groups are optionally composed of one, two, or three selected from R 15b The group is substituted. In some embodiments, R 9c It is hydrogen. In some implementations, R 9c It is a halogen. In some implementations, R 9c C 1-6 Alkyl group. In some embodiments, R 9c C 1-6 Halogenated alkyl groups.

[0177] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 9b Selected from hydrogen, halogens and C 1-6 Alkyl. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 9b For hydrogen. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 9b It is a halogen. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 9b C 1-6 Alkyl. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 9b It is -CH3.

[0178] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 9b For hydrogen, halogen, C 1-6 Alkyl or C 1-6 Haloalkyl, wherein C 1-6 Alkyl groups are optionally composed of one, two, or three selected from R 15b The group is substituted. In some embodiments, R 9b It is hydrogen. In some implementations, R 9b It is a halogen. In some implementations, R 9b C 1-6 Alkyl group. In some embodiments, R 9b C 1-6 Halogenated alkyl groups.

[0179] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 9a For -OR 14 In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 9a For -OR 14 And R14 C 1-6 Halogenated alkyl. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 9a For -OR 14 And R 14 For -CF3. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 9a For -OR 14 And R 14 It is -CHF2.

[0180] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 9a C 3-6 cycloalkyl groups, which are selected from one, two or three R groups 15c The group is substituted. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 9a C 3-6 cycloalkyl groups, which are selected from one, two or three R groups 15c The groups are substituted, and each R 15c Independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 9a C 3-6 cycloalkyl groups, which are selected from one, two or three R groups 15c The groups are substituted and each R 15c It is a halogen.

[0181] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 9a C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 14 In some implementations, R 9a C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OC 1-6 Halogenated alkyl groups. In some embodiments, R 9a -OC 1-6 Halogenated alkyl groups. In some embodiments, R 9a -OC 1-6 Halogenated alkyl groups. In some embodiments, R 9a It is -OCH2F.

[0182] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R9a With R 9b Combine to form C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl or C 2-9 heteroaryl, of which C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl and C 2-9 The heteroaryl group is optionally selected by one, two or three of R... 15e The group is substituted. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 9a With R 9b Combine to form C 2-9 Heterocyclic alkyl group, wherein the heterocyclic alkyl group is optionally composed of one, two, or three components selected from R 15e The group is substituted. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 9a With R 9b Combine to form C 2-9 Heterocyclic alkyl groups, optionally composed of one, two, or three elements selected from halogens, C 1-6 Alkyl and C 1-6 The alkyl group is substituted. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 10 For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-6 Cycloalkyl. In some embodiments, R 10 For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-6 cycloalkyl, wherein C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one, two, or three groups selected from halogens and hydrogen. In some embodiments, R 10 For hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups. In some embodiments, R 10 C 1-6 Alkyl or C 1-6 Halogenated alkyl groups. In some embodiments, R 10 It is hydrogen. In some implementations, R 10 For -CH3. In some implementations, R 10 For -CH2F. In some implementations, R 10 For -CHF2. In some implementations, R 10 For -CH2CF3. In some implementations, R 10 It is -CF3.

[0183] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 9a With R 9b Combinations are made to form 5- to 7-membered rings. In some implementations, R 9a With R 9b Combining them to form a 6-membered ring. In some implementations, R 9a With R 9b Combining to form cycloalkyl groups. In some embodiments, R 9a With R 9b Combining to form heterocyclic alkyl groups. In some embodiments, R 9a With R 9b Combining to form a ring containing one or two oxygen atoms and 0 to two nitrogen atoms. In some embodiments, R 9a With R 9b Combined to form a ring containing one oxygen atom.

[0184] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, for In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, for .

[0185] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 11 For hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups. In some embodiments, R 11 For hydrogen. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 11 C 1-6 alkyl.

[0186] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 12 For hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups. In some embodiments, R 12 For hydrogen. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 12 C 1-6 alkyl.

[0187] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 13 C 1-6Haloalkyl, C 1-6 Alkyl or C 3-6 Cycloalkyl. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 13 C 1-6 alkyl.

[0188] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 14 For hydrogen, C 1-6 Halogenated alkyl or C 3-6 Cycloalkyl. In some embodiments, R 14 It is hydrogen or C 1-6 Halogenated alkyl groups. In some embodiments, R 14 C 1-6 Halogenated alkyl groups. In some embodiments, R 14 It is hydrogen. In some implementations, R 14 For -CH2F. In some implementations, R 14 For -CH2CF3. In some implementations, R 14 It is -CF3.

[0189] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvate, each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (II), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (II), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (II), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 .

[0190] In some embodiments of the compound of formula (II), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compounds of formula (II), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (II), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (II), each R 15a Each R 15b and each R 15c Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (II), each R 15a Each R 15b and each R 15c Independently for C 1-6 Alkyl or -OR 10In some embodiments of the compounds of formula (II), each R 15a Each R 15b and each R 15c Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (II), each R 15a Each R 15b and each R 15c Independently for -OR 10 .

[0191] In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, X is -C(R 6 (R) 6a In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, X is -C(R) 6 (R) 6a )-and R 6 and R 6a Independently selected from hydrogen, halogen, C 1-6 Alkyl and -OH. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, X is -C(R 6 (R) 6a )-and R 6 and R 6a It is hydrogen.

[0192] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, X is -O-.

[0193] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, X is -N(R 7 In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, X is -N(R) 7 )-and R 7 X is hydrogen. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, X is -N(R) 7 )-and R 7 C 1-6 alkyl.

[0194] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 1 C is arbitrarily replaced 1-9 heteroaryl. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1The substituted 5- or 6-membered heteroaryl group. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5-membered heteroaryl group. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 6-membered heteroaryl group. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 It is a monocyclic heteroaryl group. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 It is a bicyclic heteroaryl group. In some embodiments, R 1 Optionally selected by one, two or three from R 15a The group is substituted. In some embodiments, R 1 Optionally selected by one, two or three halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and C 1-6 Alkyl group substitution. In some embodiments, R 1 Optionally, it is selected from one, two, or three groups: oxo, -CN, amino, OH, halogen, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy and C 3-6 Cycloalkyl groups are substituted.

[0195] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are optionally selected by one, two, or three of R... 15a The group is substituted. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The group is substituted. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The groups are substituted and each R 15a Independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, are selected from R 15a The group is substituted and R 15a Selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 .

[0196] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are optionally selected by one, two, or three of R... 15a The group is substituted. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are selected from R. 15a The group is substituted. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are selected from R. 15a The groups are substituted and each R 15a Independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 C1-9 The heteroaryl group is selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl group is a derivative of R. 15a The group is substituted and R 15a Selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 .

[0197] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazoleyl, isoxazolyl, oxazolyl, and pyridyl, wherein the pyrazolyl, imidazoleyl, isoxazolyl, oxazolyl, and pyridyl groups are not substituted. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are not substituted. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 The pyrazol group is unsubstituted. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 The imidazole group is unsubstituted. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 R is an unsubstituted isoxazolyl group. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 The oxazolyl group is unsubstituted. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 R is an unsubstituted pyridinyl group. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 The thiazole group is unsubstituted. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 It is an unsubstituted pyrimidinyl group. In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 It is an unsubstituted pyridazinyl group.

[0198] In some embodiments of the compound of formula (II) or its pharmaceutically acceptable salt or solvation, R 1 Selected from In some embodiments of compounds of formula (II) or their pharmaceutically acceptable salts or solvates, R 1 Selected from Each of them is optionally controlled by 1, 2 or 3 R 15a Replacement. In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for .

[0199] In some embodiments, the compound of formula (III) disclosed herein, or a pharmaceutically acceptable salt or solvate thereof: ; in: X is selected from -O- and -N(R) 7 )-; R 1 C 1-9 heteroaryl groups, which may optionally be selected from one, two or three R groups. 15a Substitution of groups; R 7 Selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; R 8a R 8b R 8c R 8d R 8e R 9b and R 9c Each is independently selected from hydrogen, halogen, and C. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -SF5, -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two or three of R... 15b Substitution of groups; R 9a Selected from hydrogen, C 1-6 Alkyl, C 3-6 cycloalkyl and -OR 14 ; Each R 10 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 11 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 12 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 13 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; R 14 Selected from C 1-6 Alkyl and C 3-6 cycloalkyl; and Each R 15a and each R 15b Each is independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -CH2-C 3-10 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 heteroaryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ).

[0200] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 8a and R 8e Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 8a and R 8e Independently selected from hydrogen and -OR 10 In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 8a and R 8e For -OR 10 In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 8a and R 8e For -OR 10 And R 10 C 1-6 Alkyl group. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 8a and R 8e For -OR 10 And R 10 It is -CH3.

[0201] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 8a For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 8a For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 8a It is hydrogen. In some implementations, R 8a C 1-6 Alkyl group. In some embodiments, R 8a C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 8a C 1-6 Alkyl group. In some embodiments, R 8a It is -OCF3.

[0202] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 8e For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 8e For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 8e It is hydrogen. In some implementations, R 8e C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 8e C 1-6 Alkyl group. In some embodiments, R 8e C 1-3 Alkyl group. In some embodiments, R 8e It is -OCH3.

[0203] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 8b R 8c R 8d and R 9c Independently selected from hydrogen, halogen, C 1-6 Alkyl, C1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 8b R 8c R 8d and R 9c Independently selected from hydrogen, halogens and C 1-6 Alkyl group. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 8b R 8c R 8d and R 9c It is hydrogen.

[0204] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 8b For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 8b For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 8b It is hydrogen. In some implementations, R 8b C 1-6 Alkyl group. In some embodiments, R 8b C 1-6 Alkoxy group, wherein the alkoxy group is optionally substituted with one, two or three halogens.

[0205] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 8c For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -OR 10 -SR 10 Or -SF5, where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl groups are optionally surrounded by one, two, or three groups selected from R 15b The group is substituted. In some embodiments, R 8c For hydrogen, halogen, C1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl or C 3-6 cycloalkyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group and C 3-6 The cycloalkyl group is optionally substituted. In some embodiments, R 8c For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 Alkyne group. In some embodiments, R 8c It is hydrogen. In some implementations, R 8c C 1-6 Alkyl group. In some embodiments, R 8c C 1-6 Alkyl group. In some embodiments, R 8c C 1-6 Halogenated alkyl groups. In some embodiments, R 8c C 2-6 Alkenyl. In some embodiments, R 8c C 2-6 Alkyne group.

[0206] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 8d For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some implementations, R 8d For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 1-6 An alkoxy group, wherein the alkoxy group is optionally substituted with one, two, or three halogens. In some embodiments, R 8d It is hydrogen. In some implementations, R 8d C 1-6 Alkyl group. In some embodiments, R 8d C 1-6 Alkoxy group, wherein the alkoxy group is optionally substituted with one, two or three halogens.

[0207] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9c For hydrogen, halogen, C 1-6 Alkyl or C 1-6 Haloalkyl, wherein C 1-6Alkyl groups are optionally composed of one, two, or three selected from R 15b The group is substituted. In some embodiments, R 9c It is hydrogen. In some implementations, R 9c It is a halogen. In some implementations, R 9c C 1-6 Alkyl group. In some embodiments, R 9c C 1-6 Halogenated alkyl groups.

[0208] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9b Selected from hydrogen, halogens and C 1-6 Alkyl group. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9b For hydrogen. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9b It is a halogen. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9b C 1-6 Alkyl group. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9b It is -CH3.

[0209] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9b For hydrogen, halogen, C 1-6 Alkyl or C 1-6 Haloalkyl, wherein C 1-6 Alkyl groups are optionally composed of one, two, or three selected from R 15b The group is substituted. In some embodiments, R 9b It is hydrogen. In some implementations, R 9b It is a halogen. In some implementations, R 9b C 1-6 Alkyl group. In some embodiments, R 9b C 1-6 Halogenated alkyl groups.

[0210] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9a For -OR 14 In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9a For -OR 14 And R 14 C 1-6Alkyl group. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9a For -OR 14 And R 14 For -CH3. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9a For -OR 14 And R 14 C 3-6 Cycloalkyl. In some embodiments, R 9a It is -OCH2F.

[0211] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9a C 1-6 Alkyl, C 3-6 cycloalkyl or -OR 14 In some implementations, R 9a C 1-6 Alkyl, C 1-6 cycloalkyl or C 1-6 Alkyl group. In some embodiments, R 9a C 1-6 Alkyl group. In some embodiments, R 9a C 1-3 Alkyl group.

[0212] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9a For hydrogen. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9a C 1-6 Alkyl group. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 9a C 3-6 Cycloalkyl. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, X is -O-.

[0213] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, X is -N(R 7 In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, X is -N(R) 7 )-and R 7 X is hydrogen. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, X is -N(R) 7 )-and R 7 C1-6 alkyl.

[0214] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 10 For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-6 Cycloalkyl. In some embodiments, R 10 For hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-6 cycloalkyl, wherein C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one, two, or three groups selected from halogens and hydrogen. In some embodiments, R 10 For hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups. In some embodiments, R 10 C 1-6 Alkyl or C 1-6 Halogenated alkyl groups. In some embodiments, R 10 It is hydrogen. In some implementations, R 10 For -CH3. In some implementations, R 10 For -CH2F. In some implementations, R 10 For -CHF2. In some implementations, R 10 For -CH2CF3. In some implementations, R 10 It is -CF3.

[0215] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 11 For hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups. In some embodiments, R 11 For hydrogen. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 11 C 1-6 alkyl.

[0216] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 12 For hydrogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups. In some embodiments, R 12 For hydrogen. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 12 C 1-6 alkyl.

[0217] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 13 C 1-6 Haloalkyl, C 1-6 Alkyl or C 3-6 Cycloalkyl. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 13 C 1-6 Alkyl group. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 13 C 1-6 Halogenated alkyl groups.

[0218] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 14 C 1-6 Alkyl or C 3-6 Cycloalkyl. In some embodiments, R 14 C 1-6 Alkyl group. In some embodiments, R 14 C 3-6 Cycloalkyl. In some embodiments, R 14 It is -CH3.

[0219] In some embodiments of the compound of formula (III) or its pharmaceutically acceptable salt or solvate, each R 15a and each R 15b Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (III), each R 15a and each R 15b Independently halogenated, oxo-, -CN, C1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (III), each R 15a and each R 15b Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (III), each R 15a and each R 15b Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 .

[0220] In some embodiments of the compounds of formula (III), each R 15a and each R 15b Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compounds of formula (III), each R 15a and each R 15b Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (III), each R 15a and each R 15b Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (III), each R 15a and each R 15b Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (III), each R 15a and each R 15b Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (III), each R 15a and each R 15b Independently for C 3-10 cycloalkyl or -OR10 In some embodiments of the compounds of formula (III), each R 15a and each R 15b Independently for -OR 10 .

[0221] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 C is arbitrarily replaced 1-9 heteroaryl. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5- or 6-membered heteroaryl group. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5-membered heteroaryl group. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 6-membered heteroaryl group. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 It is a monocyclic heteroaryl group. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 It is a bicyclic heteroaryl group. In some embodiments, R 1 Optionally selected by one, two or three from R 15a The group is substituted. In some embodiments, R 1 Optionally selected by one, two or three halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and C 1-6 Alkyl group substitution. In some embodiments, R 1 Optionally, it is selected from one, two, or three groups: oxo, -CN, amino, OH, halogen, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy and C 3-6 Cycloalkyl groups are substituted.

[0222] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are optionally selected by one, two, or three of R... 15aThe group is substituted. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The group is substituted. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The groups are substituted and each R 15a Independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, are selected from R 15a The group is substituted and R 15a Selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 .

[0223] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are optionally selected by one, two, or three of R... 15a The group is substituted. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are selected from R. 15aThe group is substituted. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl groups are selected from R. 15a The groups are substituted and each R 15a Independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl, wherein the pyrazolyl, imidazole, isoxazolyl, oxazolyl, and pyridinyl group is a derivative of R. 15a The group is substituted and R 15a Selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 .

[0224] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are not substituted. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazoleyl, isoxazolyl, oxazolyl, and pyridyl, wherein the pyrazolyl, imidazoleyl, isoxazolyl, oxazolyl, and pyridyl groups are not substituted. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 The pyrazol group is unsubstituted. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 The imidazole group is unsubstituted. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 The unsubstituted isoxazolyl group. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 The oxazolyl group is unsubstituted. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R1 It is an unsubstituted pyridinyl group. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 The thiazolyl group is unsubstituted. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 It is an unsubstituted pyrimidinyl group. In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 It is an unsubstituted pyridazinyl group.

[0225] In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 Selected from In some embodiments of compounds of formula (III) or their pharmaceutically acceptable salts or solvates, R 1 Selected from Each of them is optionally controlled by 1, 2 or 3 R 15a Replacement. In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for In some implementations, R 1 for .

[0226] This document covers any combination of groups described above with respect to various variables. Throughout the specification, those skilled in the art select groups and their substituents to provide stable moieties and compounds.

[0227] In some embodiments, this document provides a compound or a pharmaceutically acceptable salt or solvate thereof selected from:

[0228]

[0229] .

[0230] In some embodiments, a compound or a pharmaceutically acceptable salt or solvate thereof is described herein, wherein the compound is selected from the compounds in Table 1A: Table 1A. Exemplary Compounds

[0231]

[0232]

[0233]

[0234]

[0235]

[0236] In some embodiments, this document discloses a compound of formula (IV) or a pharmaceutically acceptable salt or solvate thereof: , in: R 2 C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 heteroaryl; each optionally selected from one, two, three or four R 15c Substitution of groups; Z 1 For CR 1b Or N; Z 2 For CR 2b Or N; Z 3 For CR 3b Or N; R 1 C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 heteroaryl; each optionally selected from one, two or three of R 15a Substitution of groups; R 1b R 2b and R 3b Independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -SF5, -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two or three of R... 15b Substitution of groups; or R 2b With R 3b Connected together to form C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C1-9 heteroaryl; of which C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two, three or four from R 15e Substitution of groups; Each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10(R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 or -CH2S(O)2N(R) 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -CH2-C 3-10 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 heteroaryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11-CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ); Each R 15e Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R)11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 or -CH2S(O)2N(R) 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -CH2-C 3-10 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 heteroaryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11-CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ); Or two R on adjacent carbons 15e They link together to form C2 subene groups; Or two R atoms on the same atom 15e Connected together to form C 3-6 cycloalkyl or C 2-9 Heterocyclic alkyl groups; each optionally substituted by one, two, or three independently selected from the following groups: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12)C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ); Or two R on different atoms 15e Connected together to form C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 Heteroaryl groups; each optionally substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R)11 ); Each R 10 Independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 11 Independently hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups; Each R 12 Independently hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups; and Each R 13 Independently hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatic compounds.

[0237] In some embodiments of the compound of formula (IV), R 2 C 6-10 Aryl or C 1-9 heteroaryl; each optionally selected from one, two, three or four R 15c Substitution of groups.

[0238] In some embodiments of the compound of formula (IV), R 2 C 1-9 heteroaryl groups, which may optionally be selected from one, two, three or four R groups. 15c Substitution of groups.

[0239] In some embodiments of the compound of formula (IV), R 2 It is a 5- or 6-membered heteroaryl group, which is optionally composed of one, two, three, or four groups selected from R. 15c Substitution of groups.

[0240] In some embodiments of the compound of formula (IV), R 2 It is a 6-membered heteroaryl group, which is optionally composed of one, two, three or four components selected from R. 15c Substitution of groups.

[0241] In some embodiments of the compound of formula (IV), R 2 It is a pyridinyl group, which is optionally surrounded by one, two, three or four groups selected from R. 15c Substitution of groups.

[0242] In some embodiments of the compound of formula (IV), R 2 It is a phenyl group, which is optionally composed of one, two, three or four radicals selected from R. 15c Substitution of groups.

[0243] In some embodiments of the compound of formula (IV), R 2 for .

[0244] In some embodiments of the compound of formula (IV), Z 1 For CR 1b Z 2 For CR 2b And Z 3 For CR 3b In some embodiments of the compound of formula (IV), Z 1 For N; Z 2 For CR2b And Z 3 For CR 3b In some embodiments of the compound of formula (IV), Z 1 For CR 1b Z 2 Let N be Z; and Z be Z. 3 For CR 3b In some embodiments of the compound of formula (IV), Z 1 For CR 1b Z 2 For CR 2b And Z 3 Let N be the number of elements in the array.

[0245] In some embodiments of the compound of formula (IV), R 1b R 2b and R 3b Independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -SF5, -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 ), where C 1-6 Alkyl, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two or three of R... 15b Substitution of groups.

[0246] In some embodiments of the compound of formula (IV), R 1b R 2b and R 3b Independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -OR 10 -SR 10 Or -SF5, where C 1-6 Alkyl, C 3-6 cycloalkyl and C 2-9Heterocyclic alkyl groups are optionally surrounded by one, two, or three groups selected from R 15b Substitution of groups.

[0247] In some embodiments of the compound of formula (IV), R 1b R 2b and R 3b Independently hydrogen, halogen, C 3-6 cycloalkyl, -OR 10 -SR 10 Or -SF5, where C 3-6 The cycloalkyl group is optionally surrounded by one, two, or three groups selected from R 15b Substitution of groups.

[0248] In some embodiments of the compound of formula (IV), R 1b R 2b and R 3b Independent of hydrogen, halogen, -OR 10 -SR 10 Or -SF5.

[0249] In some embodiments of the compound of formula (IV), R 1b R 2b and R 3b Independently hydrogen or -OR 10 .

[0250] In some embodiments of the compound of formula (IV), R 1b R 2b and R 3b It is hydrogen.

[0251] In some embodiments of the compound of formula (IV), R 1b It is hydrogen.

[0252] In some embodiments of the compound of formula (IV), R 2b With R 3b Connected together to form C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 heteroaryl; of which C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two, three or four from R 15e Substitution of groups.

[0253] In some embodiments of the compound of formula (IV), R 2b With R 3b Connected together to form C3-6 cycloalkyl or C 2-9 Heterocyclic alkyl; wherein C 3-6 cycloalkyl and C 2-9 Heterocyclic alkyl groups are optionally surrounded by one, two, three, or four selected from R 15e Substitution of groups.

[0254] In some embodiments of the compound of formula (IV), R 2b With R 3b Connected together to form C 2-9 Heterocyclic alkyl groups, optionally composed of one, two, three, or four selected from R 15e Substitution of groups.

[0255] In some embodiments of the compound of formula (IV), R 2b With R 3b Connected together to form C 2-6 Heterocyclic alkyl groups, optionally composed of one, two, three, or four selected from R 15e Substitution of groups.

[0256] In some embodiments of the compound of formula (IV), R 2b With R 3b Connected together to form C 6-9 Heterocyclic alkyl groups, optionally composed of one, two, three, or four selected from R 15e Substitution of groups.

[0257] In some embodiments of the compound of formula (IV), R 2b With R 3b They are linked together to form a 5- to 7-membered heterocyclic alkyl group containing one or two heteroatoms selected from O and N. In some embodiments of the compounds of formula (IV), R 2b With R 3b They are linked together to form a 6-membered heterocyclic alkyl group containing one of the heteroatoms that is O.

[0258] In some embodiments of the compounds of formula (IV), each R 15e Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R)10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 ).

[0259] In some embodiments of the compounds of formula (IV), each R 15e Independently halogenated, oxo-, -CN, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups.

[0260] In some embodiments of the compounds of formula (IV), each R 15e Independently halogen, oxo, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups.

[0261] In some embodiments of the compound of formula (IV), the two R on adjacent carbons 15e They link together to form C2 subene groups.

[0262] In some embodiments of the compound of formula (IV), the two R atoms on the same atom 15e Connected together to form C 3-6 cycloalkyl or C 2-9 Heterocyclic alkyl groups; each optionally substituted by one, two, or three independently selected from the following groups: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 and -N(R) 10 (R) 11 ).

[0263] In some embodiments of the compound of formula (IV), the two R atoms on the same atom 15e Connected together to form C 3-6 Cycloalkyl groups, optionally substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 and -N(R) 10 (R) 11 ).

[0264] In some embodiments of the compound of formula (IV), the two R atoms on the same atom 15eConnected together to form C 3-6 Cycloalkyl.

[0265] In some embodiments of the compound of formula (IV), the two R atoms on different atoms 15e Connected together to form C 3-6 cycloalkyl or C 2-9 Heterocyclic alkyl groups; each optionally substituted by one, two, or three independently selected from the following groups: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 and -N(R) 10 (R) 11 ).

[0266] In some embodiments of the compound of formula (IV), the two R atoms on different atoms 15e Connected together to form C 3-6 Cycloalkyl groups, optionally substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 and -N(R) 10 (R) 11 ).

[0267] In some embodiments of the compound of formula (IV), the two R atoms on different atoms 15e Connected together to form C 3-6 Cycloalkyl.

[0268] In some embodiments of the compound of formula (IV), R 2b and R 3b Connected together to form .

[0269] In some embodiments of the compound of formula (IV), R 1 C 6-10 Aryl or C 1-9 heteroaryl; each optionally selected from one, two or three of R 15a Substitution of groups.

[0270] In some embodiments of the compound of formula (IV), R 1 C 1-9 heteroaryl groups, which may optionally be selected from one, two or three R groups. 15a Substitution of groups.

[0271] In some embodiments of the compound of formula (IV), R 1 It is a 5- or 6-membered heteroaryl group, which is optionally composed of one, two, or three groups selected from R. 15a Substitution of groups.

[0272] In some embodiments of the compound of formula (IV), R 1 It is a 5-membered heteroaryl group, which is optionally composed of one, two, or three components selected from R. 15a Substitution of groups.

[0273] In some embodiments of compounds of formula (IV) or their pharmaceutically acceptable salts or solvates, R 1 C is arbitrarily replaced 1-9 heteroaryl. In some embodiments of compounds of formula (IV) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5- or 6-membered heteroaryl group. In some embodiments of compounds of formula (IV) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5-membered heteroaryl group. In some embodiments of compounds of formula (IV) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 6-membered heteroaryl group. In some embodiments of compounds of formula (IV) or their pharmaceutically acceptable salts or solvates, R 1 It is a monocyclic heteroaryl group. In some embodiments of compounds of formula (IV) or their pharmaceutically acceptable salts or solvates, R 1 It is a bicyclic heteroaryl group. In some embodiments, R 1 Optionally selected by one, two or three from R 15a The group is substituted. In some embodiments, R 1 Optionally selected by one, two or three halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and C 1-6 Alkyl group substitution. In some embodiments, R 1 Optionally, it is selected from one, two, or three groups: oxo, -CN, amino, OH, halogen, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy and C 3-6 Cycloalkyl groups are substituted.

[0274] In some embodiments of compounds of formula (IV) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are optionally selected by one, two, or three of R... 15a The group is substituted. In some embodiments of compounds of formula (IV) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The group is substituted. In some embodiments of compounds of formula (IV) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The groups are substituted and each R 15a Independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (IV) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, are selected from R 15a The group is substituted and R 15a Selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 .

[0275] In some embodiments of the compound of formula (IV), R 1 C is selected from pyrazolyl and thiazolyl groups. 1-9 Heteroaryl groups, wherein the pyrazolyl and thiazolyl groups are optionally selected from R by one, two, or three of them. 15a Substitution of groups.

[0276] In some embodiments of the compound of formula (IV), R 1 It is a thiazolyl group, which is optionally surrounded by one, two, or three groups selected from R. 15a Substitution of groups.

[0277] In some embodiments of the compound of formula (IV), R 1 It is a pyrazolyl group, which is optionally surrounded by one, two or three groups selected from R. 15a Substitution of groups.

[0278] In some embodiments of the compound of formula (IV), R 1 for .

[0279] In some embodiments of the compounds of formula (IV), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (IV), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (IV), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (IV), each R 15a Each R 15band each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 .

[0280] In some embodiments of the compounds of formula (IV), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15a Each R 15b and each R 15c Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15a Each R 15b and each R 15c Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15a Each R 15b and each R 15c Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15a Each R 15b and each R 15c Independently for -OR 10 .

[0281] In some embodiments of the compounds of formula (IV), each R 15a Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (IV), each R 15a Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (IV), each R 15a Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (IV), each R 15a Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15a Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15a Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15a Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15aIndependently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15a Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15a Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15a Independently for -OR 10 .

[0282] In some embodiments of the compounds of formula (IV), each R 15b Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (IV), each R 15b Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (IV), each R 15b Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (IV), each R 15b Independent of halogen, C1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 .

[0283] In some embodiments of the compounds of formula (IV), each R 15b Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15b Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15b Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15b Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15b Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15b Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15b Independently for -OR 10 .

[0284] In some embodiments of the compounds of formula (IV), each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (IV), each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (IV), each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (IV), each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 .

[0285] In some embodiments of the compounds of formula (IV), each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15c Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15c Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15c Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15c Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R 15c Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (IV), each R15c Independently for -OR 10 .

[0286] This document also discloses a compound of formula (V) or a pharmaceutically acceptable salt or solvate thereof: , in: R 2 C 1-9 heteroaryl groups, which may optionally be selected from one, two, three or four R groups. 15c Substitution of groups; Z 1 For CR 1b Or N; R 1 C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 heteroaryl; each optionally selected from one, two or three of R 15a Substitution of groups; R 1b For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -SF5, -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12)C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 or -CH2S(O)2N(R) 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two or three of R... 15b Substitution of groups; X is -C(R) 6 (R) 6a -, -S-, -O-, or -N(R) 7 )-; R 6 and R 6a Independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 or -CH2S(O)2N(R) 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; or R 6 With R 6a They link together to form oxygen; R 7 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Ring A is C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 Mixed aromatics; Each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 or -CH2S(O)2N(R) 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -CH2-C 3-10 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 heteroaryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R)10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ); Each R 15e Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 or -CH2S(O)2N(R) 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -CH2-C 3-10 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 heteroaryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R)10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ); Or two R on adjacent carbons 15e They link together to form C2 subene groups; Or two R atoms on the same atom 15e Connected together to form C 3-6 cycloalkyl or C 2-9 Heterocyclic alkyl groups; each optionally substituted by one, two, or three independently selected from the following groups: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13-S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ); Or two R on different atoms 15e Connected together to form C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 Heteroaryl groups; each optionally substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ); n is between 0 and 6; Each R 10 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 11 For hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups; Each R 12 For hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups; and Each R 13 For hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatic compounds.

[0287] In some embodiments of the compound of formula (V), R 2 It is a 5- or 6-membered heteroaryl group, which is optionally composed of one, two, three, or four groups selected from R. 15c Substitution of groups.

[0288] In some embodiments of the compound of formula (V), R 2 It is a 6-membered heteroaryl group, which is optionally composed of one, two, three or four components selected from R. 15c Substitution of groups.

[0289] In some embodiments of the compound of formula (V), R 2 It is a pyridinyl group, which is optionally surrounded by one, two, three or four groups selected from R. 15c Substitution of groups.

[0290] In some embodiments of the compound of formula (V), R 2 for .

[0291] In some embodiments of the compound of formula (V), ring A is C. 3-6 cycloalkyl or C 2-9 Heterocyclic alkyl groups.

[0292] In some embodiments of the compound of formula (V), ring A is C. 2-9 Heterocyclic alkyl groups.

[0293] In some embodiments of the compound of formula (V), ring A is C. 2-6 Heterocyclic alkyl groups.

[0294] In some embodiments of the compound of formula (V), ring A is C. 6-9Heterocyclic alkyl. In some embodiments of the compounds of formula (V), ring A is a 6-membered heterocyclic alkyl. In some embodiments of the compounds of formula (V), ring A is a 5- to 7-membered heterocyclic alkyl containing one or two heteroatoms selected from O and N. In some embodiments of the compounds of formula (V), ring A is a 6-membered heterocyclic alkyl containing one heteroatom that is O.

[0295] In some embodiments of the compound of formula (V), each R 15e Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 ).

[0296] In some embodiments of the compound of formula (V), each R 15e Independently halogenated, oxo-, -CN, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups.

[0297] In some embodiments of the compound of formula (V), each R 15e Independently halogen, oxo, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups.

[0298] In some embodiments of the compound of formula (V), the two R on adjacent carbons 15e They link together to form C2 subene groups.

[0299] In some embodiments of the compound of formula (V), the two R atoms on the same atom 15e Connected together to form C 3-6 cycloalkyl or C 2-9 Heterocyclic alkyl groups; each optionally substituted by one, two, or three independently selected from the following groups: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 and -N(R) 10 (R) 11 ).

[0300] In some embodiments of the compound of formula (V), the two R atoms on the same atom 15e Connected together to form C 3-6 Cycloalkyl groups, optionally substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 and -N(R) 10 (R) 11 ).

[0301] In some embodiments of the compound of formula (V), the two R atoms on the same atom 15e Connected together to form C 3-6 Cycloalkyl.

[0302] In some embodiments of the compound of formula (V), the two R atoms on different atoms 15e Connected together to form C 3-6 cycloalkyl or C 2-9 Heterocyclic alkyl groups; each optionally substituted by one, two, or three independently selected from the following groups: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 and -N(R) 10 (R) 11 ).

[0303] In some embodiments of the compound of formula (V), the two R atoms on different atoms 15e Connected together to form C 3-6 Cycloalkyl groups, optionally substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 and -N(R) 10 (R) 11 ).

[0304] In some embodiments of the compound of formula (V), the two R atoms on different atoms 15e Connected together to form C 3-6 Cycloalkyl.

[0305] In some embodiments of the compounds of formula (V), n is 0 to 4. In some embodiments of the compounds of formula (V), n is 2 to 4. In some embodiments of the compounds of formula (V), n is 2. In some embodiments of the compounds of formula (V), n is 1 or 2. In some embodiments of the compounds of formula (V), n is 1. In some embodiments of the compounds of formula (V), n is 1 to 3.

[0306] In some embodiments of the compound of formula (V), for .

[0307] In some embodiments of the compound of formula (V), Z 1 For N. In some embodiments of the compound of formula (V), Z 1 For CR 1b .

[0308] In some embodiments of the compound of formula (V), R 1b It is hydrogen or halogen. In some embodiments of the compound of formula (V), R 1b It is hydrogen.

[0309] In some embodiments of the compound of formula (V), X is -C(R) 6 (R) 6a X is -, -S-, or -O-. In some embodiments of compounds of formula (V), X is -C(R)-, -S-, or -O-. 6 (R) 6a X is - or -O-. In some embodiments of compounds of formula (V), X is -C(R)- or -O-. 6 (R) 6a In some embodiments of the compounds of formula (V), X is -O-. In some embodiments of the compounds of formula (V), X is -S-. In some embodiments of the compounds of formula (V), X is -N(R)-. 7 In some embodiments of compounds of formula (V), X is -S-, -O-, or -N(R). 7 )-.

[0310] In some embodiments of the compound of formula (V), R 6 and R 6a Independently hydrogen, halogen, C 1-6 Alkyl or C 1-6Halogenated alkyl group. In some embodiments of compounds of formula (V), R 6 and R 6a Independently hydrogen or C 1-6 Alkyl group. In some embodiments of compounds of formula (V), R 6 and R 6a For hydrogen. In some embodiments of the compound of formula (V), R 6 With R 6a They link together to form oxygen.

[0311] In some embodiments of the compound of formula (V), R 7 For hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl group. In some embodiments of compounds of formula (V), R 7 It is hydrogen or C 1-6 Alkyl group. In some embodiments of compounds of formula (V), R 7 It is hydrogen.

[0312] In some embodiments of the compound of formula (V), R 1 C 6-10 Aryl or C 1-9 heteroaryl; each optionally selected from one, two or three of R 15a Substitution of groups.

[0313] In some embodiments of the compound of formula (V), R 1 C 1-9 heteroaryl groups, which may optionally be selected from one, two or three R groups. 15a Substitution of groups.

[0314] In some embodiments of the compound of formula (V), R 1 It is a 5- or 6-membered heteroaryl group, which is optionally composed of one, two, or three groups selected from R. 15a Substitution of groups.

[0315] In some embodiments of the compound of formula (V), R 1 It is a 5-membered heteroaryl group, which is optionally composed of one, two, or three components selected from R. 15a Substitution of groups.

[0316] In some embodiments of the compound of formula (V) or its pharmaceutically acceptable salt or solvation, R 1 C is arbitrarily replaced 1-9 Heteroaryl. In some embodiments of compounds of formula (V) or their pharmaceutically acceptable salts or solvates, R 1The substituted 5- or 6-membered heteroaryl group. In some embodiments of compounds of formula (V) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5-membered heteroaryl group. In some embodiments of compounds of formula (V) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 6-membered heteroaryl group. In some embodiments of compounds of formula (V) or their pharmaceutically acceptable salts or solvates, R 1 It is a monocyclic heteroaryl group. In some embodiments of compounds of formula (V) or their pharmaceutically acceptable salts or solvates, R 1 It is a bicyclic heteroaryl group. In some embodiments, R 1 Optionally selected by one, two or three from R 15a The group is substituted. In some embodiments, R 1 Optionally selected by one, two or three halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and C 1-6 Alkyl group substitution. In some embodiments, R 1 Optionally, it is selected from one, two, or three groups: oxo, -CN, amino, OH, halogen, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy and C 3-6 Cycloalkyl groups are substituted.

[0317] In some embodiments of the compound of formula (V) or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are optionally selected by one, two, or three of R... 15a The group is substituted. In some embodiments of compounds of formula (IV) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The group is substituted. In some embodiments of compounds of formula (V) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The groups are substituted and each R 15a Independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (V) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, are selected from R 15a The group is substituted and R 15a Selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 .

[0318] In some embodiments of the compound of formula (V), R 1 C is selected from pyrazolyl and thiazolyl groups. 1-9 Heteroaryl groups, wherein the pyrazolyl and thiazolyl groups are optionally selected from R by one, two, or three of them. 15a Substitution of groups.

[0319] In some embodiments of the compound of formula (V), R 1 It is a thiazolyl group, which is optionally surrounded by one, two, or three groups selected from R. 15a Substitution of groups.

[0320] In some embodiments of the compound of formula (V), R 1 It is a pyrazolyl group, which is optionally surrounded by one, two or three groups selected from R. 15a Substitution of groups.

[0321] In some embodiments of the compound of formula (V), R 1 for In some embodiments of the compound of formula (V), R 1 for .

[0322] In some embodiments of the compound of formula (V), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (V), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (V), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (V), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 .

[0323] In some embodiments of the compound of formula (V), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15a Each R 15b and each R15c Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15a Each R 15b and each R 15c Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15a Each R 15b and each R 15c Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15a Each R 15b and each R 15c Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15a Each R 15b and each R 15c Independently for -OR 10 .

[0324] In some embodiments of the compound of formula (V), each R 15a Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11In some embodiments of the compounds of formula (V), each R 15a Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (V), each R 15a Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (V), each R 15a Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15a Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15a Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15a Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15a Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15a Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15a Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15a Independently for -OR 10 .

[0325] In some embodiments of the compound of formula (V), each R15b Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (V), each R 15b Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (V), each R 15b Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (V), each R 15b Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 .

[0326] In some embodiments of the compound of formula (V), each R 15b Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15b Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15bIndependent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15b Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15b Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15b Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15b Independently for -OR 10 .

[0327] In some embodiments of the compound of formula (V), each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (V), each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (V), each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10(R) 11 In some embodiments of the compounds of formula (V), each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 .

[0328] In some embodiments of the compound of formula (V), each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15c Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15c Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15c Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15c Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15c Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compound of formula (V), each R 15c Independently for -OR 10 .

[0329] This document also discloses a compound of formula (VI) or a pharmaceutically acceptable salt or solvate thereof: , in: R 2 C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 heteroaryl; each optionally selected from one, two, three or four R 15c Substitution of groups; Z 1 For CR 1b Or N; R1 C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 heteroaryl; each optionally selected from one, two or three of R 15a Substitution of groups; R 1b For hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -SF5, -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 or -CH2S(O)2N(R) 10 (R) 11 ), where C1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two or three of R... 15b Substitution of groups; X is -C(R) 6 (R) 6a -, -S-, -O-, or -N(R) 7 )-; R 6 and R 6a Independently hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R)11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 or -CH2S(O)2N(R) 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; or R 6 With R 6a They link together to form oxygen; R 7 Selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Ring B is C 3-6 cycloalkyl, C 6-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 Mixed aromatics; Each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 or -CH2S(O)2N(R) 10 (R) 11), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -CH2-C 3-10 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 heteroaryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R10 (R) 11 ); Each R 15e Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 or -CH2S(O)2N(R) 10 (R) 11), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -CH2-C 3-10 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 heteroaryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R10 (R) 11 ); Or two R on adjacent carbons 15e They link together to form C2 subene groups; Or two R atoms on the same atom 15e Connected together to form C 3-6 cycloalkyl or C 2-9 Heterocyclic alkyl groups; each optionally substituted by one, two, or three independently selected from the following groups: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ); Or two R on different atoms 15eConnected together to form C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 Heteroaryl groups; each optionally substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(O)(NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ); n is between 0 and 6; Each R 10 For hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 11 For hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups; Each R 12 For hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups; and Each R 13 For hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatic compounds.

[0330] In some embodiments of the compound of formula (VI), R 2 C 6-10Aryl or C 1-9 heteroaryl; each optionally selected from one, two, three or four R 15c Substitution of groups.

[0331] In some embodiments of the compound of formula (VI), R 2 C 1-9 heteroaryl groups, which may optionally be selected from one, two, three or four R groups. 15c Substitution of groups.

[0332] In some embodiments of the compound of formula (VI), R 2 It is a 5- or 6-membered heteroaryl group, which is optionally composed of one, two, three, or four groups selected from R. 15c Substitution of groups.

[0333] In some embodiments of the compound of formula (VI), R 2 It is a 6-membered heteroaryl group, which is optionally composed of one, two, three or four components selected from R. 15c Substitution of groups.

[0334] In some embodiments of the compound of formula (VI), R 2 It is a pyridinyl group, which is optionally surrounded by one, two, three or four groups selected from R. 15c Substitution of groups.

[0335] In some embodiments of the compound of formula (VI), R 2 It is a phenyl group, which is optionally composed of one, two, three or four radicals selected from R. 15c Substitution of groups.

[0336] In some embodiments of the compound of formula (VI), R 2 for .

[0337] In some embodiments of the compound of formula (VI), ring B is C. 6-9 Heterocyclic alkyl groups.

[0338] In some embodiments of the compound of formula (VI), each R 15e Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 ).

[0339] In some embodiments of the compound of formula (VI), each R 15e Independently halogenated, oxo-, -CN, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups.

[0340] In some embodiments of the compound of formula (VI), each R 15e Independently halogen, oxo, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups.

[0341] In some embodiments of the compound of formula (VI), the two R on adjacent carbons 15e They link together to form C2 subene groups.

[0342] In some embodiments of the compound of formula (VI), the two R atoms on the same atom 15e Connected together to form C 3-6 cycloalkyl or C 2-9 Heterocyclic alkyl groups; each optionally substituted by one, two, or three independently selected from the following groups: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 and -N(R) 10 (R) 11 ).

[0343] In some embodiments of the compound of formula (VI), the two R atoms on the same atom 15e Connected together to form C 3-6 Cycloalkyl groups, optionally substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 and -N(R) 10 (R) 11 ).

[0344] In some embodiments of the compound of formula (VI), the two R atoms on the same atom 15e Connected together to form C 3-6 Cycloalkyl.

[0345] In some embodiments of the compound of formula (VI), the two R atoms on different atoms 15e Connected together to form C 3-6 cycloalkyl or C 2-9 Heterocyclic alkyl groups; each optionally substituted by one, two, or three independently selected from the following groups: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 and -N(R) 10 (R) 11 ).

[0346] In some embodiments of the compound of formula (VI), the two R atoms on different atoms 15e Connected together to form C 3-6 Cycloalkyl groups, optionally substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 and -N(R) 10 (R) 11 ).

[0347] In some embodiments of the compound of formula (VI), the two R atoms on different atoms 15e Connected together to form C 3-6 Cycloalkyl.

[0348] In some embodiments of the compounds of formula (VI), n is 0 to 4. In some embodiments of the compounds of formula (VI), n is 2 to 4. In some embodiments of the compounds of formula (VI), n is 2. In some embodiments of the compounds of formula (VI), n is 1 or 2. In some embodiments of the compounds of formula (VI), n is 1. In some embodiments of the compounds of formula (VI), n is 1 to 3.

[0349] In some embodiments of the compound of formula (VI), for .

[0350] In some embodiments of the compound of formula (VI), Z 1For N. In some embodiments of the compound of formula (VI), Z 1 For CR 1b .

[0351] In some embodiments of the compound of formula (VI), R 1b It is hydrogen or halogen. In some embodiments of the compounds of formula (VI), R 1b It is hydrogen.

[0352] In some embodiments of the compound of formula (VI), X is -C(R) 6 (R) 6a -, -S-, or -O-. In some embodiments of compounds of formula (VI), X is -C(R)-, -S-, or -O-. 6 (R) 6a X is - or -O-. In some embodiments of compounds of formula (VI), X is -C(R)- or -O-. 6 (R) 6a In some embodiments of the compounds of formula (VI), X is -O-. In some embodiments of the compounds of formula (VI), X is -S-. In some embodiments of the compounds of formula (VI), X is -N(R)-. 7 In some embodiments of compounds of formula (VI), X is -S-, -O-, or -N(R). 7 )-.

[0353] In some embodiments of the compound of formula (VI), R 6 and R 6a Independently hydrogen, halogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl. In some embodiments of compounds of formula (VI), R 6 and R 6a Independently hydrogen or C 1-6 Alkyl group. In some embodiments of compounds of formula (VI), R 6 and R 6a For hydrogen. In some embodiments of the compound of formula (VI), R 6 With R 6a They link together to form oxygen.

[0354] In some embodiments of the compound of formula (VI), R 7 For hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl. In some embodiments of compounds of formula (VI), R 7 It is hydrogen or C 1-6 Alkyl group. In some embodiments of compounds of formula (VI), R 7 It is hydrogen.

[0355] In some embodiments of the compound of formula (VI), R 1 C 6-10 Aryl or C 1-9 heteroaryl; each optionally selected from one, two or three of R 15a Substitution of groups.

[0356] In some embodiments of the compound of formula (VI), R 1 C 1-9 heteroaryl groups, which may optionally be selected from one, two or three R groups. 15a Substitution of groups.

[0357] In some embodiments of the compound of formula (VI), R 1 It is a 5- or 6-membered heteroaryl group, which is optionally composed of one, two, or three groups selected from R. 15a Substitution of groups.

[0358] In some embodiments of the compound of formula (VI), R 1 It is a 5-membered heteroaryl group, which is optionally composed of one, two, or three components selected from R. 15a Substitution of groups.

[0359] In some embodiments of the compound of formula (VI) or its pharmaceutically acceptable salt or solvation, R 1 C is arbitrarily replaced 1-9 heteroaryl. In some embodiments of compounds of formula (VI) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5- or 6-membered heteroaryl group. In some embodiments of compounds of formula (VI) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 5-membered heteroaryl group. In some embodiments of compounds of formula (VI) or their pharmaceutically acceptable salts or solvates, R 1 The substituted 6-membered heteroaryl group. In some embodiments of compounds of formula (VI) or their pharmaceutically acceptable salts or solvates, R 1 It is a monocyclic heteroaryl group. In some embodiments of compounds of formula (VI) or their pharmaceutically acceptable salts or solvates, R 1 It is a bicyclic heteroaryl group. In some embodiments, R 1 Optionally selected by one, two or three from R 15a The group is substituted. In some embodiments, R 1 Optionally selected by one, two or three halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and C 1-6 Alkyl group substitution. In some embodiments, R1 Optionally, it is selected from one, two, or three groups: oxo, -CN, amino, OH, halogen, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy and C 3-6 Cycloalkyl groups are substituted.

[0360] In some embodiments of the compound of formula (VI) or its pharmaceutically acceptable salt or solvation, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are optionally selected by one, two, or three of R... 15a The group substitution. In some embodiments of compounds of formula (VI) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The group substitution. In some embodiments of compounds of formula (VI) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 The heteroaryl group is selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, wherein one, two, or three of the pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl groups are selected from R. 15a The groups are substituted and each R 15a Independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 In some embodiments of compounds of formula (VI) or their pharmaceutically acceptable salts or solvates, R 1 C 1-9 Heteroaryl groups, selected from pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrimidinyl, pyridazinyl, and pyridinyl, are selected from R 15a The group is substituted and R 15a Selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 10 .

[0361] In some embodiments of the compound of formula (VI), R 1 C is selected from pyrazolyl and thiazolyl groups. 1-9 Heteroaryl groups, wherein the pyrazolyl and thiazolyl groups are optionally selected from R by one, two, or three of them. 15a Substitution of groups.

[0362] In some embodiments of the compound of formula (VI), R 1 It is a thiazolyl group, which is optionally surrounded by one, two, or three groups selected from R. 15a Substitution of groups.

[0363] In some embodiments of the compound of formula (VI), R 1 It is a pyrazolyl group, which is optionally surrounded by one, two or three groups selected from R. 15a Substitution of groups.

[0364] In some embodiments of the compound of formula (VI), R 1 for In some embodiments of the compound of formula (VI), R 1 for .

[0365] In some embodiments of the compound of formula (VI), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (VI), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (VI), each R 15a Each R 15b and each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (VI), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 .

[0366] In some embodiments of the compound of formula (VI), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15a Each R 15b and each R 15c Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15a Each R 15b and each R 15c Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15a Each R 15b and each R 15c Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15aEach R 15b and each R 15c Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15a Each R 15b and each R 15c Independently for -OR 10 .

[0367] In some embodiments of the compound of formula (VI), each R 15a Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (VI), each R 15a Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (VI), each R 15a Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (VI), each R 15a Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15aIndependent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15a Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15a Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15a Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15a Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15a Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15a Independently for -OR 10 .

[0368] In some embodiments of the compound of formula (VI), each R 15b Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (VI), each R 15b Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (VI), each R 15b Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (VI), each R 15b Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 .

[0369] In some embodiments of the compound of formula (VI), each R 15b Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15b Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15b Independent of halogen, C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15b Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15b Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15b Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15b Independently for -OR 10 .

[0370] In some embodiments of the compound of formula (VI), each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C1-6 Haloalkyl, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -N(R) 10 (R) 11 -C(O)OR 10 -C(O)R 13 or -C(O)N(R) 10 (R) 11 In some embodiments of the compounds of formula (VI), each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (VI), each R 15c Independently halogenated, oxo-, -CN, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, -OR 10 or -N(R) 10 (R) 11 In some embodiments of the compounds of formula (VI), each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl or -OR 10 .

[0371] In some embodiments of the compound of formula (VI), each R 15c Independent of halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15c Independent of halogen, C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15c Independent of halogen, C 1-6 Alkyl or -OR 10In some embodiments of the compounds of formula (VI), each R 15c Independently for C 1-6 Alkyl, C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15c Independently for C 1-6 Alkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15c Independently for C 3-10 cycloalkyl or -OR 10 In some embodiments of the compounds of formula (VI), each R 15c Independently for -OR 10 .

[0372] In some embodiments of compounds of formula (IV), (V), or (VI), each R 10 Independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 heteroaryl, of which C 1-6 Alkyl, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Heteroaryl. In some embodiments of compounds of formula (IV), (V), or (VI), each R 10 Independently hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, wherein C 1-6 Alkyl, C 3-6 cycloalkyl and C 2-9 The heterocyclic alkyl group is optionally substituted with one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Heteroaryl. In some embodiments of compounds of formula (IV), (V), or (VI), each R 10 Independently hydrogen, C 1-6 Alkyl or C 1-6 Haloalkyl, wherein C 1-6 The alkyl group is optionally substituted with one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Heteroaryl. In some embodiments of compounds of formula (IV), (V), or (VI), each R 10 Independently hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups. In some embodiments of compounds of formula (IV), (V), or (VI), each R... 10 Independently for C 1-6 Alkyl or C 1-6 Halogenated alkyl groups. In some embodiments of compounds of formula (IV), (V), or (VI), each R... 10 Independently for C 1-6 Alkyl. In some embodiments of compounds of formula (IV), (V), or (VI), each R 10 Methyl. In some embodiments of compounds of formula (IV), (V), or (VI), each R... 10 Independently for C 1-6 Halogenated alkyl groups.

[0373] In some embodiments of compounds of formula (IV), (V), or (VI), each R 11 Independently hydrogen or C 1-6 Alkyl. In some embodiments of compounds of formula (IV), (V), or (VI), each R 11 Independently hydrogen. In some embodiments of compounds of formula (IV), (V), or (VI), each R... 11 Independently for C 1-6 Alkyl. In some embodiments of compounds of formula (IV), (V), or (VI), each R 12 Independently hydrogen, C 1-6 Alkyl or C 1-6 Halogenated alkyl groups. In some embodiments of compounds of formula (IV), (V), or (VI), each R... 12Independently hydrogen or C 1-6 Alkyl. In some embodiments of compounds of formula (IV), (V), or (VI), each R 12 Independently hydrogen. In some embodiments of compounds of formula (IV), (V), or (VI), each R... 12 Independently for C 1-6 alkyl.

[0374] In some embodiments of compounds of formula (IV), (V), or (VI), each R 13 Independently hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Heteroaryl. In some embodiments of compounds of formula (IV), (V), or (VI), each R 13 Independently hydrogen, C 1-6 Alkyl, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl or C 1-9 heteroaryl, of which C 1-6 Alkyl, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9Heteroaryl. In some embodiments of compounds of formula (IV), (V), or (VI), each R 13 Independently hydrogen, C 1-6 Alkyl, C 3-6 cycloalkyl or C 2-9 Heterocyclic alkyl, wherein C 1-6 Alkyl, C 3-6 cycloalkyl and C 2-9 The heterocyclic alkyl group is optionally substituted with one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Heteroaryl. In some embodiments of compounds of formula (IV), (V), or (VI), each R 13 Independently hydrogen, C 1-6 Alkyl groups, optionally substituted with one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Heteroaryl. In some embodiments of compounds of formula (IV), (V), or (VI), each R 13 Independently hydrogen or C 1-6 Alkyl. In some embodiments of compounds of formula (IV), (V), or (VI), each R 13 Independently for C 1-6 alkyl.

[0375] This document covers any combination of groups described above with respect to various variables. Throughout the specification, those skilled in the art select groups and their substituents to provide stable moieties and compounds.

[0376] In some embodiments, a compound or a pharmaceutically acceptable salt or solvate thereof is described herein, wherein the compound is selected from the compounds in Table 1B: Table 1B. Exemplary Compounds

[0377]

[0378] In some embodiments, a compound or a pharmaceutically acceptable salt or solvate thereof is described herein, wherein the compound is selected from the compounds in Table 1C: Table 1C. Exemplary Compounds

[0379] Other forms of the compounds disclosed herein Isomers / stereoisomers In some embodiments, the compounds described herein exist as geometric isomers. In some embodiments, the compounds described herein have one or more double bonds. The compounds presented herein include all cis, trans, syn, anti, isolateral (E), and isolateral (Z) isomers and their corresponding mixtures. In some cases, the compounds described herein have one or more chiral centers, each center being in an R or S configuration. The compounds described herein include all diastereomeric, enantiomeric, and epimeric forms and their corresponding mixtures. In additional embodiments of the compounds and methods provided herein, mixtures of enantiomers and / or diastereomeric compounds resulting from a single preparation step, combination, or interconversion are suitable for the applications described herein. In some embodiments, the compounds described herein are prepared in their individual stereoisomer forms as follows: a racemic mixture of the compounds is reacted with an optically active resolving agent to form diastereomeric compound pairs, the diastereomeric compounds are separated, and the optically pure enantiomers are recovered. In some embodiments, a dissociable complex is preferred. In some embodiments, the diastereomers have different physical properties (e.g., melting point, boiling point, solubility, reactivity, etc.) and are separated using these dissimilarity properties. In some embodiments, the diastereomers are separated by chiral chromatography or preferably by separation / resolution techniques based on differences in solubility. In some embodiments, the optically pure enantiomers and the resolving agent are subsequently recovered by any practical means that will not cause racemization.

[0380] Labeled compounds In some embodiments, the compounds described herein are present in their isotopically labeled form. In some embodiments, the methods disclosed herein include methods of treating a disease by administering such isotopically labeled compounds. In some embodiments, the methods disclosed herein include methods of treating a disease by administering such isotopically labeled compounds in the form of pharmaceutical compositions. Thus, in some embodiments, the compounds disclosed herein include isotopically labeled compounds that are identical to the compounds listed herein, except that one or more atoms have undergone atomic substitutions with atomic masses or mass numbers different from those normally found in nature. Examples of isotopes that may be incorporated into the compounds disclosed herein include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, such as... 2 H (D), 3 H, 13 C 14 C 15 N、 18 O、 17 O、 31 P, 32 P, 35 S, 18 F and 36 Cl. Other isotopes of the compounds described herein, containing the aforementioned isotopes and / or other atoms, and their pharmaceutically acceptable salts, solvates, or stereoisomers, are within the scope of this disclosure. Certain isotopically labeled compounds (e.g., and having such...) 3 H and 14 Those compounds containing radioactive isotopes of C can be used in drug and / or substrate tissue distribution assays. Tritium isotopes (i.e., 3 H) and carbon-14 isotopes (i.e., ... 14 C) is particularly preferred due to its ease of preparation and detectability. In some embodiments, the compounds described herein can be artificially enriched in one or more isotopes not abundantly found in nature. In some embodiments, the compounds described herein can be artificially enriched in one or more isotopes selected from deuterium (… 2 H), tritium ( 3 H), Iodine-125 ( 125 I) or carbon-14 ( 14 In some embodiments, the compounds described herein are artificially enriched in one or more isotopes selected from: 2 H, 11 C 13 C 14 C 15 C 12 N、 13 N、 15 N、 16 N、16 O、 17 O、 14 F, 15 F, 16 F, 17 F, 18 F, 33 S, 34 S, 35 S, 36 S, 35 Cl、 37 Cl、 79 Br、 81 Br、 131 I and 125 I. In some embodiments, the abundance of the enriched isotope is independently at least 1 mol%, at least 10 mol%, at least 20 mol%, at least 30 mol%, at least 40 mol%, at least 50 mol%, at least 60 mol%, at least 70 mol%, at least 80 mol%, at least 90 mol%, or 100 mol%.

[0381] In some embodiments, the deuterium abundance in each of the substituents disclosed herein is independently at least 1 mol%, at least 10 mol%, at least 20 mol%, at least 30 mol%, at least 40 mol%, at least 50 mol%, at least 60 mol%, at least 70 mol%, at least 80 mol%, at least 90 mol%, or 100 mol%. In some embodiments, one or more of the substituents disclosed herein contain a percentage of deuterium higher than the native abundance of deuterium. In some embodiments, one or more of the substituents disclosed herein... 1 H is replaced by one or more deuterium atoms.

[0382] In some embodiments, the compounds described herein are labeled by other means, including but not limited to the use of chromophores or fluorescent moieties, bioluminescent labeling, or chemiluminescent labeling.

[0383] Pharmaceutically acceptable salts In some embodiments, the compounds described herein are present in their pharmaceutically acceptable salt form. In some embodiments, the methods disclosed herein include methods of treating a disease by administering such pharmaceutically acceptable salts. In some embodiments, the methods disclosed herein include methods of treating a disease by administering such pharmaceutically acceptable salts in the form of a pharmaceutical composition.

[0384] In some embodiments, the compounds described herein have acidic or basic groups and thus react with a variety of inorganic or organic bases and any of inorganic and organic acids to form pharmaceutically acceptable salts. In some embodiments, such salts are prepared in situ during the final isolation and purification of the compounds disclosed herein or their solvates or stereoisomers, or by reacting the purified compound in its free form with a suitable acid or base alone and isolating the resulting salt.

[0385] Examples of pharmaceutically acceptable salts include those prepared by reacting the compounds described herein with inorganic acids, organic acids, or inorganic bases. Such salts include acetates, acrylates, adipates, alginates, aspartates, benzoates, benzenesulfonates, hydrogen sulfates, bisulfites, bromides, butyrates, butyn-1,4-dicitates, camphorates, camphorsulfonates, hexanoates, octanoates, chlorobenzoates, chlorides, citrates, cyclopentanepropionates, decanoates, disglucose, dihydrogen phosphates, dinitrobenzoates, dodecyl sulfates, ethanesulfonates, formates, fumarates, glucoheptates, glycerophosphates, glycolic acid salts, hemisulfates, heptanates, hexyn-1,6-dicitates, hydroxybenzoates, and γ-hydroxybutyrates. Salts, hydrochlorides, hydrobromides, hydroiodates, 2-hydroxyethanesulfonates, iodides, isobutyrates, lactates, maleates, malonates, methanesulfonates, amygdalinates, metaphosphates, methanesulfonates, methoxybenzoates, methylbenzoates, monohydrogen phosphates, 1-naphthalenesulfonates, 2-naphthalenesulfonates, nicotinates, nitrates, palmitates, pectinates, persulfates, 3-phenylpropionates, phosphates, picrates, neopentanoates, propionates, pyrosulfates, pyrophosphates, propynates, phthalates, phenylacetates, phenylbutyrates, propanesulfonates, salicylates, succinates, sulfates, sulfites, succinates, octanoates, sebacic acid salts, sulfonates, tartrates, thiocyanates, toluenesulfonates, undecanoates, and xylenesulfonates.

[0386] Furthermore, the compounds described herein can be prepared as pharmaceutically acceptable salts by reacting the compounds in their free base form with a pharmaceutically acceptable inorganic or organic acid, including but not limited to: inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, metaphosphoric acid, and similar acids; and organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, p-toluenesulfonic acid, tartaric acid, trifluoroacetic acid, citric acid, etc. Benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, arylsulfonic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, 4-methylbicyclo-[2.2.2]oct-2-en-1-carboxylic acid, glucoheponic acid, 4,4'-methylenebis-(3-hydroxy-2-en-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, lauryl sulfate, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, and mucoconic acid. In some embodiments, other acids, such as oxalic acid, although pharmaceutically unacceptable on their own, are used to prepare salts suitable as intermediates for obtaining the compounds disclosed herein, their solvates or stereoisomers, and their pharmaceutically acceptable acid addition salts.

[0387] In some embodiments, the compounds described herein containing free acid groups react with a suitable base (such as hydroxides, carbonates, bicarbonates, and sulfates of pharmaceutically acceptable metal cations), ammonia, or a pharmaceutically acceptable primary, secondary, tertiary, or quaternary organic amine. Representative salts include alkali metal or alkaline earth metal salts, such as lithium, sodium, potassium, calcium, and magnesium sa...

Claims

1. A method of treating cancer in a subject of need, the method comprising administering to the subject: (a) Compounds of formula (I) or their pharmaceutically acceptable salts: ； in: Y 1 For CR 1a Or N; Y 2 For CR 2a Or N; Y 3 For CR 3a Or N; Y 4 For CR 4a Or N; Y 5 For CR 5a Or N; Z 1 For CR 1b Or N; Z 2 For CR 2b Or N; Z 3 For CR 3b Or N; where Y 1 Y 2 Y 3 Y 4 Y 5 Z 1 Z 2 and Z 3 At least one of them is N; X is selected from -C(R) 6 (R) 6a -, -O- and -N(R) 7 )-; R 1 C 1-9 heteroaryl groups, which may optionally be selected from one, two or three R groups. 15a Substitution of groups; R 1a R 2a R 3a R 4a R 5a R 1b R 2b and R 3b Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -SF5, -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally selected by one, two or three of R... 15b Substitution of groups; R 6 and R 6a Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl, C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; R 7 Selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 10 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 Mixed aromatics; Each R 11 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 12 Independently selected from hydrogen and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups; Each R 13 Selected independently from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three groups selected from the following: halogen, -CN, hydroxyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, C 6-10 Aryl and C 1-9 heteroaryl; and Each R 15a and each R 15b Each is independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, -CH2-C 3-6 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, C 1-9 heteroaryl, -CH2-C 1-9 Mixed aromatics, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -CH2-C 3-10 cycloalkyl, C 2-9 Heterocyclic alkyl, -CH2-C 2-9 Heterocyclic alkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 heteroaryl and C 1-9 The heteroaryl group may optionally be substituted by one, two, or three independently selected groups from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 10 -SR 10 -N(R) 10 (R) 11 -C(O)OR 10 -OC(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)N(R 10 (R) 11 ), -N(R 12 )C(O)OR 13 -N(R) 12 )S(O)2R 13 -C(O)R 13 -S(O)R 13 -OC(O)R 13 -C(O)N(R) 10 (R) 11 -C(O)C(O)N(R) 10 (R) 11 ), -N(R 12 )C(O)R 13 -S(O)2R 13 -S(O)2N(R) 10 (R) 11 )-、S(=O)(=NH)N(R 10 (R) 11 -CH2C(O)N(R) 10 (R) 11 ), -CH2N(R 12 )C(O)R 13 -CH2S(O)2R 13 and -CH2S(O)2N(R 10 (R) 11 ); (b) An additional agent, wherein the additional agent is an anticancer agent. The combination of the compound of formula (I) or its pharmaceutically acceptable salt and the additional agent is therapeutically effective for treating the cancer.

2. A method of treating cancer in a subject of need, the method comprising administering to the subject: (a) 2,4-Dimethoxy-N-(4-methoxy-6-(thiazolyl-2-yloxy)benzo[d]isoxazol-3-yl)-6-methylpyridine-3-sulfonamide (Compound 57), or a pharmaceutically acceptable salt thereof; and (b) An additional agent, wherein the additional agent is an anticancer agent.

3. The method of claim 2, wherein the combination of compound 57 or a pharmaceutically acceptable salt thereof and the additional agent is therapeutically effective.

4. The method according to any one of claims 1 to 3, wherein the cancer is lung cancer, mesothelioma, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, melanoma of the skin or eye, multiple myeloma, uterine cancer, ovarian cancer, rectal cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer (CRC), breast cancer, endometrial cancer, cervical cancer, vaginal cancer, Hodgkin's disease, esophageal cancer, small bowel cancer, endocrine system cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, hematologic malignancies, chronic or acute leukemia, lymphocytic lymphoma, bladder cancer, kidney or ureter cancer, renal cell carcinoma, renal pelvis cancer, central nervous system (CNS) tumors, primary CNS lymphoma, spinal axis tumors, glioblastoma, brainstem glioma, pituitary adenoma, or a combination of two or more of the aforementioned cancers.

5. The method of any one of claims 1 to 4, wherein the cancer is breast cancer.

6. The method of claim 5, wherein the breast cancer is HR+ / HER2- breast cancer.

7. The method of claim 6, wherein the HR+ / HER2- breast cancer is ER+ / HER2- breast cancer.

8. The method of claim 7, wherein the ER+ / HER2- breast cancer is ER+ / KAT6a. 高 Breast cancer.

9. The method of any one of claims 6 to 8, wherein the HR+ / HER2- breast cancer, ER+ / HER2- breast cancer, or ER+ / KAT6a 高 Breast cancer can become resistant to endocrine therapy or chemotherapy.

10. The method of claim 9, wherein the breast cancer is resistant to endocrine therapy, and optionally the subject has been treated with endocrine therapy.

11. The method of claim 10, wherein the endocrine therapy comprises SERM, SERD, aromatase inhibitors, or CDK inhibitors.

12. The method of any one of claims 5 to 11, wherein the breast cancer is characterized by TP53 mutation, ESR1 mutation, Rb loss of function and / or CCNE amplification.

13. The method of claim 12, wherein the ESR1 mutation includes L536Q, Y537N, Y537S, D538G and / or E380Q.

14. The method of claim 9, wherein the breast cancer is resistant to chemotherapy, and optionally the subject has been treated with chemotherapy.

15. The method of claim 14, wherein the chemotherapy is epirubicin, doxorubicin, cyclophosphamide, docetaxel, paclitaxel, carboplatin, gemcitabine, lobaplatin, albumin-bound paclitaxel, cisplatin, or capecitabine.

16. The method of claim 11, wherein the CDK inhibitor comprises a CDK2 selective inhibitor, a CDK4 selective inhibitor, a CDK2 / 4 / 6 selective inhibitor, or a CDK4 / 6 selective inhibitor.

17. The method of claim 11, wherein the CDK inhibitor comprises a CDK4 / 6 selective inhibitor.

18. The method of claim 16 or 17, wherein the CDK inhibitor is PF-07220060, avozidil, AT7519, JNJ-7706621, PHA-793887, BMS-265246, mircizoli (PHA-848125), R547, livexib (P276-00), MC180295, G1T38, ON123300, purvalanol A, SU9516, ribociclib (LEE011), or BSJ-03-123, palbociclib, abecilib, or dalcilib, or a pharmaceutically acceptable salt thereof.

19. The method of any one of claims 1 to 4, wherein the cancer is NSCLC, small cell lung cancer (SCLC), triple-negative breast cancer (TNBC), or ER+ / KAT6a. 高 Breast cancer, melanoma, colorectal cancer (CRC), hepatocellular carcinoma (HCC), pancreatic cancer, ovarian cancer.

20. The method of claim 17, wherein the cancer is NSCLC with EGFR gene aberration, and the NSCLC is optionally resistant to treatment with an EGFR inhibitor, the EGFR inhibitor including afatinib, dacomitinib, erlotinib, gefitinib, osimertinib, ametinib, and / or vormetinib.

21. The method of claim 20, wherein the EGFR gene aberration is an exon 19 deletion (19del) or a missense mutation including L858R, T790M and / or C797S.

22. The method of any one of claims 1 to 4, wherein the cancer is optionally a multiple myeloma with 1q21 amplification.

23. The method of any one of claims 1 to 4, wherein the cancer is acute myeloid leukemia (AML).

24. The method of any one of claims 1 to 4, wherein the cancer is metastatic castration-resistant prostate cancer (mCRPC) or prostate cancer.

25. The method of claim 24, wherein the metastatic castration-resistant prostate cancer (mCRPC) or prostate cancer is resistant to hormone therapy.

26. The method of claim 24, wherein the metastatic castration-resistant prostate cancer (mCRPC) or prostate cancer is resistant to ADT, androgen synthesis inhibitors such as abiraterone, ketoconazole and amylamide, or androgen receptor blockers such as first-generation drugs: flutamide, bicalutamide and nilumid, and second-generation drugs: enzalutamide, apalutamide and dalolutamide.

27. The method of any one of claims 1 to 26, wherein the additional agent comprises endocrine therapy, CDK inhibitor, PI3K-AKT-mTOR pathway inhibitor, androgen synthesis inhibitor, androgen receptor blocker, radiopharmaceutical, immunotherapy, chemotherapy, Bcl-2 inhibitor, Bcl-xL inhibitor, or any combination thereof.

28. The method of any one of claims 1 to 26, wherein the additional agent comprises endocrine therapy.

29. The method of claim 28, wherein the endocrine therapy comprises SERM, SERD, or aromatase inhibitors.

30. The method of claim 29, wherein the endocrine therapy comprises tamoxifen, raloxifene, fulvestrant, allavestrant, carmistran, essenstrant, goserelin, imlunestrant, giretran, or ARV-471, anastrozole, letrozole, exemestane, or a pharmaceutically acceptable salt thereof.

31. The method of claim 29, wherein the endocrine therapy comprises elastin.

32. The method of any one of claims 1 to 26, wherein the additional agent comprises a CDK inhibitor.

33. The method of claim 32, wherein the CDK inhibitor comprises a CDK2 selective inhibitor, a CDK4 selective inhibitor, a CDK2 / 4 / 6 selective inhibitor, or a CDK4 / 6 selective inhibitor.

34. The method of claim 33, wherein the CDK inhibitor is PF-07220060, avozidil, AT7519, JNJ-7706621, PHA-793887, BMS-265246, mircizoli (PHA-848125), R547, livexib (P276-00), MC180295, G1T38, ON123300, purvalanol A, SU9516, ribociclib (LEE011), or BSJ-03-123, palbociclib, abecilib, or dalcilib, or a pharmaceutically acceptable salt thereof.

35. The method of any one of claims 1 to 24, wherein the additional agent comprises a PI3K-AKT-mTOR pathway inhibitor.

36. The method of claim 35, wherein the PI3K-AKT-mTOR pathway inhibitor comprises apelelix, rapamycin or a derivative thereof, sirolimus, everolimus, AZD8055, tamsulosin (CCI-779), PI-103, KU-0063794, torkinib (PP242), deforolimus (MK-8669), salpaselti (MLN0128), vortalisib (XL765), torin 1, torin 2, omepaliximab (GSK2126458), OSI-027, PF-04691502, apitolisib (GDC-0980), GSK1059615, gedatolisib (PKI-587), WYE-354, vitusertib (AZD2014), WYE-125132 (WYE-132), PP121, WYE-687, WAY-600, ETP-46464, GDC-0349, XL388, GNE-477, bimiralisib (PQR309), SF2523, CZ415, paxalisib (GDC-0084), CC-115, onatasertib (CC 223), zotamoxetine (ABT-578), tacrolimus (FK506), BGT226 maleate (NVP-BGT226 maleate), palomid 529 (P529), LY3023414 (samotolisib), biolimus-7, biolimus-9, azathioprine, campasyl 1H or rhubarb root acid, or pharmaceutically acceptable salts thereof.

37. The method of any one of claims 1 to 26, wherein the additional agent comprises hormone therapy.

38. The method of claim 37, wherein the additional agent is an androgen synthesis inhibitor.

39. The method of claim 38, wherein the androgen synthesis inhibitor is abiraterone, ketoconazole, aminoglutethimide, dutasteride, iristride, or α-estradiol, or a pharmaceutically acceptable salt thereof.

40. The method of any one of claims 1 to 26, wherein the additional agent is an androgen receptor blocker.

41. The method of claim 40, wherein the androgen receptor blocker is flutamide, bicalutamide, nilumet, enzalutamide, apalutamide, or dalolutamide, or a pharmaceutically acceptable salt thereof.

42. The method of any one of claims 1 to 26, wherein the additional agent is an immunotherapy.

43. The method of claim 42, wherein the immunotherapy is a PD-1 inhibitor, a PD-L1 inhibitor, a PD-L2 inhibitor, a CTLA-4 inhibitor, a LAG-3 inhibitor, a TIM-3 inhibitor, a T cell-activated V domain Ig inhibitor (VISTA) inhibitor, or a pharmaceutically acceptable salt thereof.

44. The method of claim 43, wherein the inhibitor is a small molecule, peptide, nucleotide, or antibody.

45. The method of claim 43, wherein the immunotherapy comprises nivolumab, pembrolizumab, pildizumab, AMP-224, PF-06801591, MEDI0680, PDR001, REGN2810, SHR-12-1, TSR-042, CA-170, atezolizumab, durvalumab, KN035, and BMS-936559, ipilimumab, trimemumab, AGEN1884, AGEN2041, BMS-986016, GSK2831781, IMP321, LAG525, MGD013 or TSR-022, or a pharmaceutically acceptable salt thereof.

46. ​​The method of any one of claims 1 to 26, wherein the additional agent comprises chemotherapy.

47. The method of claim 46, wherein the chemotherapy comprises azacitidine, decitabine, idarubicin, daunorubicin, cytarabine, pemetrexed, cisplatin, carboplatin, paclitaxel, albumin-bound paclitaxel, gemcitabine, etoposide, irinotecan, toponotecan, rubitidine, epirubicin, doxorubicin, liposomal doxorubicin, melphalan, bendamustine, thalidomide, lenalidomide, pomalidomide, bortezomib, celiniso, cyclophosphamide, docetaxel, lobaplatin, temozolomide, capecitabine, dacarbazine, 5-FU, carbazoxyl, mitoxantrone, or estradiol, or a pharmaceutically acceptable salt thereof.

48. The method of any one of claims 1 to 26, wherein the additional agent comprises a Bcl-2 inhibitor and / or a Bcl-xL inhibitor.

49. The method of claim 48, wherein the Bcl-2 inhibitor and / or Bcl-xL inhibitor comprises ABT-737, navittox (ABT-263), obacla (GX15-070), TW-37, venetox (ABT-199), AT101, HA14-1, sabutoclax, S55746, or APG-2575, or pharmaceutically acceptable salts thereof.

50. The method of any one of claims 1 to 26, wherein the additional agent comprises a radioactive agent.

51. A method of treating cancer in a subject of need, the method comprising administering to the subject: (a) 2,4-Dimethoxy-N-(4-methoxy-6-(thiazolyl-2-yloxy)benzo[d]isoxazol-3-yl)-6-methylpyridine-3-sulfonamide (Compound 57), or a pharmaceutically acceptable salt thereof; and (b) Ilasma group.

52. The method of claim 51, wherein the cancer is breast cancer.

53. The method of claim 52, wherein the breast cancer is HR+ / HER2- breast cancer.

54. The method of claim 53, wherein the HR+ / HER2- breast cancer is ER+ / HER2- breast cancer.

55. The method of claim 54, wherein the ER+ / HER2- breast cancer is ER+ / KAT6a. 高 Breast cancer.

56. The method of any one of claims 53 to 55, wherein the breast cancer is resistant to endocrine therapy or chemotherapy.

57. The method of claim 56, wherein the endocrine therapy comprises SERM, SERD, aromatase inhibitors, or CDK inhibitors.

58. The method of claim 57, wherein the CDK inhibitor comprises a CDK4 / 6 selective inhibitor.

59. The method of claim 57, wherein the CDK inhibitor is PF-07220060, avozidil, AT7519, JNJ-7706621, PHA-793887, BMS-265246, mircizoli (PHA-848125), R547, livexib (P276-00), MC180295, G1T38, ON123300, purvalanol A, SU9516, ribociclib (LEE011), or BSJ-03-123, palbociclib, abecilib, or dalcilib, or a pharmaceutically acceptable salt thereof.

60. The method of claim 56, wherein the chemotherapy is epirubicin, doxorubicin, cyclophosphamide, docetaxel, paclitaxel, carboplatin, gemcitabine, lobaplatin, albumin-bound paclitaxel, cisplatin, or capecitabine.

61. Use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating cancer, wherein the medicament is formulated for administration in combination with additional medicaments.

62. Use of a compound of formula (I) or a pharmaceutically acceptable salt thereof and additional agents in the manufacture of a medicament for treating cancer.

63. Use of a compound 57 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating cancer, wherein the medicament is formulated for use in combination with additional medicaments.

64. Use of a compound 57 or a pharmaceutically acceptable salt thereof and additional agents in the manufacture of a medicament for treating cancer.

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