Protein modulator, and pharmaceutical composition thereof, use thereof and method therefor

Abstract

The present invention belongs to the field of medicinal chemistry. Provided are a protein degrader, and a pharmaceutical composition thereof, the use thereof and a method therefor. Specifically provided are a compound represented by formula (I), or a stereoisomer, tautomer, polymorph, solvate, N-oxide, or isotopically labeled compound thereof, or a metabolite, or prodrug, or pharmaceutically acceptable salt or ester thereof. The compound of the present invention can be used for preventing and / or treating tumors.

Description

Protein modulators, their pharmaceutical compositions, and their uses and methods

[0001] This disclosure is based on and claims priority to Chinese patent applications No. 202411793342.3, filed on December 6, 2024; No. 202510067856.9, filed on January 16, 2025; No. 202510194560.3, filed on February 21, 2025; No. 202510713168.5, filed on May 29, 2025; and No. 202511168334.4, filed on August 20, 2025, the disclosures of which are incorporated herein by reference in their entirety. Technical Field

[0002] This invention belongs to the pharmaceutical field, specifically relating to protein modulators, their pharmaceutical compositions, preparation methods, and their uses and methods. Background Technology

[0003] The KEAP1-NRF2 (Kelch-like ECH-associated protein 1-nuclear factor E2-associated factor 2) pathway is involved in regulating various physiological functions such as oxidative stress, anti-inflammation, and detoxification, and is a major regulatory pathway in redox biology in mammalian cells. NRF2 (nuclear factor erythrocyte-2-associated factor 2), as a pleiotropic transcription factor, can be activated under the stimulation of oxidative stress, metabolic stress, and carcinogenic stress signals, inducing the expression of various downstream genes, thereby restoring cellular redox homeostasis. Pathological changes in NRF2 are widespread in various inflammatory diseases and cancers. KEAP1, as an upstream specific substrate adaptor protein of NRF2, can promote the formation of the NRF2-E3 ubiquitin ligase complex, thereby regulating the intracellular expression level of NRF2.

[0004] For tumor indications, investigational drugs targeting the KEAP1-NRF2 pathway mainly include NRF2 inhibitors / degraders and KEAP1 agonists. Research on treating tumors by regulating NRF2 expression levels through KEAP1 activation is still in the clinical exploration stage, with no clinical data released. Summary of the Invention

[0005] The present invention aims to provide a novel protein modulator compound, its pharmaceutical composition, preparation method, and its use and method in treating NRF2 dysregulation-related diseases such as tumors. The compound provided by the present invention exhibits high protein-binding activity and good anti-tumor activity, and can be used to regulate NRF2 expression levels by activating KEAP1.

[0006] On the one hand, the present invention provides a compound, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite, prodrug, or pharmaceutically acceptable salt or ester thereof, wherein the compound has a structure as shown in formula (I):

[0007] Among them, ring A is selected from 3-12 membered carbon rings, 3-12 membered heterocycles, and C. 6-10 Aromatic rings and 5-10 heterocyclic aromatic rings;

[0008] X 2 Selected from N and CR 3 ;

[0009] X 1 Selected from O, S (=O)2, -C (=C) 1-6 alkyl)-, -C(=C 1-6 (halogenated alkyl)-, CR 5 R 6 and NR 7 ;

[0010] R 1 Selected from C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, the C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Each alkynyl group is independently and optionally replaced by one or more substituents selected from H, deuterium, CN and halogens;

[0011] R 2 Each is independently selected from H, halogen, OH, C 1-6 Alkyl, C 2-6 alkenyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl groups and -C(=O)-(CH2) p -NR a R b The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl groups and -C(=O)-(CH2) p -NR a R bEach is independently and optionally influenced by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6- 10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR 5 R 6 Substituents are replaced by; and / or,

[0012] Two Rs 2 The atoms or R connected to it 2 R 7 The atoms connected to it together form C 3-10 Cycloalkyl, 3-12-membered heterocyclic or 5-10-membered heteroaryl, wherein the C 3-10 The cycloalkyl, 3-12-membered heterocyclic and 5-10-membered heteroaryl groups are each independently and optionally separated by one or more elements selected from halogen, H, OH, CN, -NR. 5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OC 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Substituents of aryl and 5-10 heteroaryl groups;

[0013] R 3 Selected from H, halogens, CN, OH, NO2, -NR 5 R 6 C1-6 Alkyl, C 1-6 Alkoxy, carboxyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, oxo groups, thio groups, C 3-10 cycloalkyl, -OC 3-10 Cycloalkyl and 3-12 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, carboxyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, oxo groups, thio groups, C 3-10 cycloalkyl, -OC 3-10 The cycloalkyl group and the 3-12 membered heterocyclic group are each independently and optionally surrounded by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl groups, -C(=O)-OH, NO2, and -NR 5 R 6 The substituents are replaced;

[0014] R 4 Selected from H, deuterium, halogen, oxo group, thio group, CN, OR 7 SR 7 S(=O)R 7 S(=O)2R 7 NO2, -NR 5 R 6 -NR 7 S(=O)2R c -S(=O)2N R 5 R 6 -C(=O)R7 -C(=O)OR 7 -C(=O)NR 5 R 6 -OC(=O)NR 5 R 6 -NR 7 C(=O)2R c -NR 7 C(=O)2NR 5 R 6 -NR 7 C(=O)2OR c C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl and 3-12 membered heterocyclic, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3-10 cycloalkyl, C 6-10 The aryl, 5-10 membered heteroaryl, and 3-12 membered heterocyclic groups are each independently and optionally bound by one or more groups selected from H, halogen, OH, CN, -COOH, oxo, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, C 1-6 Haloalkyl, C 1- 6-Haloalkoxy, -OC 3-10 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0015] Two Rs 4 The atoms connected to it together form C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more elements selected from H, halogen, OH, CN, -NR.5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OC 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Substituents of aryl and 5-10 heteroaryl groups;

[0016] R 5 R 6 and R 7 Each is independently selected from H, halogen, OH, CN, C 1-6 Alkyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-12 membered heterocyclic group, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-12 membered heterocyclic group, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR a R b -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR a R b The substituents are replaced;

[0017] Or, R 5 and R 6 The atoms connected to it together form C 3-10 Cycloalkyl or 3-12 membered heterocyclic groups, wherein the C 3- 10 The cycloalkyl group and the 3-12 membered heterocyclic group are each independently and optionally surrounded by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR a R b -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR a R b The substituents are replaced;

[0018] R a and R b Each is independently selected from H and C. 1-6 Alkyl, C 1-6 Alkoxy, C1-6 Haloalkyl, C 1-6 Heteroalkyl, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Heteroalkyl, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more elements selected from H, halogen, OH, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-10 Substituents of cycloalkyl groups;

[0019] R c Selected from H, OH, halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 1-6 Haloalkyl, C 1- 6-alkoxy, C 1-6 Halogenated alkoxy groups, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2- 6-alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1- 6-alkyl, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR 5 R 6 The substituents are replaced;

[0020] p is selected from 0, 1, 2, 3, 4, 5, and 6;

[0021] m and n are each independently selected from 0, 1, 2, 3 and 4.

[0022] Another aspect of the invention provides a therapeutic or pharmaceutical combination comprising the compound described herein, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite or prodrug or pharmaceutically acceptable salt or ester thereof, optionally further comprising one or more other therapeutic agents.

[0023] Another aspect of the present invention provides a pharmaceutical composition comprising a preventive or therapeutically effective amount of the compound of the present invention, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite or prodrug or pharmaceutically acceptable salt or ester thereof, and one or more pharmaceutically acceptable carriers.

[0024] Another aspect of the present invention provides the compounds described herein, or stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or metabolites or prodrugs or pharmaceutically acceptable salts or esters thereof, or therapeutic or pharmaceutical combinations described herein, or pharmaceutical compositions described herein, in preparation for the prevention and / or treatment of diseases, preferably, diseases related to NRF2 dysregulation such as tumors or cancer.

[0025] Another aspect of the present invention provides the compounds described herein, or stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or metabolites or prodrugs or pharmaceutically acceptable salts or esters thereof, or therapeutic combinations or pharmaceutical combinations described herein, or pharmaceutical compositions described herein, for the prevention and / or treatment of diseases, preferably, diseases related to NRF2 dysregulation such as tumors or cancer.

[0026] Another aspect of the present invention provides a method for preventing and / or treating a disease, the method comprising administering to an individual in need an effective amount of the compound of the present invention, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite or prodrug or pharmaceutically acceptable salt or ester thereof, or a therapeutic combination or pharmaceutical combination of the present invention, or a pharmaceutical composition of the present invention.

[0027] The diseases described in this invention are NRF2 dysregulation-related diseases such as tumors or cancer.

[0028] Another aspect of the present invention provides a method for preparing compound (I).

[0029] Terminology Definition

[0030] Unless otherwise defined below, all technical and scientific terms used herein are intended to have the same meaning as commonly understood by one of ordinary skill in the art. References to technical terms herein refer to techniques commonly understood in the art, including variations or equivalent substitutions of techniques that are obvious to one of ordinary skill in the art. While it is believed that the following terms will be well understood by one of ordinary skill in the art, the following definitions are set forth to better explain the invention.

[0031] The terms “comprising,” “including,” “having,” “containing,” or “involving,” and their other forms herein, are inclusive or open-ended and do not exclude other unlisted elements or method steps.

[0032] The term "alkyl" refers to a saturated aliphatic hydrocarbon group, including straight-chain and branched groups with 1 to 20 carbon atoms, preferably alkyl groups containing 1 to 6 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, and various branched isomers thereof. Alkyl groups can be substituted or unsubstituted. When substituted, the substituents can be substituted at any usable connection point, preferably one or more of the following groups, independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, oxo (=O), thio (=S), etc.

[0033] The term "hydroxyalkyl" refers to the aforementioned alkyl group that has been substituted with a hydroxyl group, such as C10. 1-6 Hydroxyalkyl refers to -C 1-6 Alkyl-OH.

[0034] The term "heteroalkyl" refers to an alkyl group in which one or more carbon atoms (and the hydrogen atoms attached thereto) are each independently replaced by the same or different heteroatom groups. Unless otherwise indicated, the heteroalkyl group comprises one, two, or three heteroatom groups, non-limiting examples of which include O, S, N, or NH, and typically has 1 to 12, 1 to 8, 1 to 6, 1 to 4, 1 to 3, or 1 to 2 carbon atoms. For example, the term "C 1-6 "Heteroalkyl" refers to a heteroalkyl group containing 1 to 6 carbon atoms and 1 to 3 heteroatom groups. The heteroatom groups can be placed at any position on the heteroalkyl group (e.g., internal or terminal), including positions where the heteroalkyl group is attached to the rest of the molecule. Typically, in the presence of more than one heteroatom group, the heteroatom groups are not adjacent to each other. Exemplary heteroalkyl groups include, but are not limited to, alkoxy, alkoxyalkylene, alkylamino, alkylaminoalkylene, dialkylamino, dialkylaminoalkylene, etc. The heteroalkyl group may optionally be substituted with one or more substituents selected from: oxo, hydroxy, amino, nitro, halogen, cyano, alkenyl, alkoxy, haloalkoxy, alkylamino, dialkylamino, haloalkylamino, halodialkylamino, cycloalkyl, cycloalkyloxy, heterocyclic, heterocyclic alkyl, heterocyclic alkyloxy, heteroaryl, heteroaryloxy, aryl, or aryloxy.

[0035] The term "cycloalkyl" or "carbocyclic" refers to a saturated cyclic hydrocarbon group, including but not limited to monocyclic and bicyclic alkyl groups (such as spirocyclic, fused-cyclic, and bridged-cyclic alkyl groups). The term "C"... 3-10 "Cycloalkyl" refers to a cycloalkyl group having 3 to 10 (e.g., 3-8, 3-6, 3-4) cyclic carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc. The cycloalkyl group can be substituted or unsubstituted, wherein the cycloalkyl group can be independently unsubstituted or substituted by one or more substituents described in this invention, such as H, deuterated, oxo, thio, halogen, OH, CN, C as described in this invention. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR 5 R 6 The substituents are replaced by the substituents.

[0036] The term "heterocyclic group" or "heterocycle" refers to a 3- to 12-membered non-aromatic cyclic group consisting of 2 to 11 carbon atoms and 1 to 6 heteroatoms selected from nitrogen, oxygen, and sulfur. Examples include 3-12-membered heterocyclic groups, 3-8-membered heterocyclic groups, 3-6-membered heterocyclic groups, and 4-6-membered heterocyclic groups. Heterocyclic groups can be saturated or partially unsaturated. Unless otherwise specifically indicated in this specification, heterocyclic groups can be monocyclic, bicyclic, tricyclic, or more ring systems, which may include fused ring systems, fused ring systems, bridged ring systems, or spirocyclic systems. For the purposes of this application, the heterocyclic group is preferably a 3- to 12-membered non-aromatic monocyclic or bicyclic group containing one to two heteroatoms selected from nitrogen, oxygen, and sulfur, such as a 3- to 8-membered non-aromatic monocyclic group containing one to two heteroatoms selected from nitrogen, oxygen, and sulfur, or a 3- to 6-membered non-aromatic monocyclic group containing one to two heteroatoms selected from nitrogen and oxygen; or a 3- to 12-membered non-aromatic bicyclic group; or a 3- to 12-membered non-aromatic cyclic bicyclic group with an aromatic ring. The bicyclic group includes fused bicyclic, fused bicyclic, bridged bicyclic, or spirocyclic groups, such as a 3- to 12-membered heterocyclic group with a 5- to 6-membered heteroaryl group. The nitrogen, carbon, or sulfur atom in the heterocyclic group may optionally be oxidized; the nitrogen atom may optionally be quaternized; and the heterocyclic group may be partially unsaturated or fully saturated. The heterocyclic group may be connected to the rest of the molecule via a carbon atom or heteroatom and through a single bond. Examples of heterocyclic groups include, but are not limited to: azirrobutyl, pyranyl, tetrahydropyranyl, thiaranyl, tetrahydrofuranyl, morpholinyl, thiomorpholinyl, pyrazolyl, dihydropyrazolyl, piperazinyl, piperidinyl, pyrrolidinyl, oxazinyl, dioxocyclopentyl, tetrahydroisoquinolinyl, decahydroisoquinolinyl, imidazolinyl, imidazoalkyl, quinazinyl, thiazoalkyl, isothiazolyl, isoxazolyl, dihydroindolyl, octahydroindolyl, octahydroisoindolyl, pyrazolyl, phthalimide, azirrobicyclo[3.1.0]hexyl, azirrocyclo[2.4]heptyl, and groups of the following formula: wait.

[0037] The term "halogenated" or "halogenated" is defined as including F, Cl, Br, or I.

[0038] The term "halogenated alkyl" refers to the aforementioned alkyl group that has been substituted with a halogen. For example, "C 1-6"Haloalkyl" refers to a C-aryl group substituted with one or more (e.g., 1, 2, 3, or 4) halogens. 1-6 alkyl.

[0039] The term "alkoxy" refers to an alkyl group, as defined above, that is attached to a parent molecule via an oxygen atom. C 1-6 Representative examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, n-butoxy, isobutoxy, tert-butoxy, pentoxy, and hexoxy.

[0040] The term "haloalkoxy" refers to the alkoxy group described above, such as C10. 1-6 A group obtained by substituting one or more (e.g., 1, 2, 3, or 4) hydrogen atoms of an alkoxy group with a halogen (e.g., fluorine, chlorine, bromine, or iodine), such as C. 1-2 Halogenated alkoxy, halogenated methoxy, halogenated ethoxy, C3-halogenated alkoxy, C4-halogenated alkoxy, C 1-2 Fluoroalkoxy, fluoromethoxy, fluoroethoxy, C3 fluoroalkoxy, C4 fluoroalkoxy, C 1-2 Chloroalkoxy, chloromethoxy, chloroethoxy, C3 chloroalkoxy, C4 chloroalkoxy. Specific examples include, but are not limited to, fluoromethoxy, difluoromethoxy, trifluoromethoxy, trifluoroethoxy, chloroethoxy, etc.

[0041] The term "alkenyl" refers to an aliphatic hydrocarbon group containing at least one carbon-carbon double bond and in which one hydrogen atom is replaced by a bond. The alkenyl group can be straight-chain or branched and contains from about 2 to about 15 carbon atoms. In one embodiment, the alkenyl group contains from about 2 to about 12 carbon atoms. In another embodiment, the alkenyl group contains from about 2 to about 6 carbon atoms. The term "C 2-6 "Alkenyl" refers to an alkenyl group with 2 to 6 carbon atoms. Non-limiting examples of alkenyl groups include vinyl, propenyl, n-butenyl, 3-methylbut-2-enyl, and n-pentenyl. The alkenyl group can be unsubstituted or substituted with one or more of the same or different substituents, each substituent being independently selected from halogens, alkenyl, alkynyl, aryl, cycloalkyl, cyano, hydroxyl, -O-alkyl, -O-aryl, -alkylene-O-alkyl, alkylthio, -NH2, -NH(alkyl), -N(alkyl)2, -NH(cycloalkyl), -OC(O)-alkyl, -OC(O)-aryl, -OC(O)-cycloalkyl, -C(O)OH, and -C(O)O-alkyl.

[0042] Term "C" 2-6 "Alkyne" refers to a linear or branched monovalent hydrocarbon group that contains one or more triple bonds and has 2, 3, 4, 5, or 6 carbon atoms, particularly 2 or 3 carbon atoms ("C"). 2-3 The C group ("alkynyl group"). 2-6Alkynyl groups include, for example, ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl, but-3-ynyl, pent-1-ynyl, pent-2-ynyl, pent-3-ynyl, pent-4-ynyl, hex-1-ynyl, hex-2-ynyl, hex-3-ynyl, hex-4-ynyl, hex-5-ynyl, 1-methylprop-2-ynyl, 2-methylbut-3-ynyl, 1-methylbut-3-ynyl, 1-methylbut-2-ynyl, 3-methylbut-1-ynyl, 1-ethylprop-2-ynyl, 3-methylpent-4-ynyl, 2-methylpent-4-ynyl The alkynyl group includes 1-methylpentan-4-alkynyl, 2-methylpentan-3-alkynyl, 1-methylpentan-3-alkynyl, 4-methylpentan-2-alkynyl, 1-methylpentan-2-alkynyl, 4-methylpentan-1-alkynyl, 3-methylpentan-1-alkynyl, 2-ethylbutan-3-alkynyl, 1-ethylbutan-3-alkynyl, 1-ethylbutan-2-alkynyl, 1-propylpropan-2-alkynyl, 1-isopropylpropan-2-alkynyl, 2,2-dimethylbutan-3-alkynyl, 1,1-dimethylbutan-3-alkynyl, 1,1-dimethylbutan-2-alkynyl, or 3,3-dimethylbutan-1-alkynyl. In particular, the alkynyl group is ethynyl, propan-1-alkynyl, or propan-2-alkynyl.

[0043] The term "aryl" or "aromatic ring" refers to a C group with a conjugated π-electron system. 6-14 All-carbon monocyclic or fused polycyclic (i.e., rings sharing adjacent carbon atom pairs) groups, preferably C 6-10 Aryl groups, such as phenyl and naphthyl, more preferably phenyl. The aryl ring may be fused to a heteroaryl, heterocyclic, or cycloalkyl ring, wherein the ring attached to the parent structure is an aryl ring.

[0044] The aryl group can be substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups, independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxyl or carboxylic acid ester group.

[0045] The terms "5-10 membered heteroaryl" or "5-10 membered heteroaryl ring" refer to an aromatic monocyclic or polycyclic system containing about 5 to about 10 ring atoms, wherein 1 to 4 ring atoms are independently O, N, or S, and the remaining ring atoms are carbon atoms. In another embodiment, the heteroaryl or heteroaryl ring is a monocyclic heteroaryl and has 5 or 6 ring atoms. In another embodiment, the heteroaryl or heteroaryl ring is a bicyclic heteroaryl. The heteroaryl group may optionally be substituted with one or more "cyclic substituents," which may be the same or different, and the heteroaryl group is as defined herein. The heteroaryl group is linked by a ring carbon atom, and any nitrogen atom of the heteroaryl group may optionally be oxidized to the corresponding N-oxide. Any C atom of the heteroaryl group may optionally be oxidized or thiolated. The term "heteroaryl" also includes heteroaryl groups defined above fused with cycloalkyl groups. Non-limiting examples of heteroaryl groups include: pyridyl, pyrazinyl, furanyl, thiopheneyl, pyrimidinyl, pyridone (including N-substituted pyridones), isoxazolyl, isothiazolyl, oxazolyl, oxadiazolyl, thiazolyl, pyrazolyl, furazolyl, pyrroleyl, triazolyl, 1,2,4-thiadiazolyl, pyrazinyl, pyridazinyl, quinoxalinyl, phthalazinyl, oxindolyl, imidazo[1] [2-a]pyridyl, imidazo[2,1-b]thiazolyl, benzofurazanyl, indolyl, azaindolyl, benzimidazolyl, benzothiophene, quinolinyl, imidazolyl, benzimidazolyl, thiophene-pyridyl, quinazolinyl, thiophene-pyrimidinyl, pyrrolopyridyl, imidazopyridyl, isoquinolinyl, benzoazaindolyl, 1,2,4-triazinyl, benzothiazolyl, etc., and all their isomers. In one embodiment, the heteroaryl group is a 5-membered heteroaryl group. In another embodiment, the heteroaryl group is a 6-membered heteroaryl group, such as a 6-membered nitrogen-containing heteroaryl group.

[0046] The term "substitution" refers to the selective replacement of one or more (e.g., one, two, three, or four) hydrogen atoms on a specified atom by a specified group, provided that the substitution does not exceed the normal valence of the specified atom in the present case and the substitution forms a substantially stable compound. Combinations of substituents and / or variables are permitted only if such combinations form a substantially stable compound.

[0047] The term “optionally” means that the groups or substituents described herein may be unsubstituted or substituted by specific groups or radicals.

[0048] The term "one or more" means one or more under reasonable conditions, such as two, three, four, five or ten.

[0049] When the bond of a substituent is such that it passes through the ring and connects two atoms, then such a substituent can be bonded to any cyclic atom in the substituted ring.

[0050] The text appears This indicates that the ring contains 0, 1, 2, or more double bonds, for example... This indicates whether the ring is saturated or unsaturated. (This is a recurring term in the text.) This indicates that the ring is a conjugated system and has aromatic properties.

[0051] The text uses Indicates the connection point on the ring, for example This can indicate that the loop forms a parallel loop with other loops through the connection points shown, and the bond where the wavy line is located can be a single bond or a double bond.

[0052] If a compound, group or substituent described herein is described as being "optionally" substituted with a specified group or radical, it means that the compound, group or substituent may be (1) unsubstituted or (2) substituted with the specified group or radical.

[0053] If a substituent or number is described as "each independently selected from" a set of groups or numbers, then each substituent or number is selected independently of the others. Therefore, each substituent or number may be the same as or different from another (other) substituent or number.

[0054] If a substituent is described as “each independently and optionally selected from” a group of groups, then each substituent is selected independently of the others. Thus, each substituent may be the same as or different from another (other) substituent, and the compounds, groups, or substituents described herein may be unsubstituted or substituted with the specified groups or radicals.

[0055] This invention also includes all pharmaceutically acceptable isotopically labeled compounds that are identical to the compounds of this invention, except that one or more atoms are replaced by atoms having the same atomic number but with an atomic mass or mass number different from the dominant atomic mass or mass number in nature. Examples of isotopes suitable for inclusion in the compounds of this invention include, but are not limited to, isotopes of hydrogen (e.g., 2 H, 3 H, deuterium (D), tritium (T); carbon isotopes (e.g., H, deuterium (D), tritium (T)); 11 C 13 C and 14 C); isotopes of chlorine (e.g.) 37 Cl); isotopes of fluorine (e.g., Cl); 18 F); isotopes of iodine (e.g., F); 123 I and 125 I); nitrogen isotopes (e.g.) 13 N and 15 N); isotopes of oxygen (e.g., N); 15 O、 17 O and 18 O); isotopes of phosphorus (e.g., O); phosphorus isotopes ... 32P); and isotopes of sulfur (e.g. 35 S). Certain isotope-labeled compounds of the present invention (e.g., those doped with radioactive isotopes) can be used in drug and / or substrate tissue distribution studies (e.g., analysis). Radioactive isotope tritium (i.e. 3 H) and carbon-14 (i.e. 14 C) It is particularly suitable for this purpose due to its ease of incorporation and detection. Using positron-emitting isotopes (e.g.) 11 C 18 F, 15 O and 13 Substitution of N) can be used in positron emission tomography (PET) studies to examine substrate acceptor occupancy. The isotopically labeled compounds of the present invention can be prepared by methods similar to those described in the accompanying routes and / or examples and preparations, by using a suitable isotopically labeled reagent instead of the previously used unlabeled reagent. Pharmaceutically acceptable solvates of the present invention include those in which the crystallization solvent can be isotopically substituted, for example, D2O, acetone-d6, or DMSO-d6.

[0056] As used herein, the term "suitable substituent" refers to modifications of a compound that can be made by those skilled in the art to suit the needs of the compound's substituents. "Suitable substituents" include, but are not limited to, oxo (=O), thio (=S), halogens, cyano groups, and NR groups. 5 R 6 Carboxyl, mercapto, hydroxyl, nitro, ester (e.g., -C) 1-6 Alkyl-C(=O)-OC 1-6 Alkyl), C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkyl-OC 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, 3-10 membered heterocyclic, 5-10 membered heteroaryl, C 6-10 Aryl, benzyl, hydroxy-substituted benzyl, indolylmethylene, C 1-6 Haloalkoxy, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)-NR a R b -C(=O)-C 1-6 Alkyl group, -OC(=O)-C1-6 Alkyl groups and -C(=O)-OC 1-6 alkyl.

[0057] Whether explicitly stated or not, all numerical values ​​in this application are modified by the term “about”. The term “about” means within ±20%, ±10%, ±5%, or ±2% of the stated numerical value.

[0058] The term "stereoisomer" refers to isomers formed due to the presence of at least one asymmetric center in a compound. In compounds having one or more (e.g., one, two, three, or four) asymmetric centers, racemic mixtures, single enantiomers, mixtures of diastereomers, and individual diastereomers can be produced. Specific individual molecules may also exist as geometric isomers (cis / trans). Similarly, the compounds of the present invention can exist as mixtures of two or more structurally different forms in rapid equilibrium (commonly referred to as tautomers). Representative examples of tautomers include keto-enol tautomers, phenol-keto tautomers, nitroso-oxime tautomers, imine-enamine tautomers, etc. It is to be understood that the scope of this application covers all such isomers or mixtures thereof in any proportion (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%).

[0059] This invention covers all possible crystalline forms or polymorphs of the compounds of this invention, which may be a single polymorph or a mixture of more than one polymorph in any proportion.

[0060] It should also be understood that certain compounds of the present invention may exist in a free form for therapeutic purposes, or, where appropriate, in their pharmaceutically acceptable derivative forms. According to the present invention, pharmaceutically acceptable derivatives include, but are not limited to, pharmaceutically acceptable salts, esters, solvates, metabolites, isotope-labeled substances, or prodrugs, which, upon administration to a patient in need, can directly or indirectly provide the compounds of the present invention or their metabolites or residues. Therefore, when referring to "compounds of the present invention" herein, it is also intended to cover the various derivative forms of the compounds described above.

[0061] Pharmaceutically acceptable salts of the compounds of the present invention include their acid addition salts and base addition salts. Suitable acid addition salts are formed by acids that form pharmaceutically acceptable salts. Suitable base addition salts are formed by bases that form pharmaceutically acceptable salts. A review of suitable salts can be found in Stahl and Wermuth's "Handbook of Pharmaceutical Salts: Properties, Selection, and Use" (Wiley-VCH, 2002). Methods for preparing pharmaceutically acceptable salts of the compounds of the present invention are known to those skilled in the art.

[0062] The term "ester" refers to esters derived from the various general formula compounds of this application, including physiologically hydrolyzable esters that can be hydrolyzed under physiological conditions to release the compounds of the present invention in the form of free acids or alcohols. The compounds of the present invention may themselves also be esters.

[0063] The compounds of the present invention can exist as solvates (preferably hydrates), wherein the compounds of the present invention contain a polar solvent as a structural element of the lattice of the compound. The amount of the polar solvent, particularly water, can be stoichiometric or non-stoichiometric.

[0064] Those skilled in the art will understand that not all nitrogen-containing heterocycles can form N-oxides because nitrogen requires available lone pairs of electrons to be oxidized into oxides; those skilled in the art will identify nitrogen-containing heterocycles that can form N-oxides. Those skilled in the art will also recognize that tertiary amines can form N-oxides. Synthetic methods for preparing N-oxides of heterocycles and tertiary amines are well known to those skilled in the art, including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic acid and m-chloroperoxybenzoic acid (MCPBA), hydrogen peroxide, alkyl peroxides such as tert-butyl peroxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for preparing N-oxides have been extensively described and reviewed in the literature, see, for example: T.L. Gilchrist, Comprehensive Organic Synthesis, vol. 7, pp. 748-750; A.R. Katritzky and A.J. Boulton, Eds., Academic Press; and G.W. H. Heeseman and E.S. G. Wierstiuk, Advances in Heterocyclic Chemistry, vol. 22, pp. 390-392, A.R. Katritzky and A.J. Boulton, Eds., Academic Press.

[0065] The scope of this invention also includes metabolites of the compounds of this invention, i.e., substances formed in the body when the compounds of this invention are administered. Such products can be generated, for example, by oxidation, reduction, hydrolysis, amidation, deamidation, esterification, enzymatic hydrolysis, etc., of the administered compound. Therefore, this invention includes metabolites of the compounds of this invention, including compounds obtained by methods that expose the compounds of this invention to mammals for a time sufficient to produce their metabolites.

[0066] This invention further includes, within its scope, prodrugs of the compounds of the invention, which are certain derivatives of the compounds of the invention that may themselves have little or no pharmacological activity, and which, when administered to or onto the body, can be converted, for example, by hydrolysis and cleavage into the compounds of the invention having the desired activity. Typically, such prodrugs are functional group derivatives of the compounds that are readily converted in vivo into the compounds with the desired therapeutic activity. Further information regarding the use of prodrugs can be found in “Pro-drugs as Novel Delivery Systems,” Vol. 14, ACS Symposium Series (T. Higuchi and V. Stella) and “Bioreversible Carriers in Drug Design,” Pergamon Press, 1987 (EB Roche, editor, American Pharmaceutical Association). The prodrugs of the invention can be prepared, for example, by replacing suitable functional groups present in the compounds of the invention with certain portions known to those skilled in the art as “pro-moiety” (e.g., as described in “Design of Prodrugs,” H. Bundgaard (Elsevier, 1985)).

[0067] In any process of preparing the compounds of the present invention, protection of sensitive or reactive groups on any relevant molecule may be necessary and / or desired, thereby forming a form of chemical protection for the compounds of the present invention. This can be achieved by conventional protecting groups, for example, those described in Protective Groups in Organic Chemistry, ed. J.F.W. McOmie, Plenum Press, 1973; and T.W. Greene & P. ​​G.W. Uts, Protective Groups in Organic Synthesis, John Wiley & Sons, 1991, which are incorporated herein by reference. Protecting groups can be removed at appropriate subsequent stages using methods known in the art.

[0068] compound

[0069] In one embodiment, the present invention provides a compound, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite, prodrug, or pharmaceutically acceptable salt or ester thereof, wherein said compound has a structure as shown in formula (I):

[0070] Among them, ring A is selected from 3-12 membered carbon rings, 3-12 membered heterocycles, and C. 6-10 Aromatic rings and 5-10 heterocyclic aromatic rings;

[0071] X 2 Selected from N and CR 3 ;

[0072] X 1 Selected from O, S (=O)2, -C (=C) 1-6 alkyl)-, -C(=C 1-6 (halogenated alkyl)-, CR 5 R 6 and NR 7 ;

[0073] R 1 Selected from C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, the C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Each alkynyl group is independently and optionally replaced by one or more substituents selected from H, deuterium, CN and halogens;

[0074] R 2 Each is independently selected from H, halogen, OH, C 1-6 Alkyl, C 2-6 alkenyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl groups and -C(=O)-(CH2) p -NR a R b The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl groups and -C(=O)-(CH2) p -NR aR b Each is independently and optionally influenced by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6- 10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR 5 R 6 Substituents are replaced by; and / or,

[0075] Two Rs 2 The atoms or R connected to it 2 R 7 The atoms connected to it together form C 3-10 Cycloalkyl, 3-12-membered heterocyclic or 5-10-membered heteroaryl, wherein the C 3-10 The cycloalkyl, 3-12-membered heterocyclic and 5-10-membered heteroaryl groups are each independently and optionally separated by one or more elements selected from halogen, H, OH, CN, -NR. 5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OC 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Substituents of aryl and 5-10 heteroaryl groups;

[0076] R 3 Each is independently selected from H, halogens, CN, OH, NO2, -NR 5 R6 C 1-6 Alkyl, C 1-6 Alkoxy, carboxyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, oxo groups, thio groups, C 3-10 cycloalkyl, -OC 3-10 Cycloalkyl and 3-12 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, carboxyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, oxo groups, thio groups, C 3-10 cycloalkyl, -OC 3-10 The cycloalkyl group and the 3-12 membered heterocyclic group are each independently and optionally surrounded by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl groups, -C(=O)-OH, NO2, and -NR 5 R 6 The substituents are replaced;

[0077] R 4 Selected from H, deuterium, halogen, oxo group, thio group, CN, OR 7 SR 7 S(=O)R 7 S(=O)2R 7 NO2, -NR 5 R 6 -NR 7 S(=O)2R c -S(=O)2N R 5 R 6-C(=O)R 7 -C(=O)OR 7 -C(=O)NR 5 R 6 -OC(=O)NR 5 R 6 -NR 7 C(=O)2R c -NR 7 C(=O)2NR 5 R 6 -NR 7 C(=O)2OR c C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl and 3-12 membered heterocyclic, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3-10 cycloalkyl, C 6-10 The aryl, 5-10 membered heteroaryl, and 3-12 membered heterocyclic groups are each independently and optionally bound by one or more groups selected from H, halogen, OH, CN, -COOH, oxo, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, C 1-6 Haloalkyl, C 1- 6-Haloalkoxy, -OC 3-10 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0078] Two Rs 4 The atoms connected to it together form C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more elements selected from H, halogen, OH, CN, -NR. 5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OC 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Substituents of aryl and 5-10 heteroaryl groups;

[0079] R 5 R 6 and R 7 Each is independently selected from H, halogen, OH, CN, C 1-6 Alkyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-12 membered heterocyclic group, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-12 membered heterocyclic group, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR a R b -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR a R b The substituents are replaced;

[0080] Or, R 5 and R 6 The atoms connected to it together form C 3-10 Cycloalkyl or 3-12 membered heterocyclic groups, wherein the C 3- 10 The cycloalkyl group and the 3-12 membered heterocyclic group are each independently and optionally surrounded by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR a R b -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR a R b The substituents are replaced;

[0081] R a and R bEach is independently selected from H and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Heteroalkyl, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Heteroalkyl, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more elements selected from H, halogen, OH, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-10 Substituents of cycloalkyl groups;

[0082] R c Selected from H, OH, halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 1-6 Haloalkyl, C 1- 6-alkoxy, C 1-6 Halogenated alkoxy groups, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2- 6-alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1- 6-alkyl, -S(=O)2-C 6-10 Aryl, -C(=O)NR5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR 5 R 6 The substituents are replaced;

[0083] p is selected from 0, 1, 2, 3, 4, 5, and 6;

[0084] m and n are each independently selected from 0, 1, 2, 3 and 4.

[0085] In some implementations, R 2 Each is independently selected from H, halogen, OH, C 1-6 Alkyl, C 2-6 alkenyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl groups and -C(=O)-(CH2) p -NR a R b The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl groups and -C(=O)-(CH2) p -NR a R b Each is independently and optionally influenced by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR 5 R 6 The substituents are replaced;

[0086] Or, two Rs 2 The atoms or R connected to it 2 R 7 The atoms connected to it together form C 3-10 Cycloalkyl, 3-12-membered heterocyclic or 5-10-membered heteroaryl, wherein the C 3-10 The cycloalkyl, 3-12-membered heterocyclic and 5-10-membered heteroaryl groups are each independently and optionally separated by one or more elements selected from halogen, H, OH, CN, -NR. 5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OC 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Substituents of aryl and 5-10 heteroaryl groups;

[0087] R 4 Selected from H, deuterium, halogen, oxo group, thio group, CN, OR 7 SR 7 S(=O)R 7 S(=O)2R 7 NO2, -NR 5 R 6 -NR 7 S(=O)2R c -S(=O)2N R 5 R 6 -C(=O)R 7 -C(=O)OR 7 -C(=O)NR 5 R 6 -OC(=O)NR 5 R 6 -NR 7 C(=O)2R c -NR 7 C(=O)2NR 5 R 6-NR 7 C(=O)2OR c C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl and 3-12 membered heterocyclic, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3-10 cycloalkyl, C 6-10 The aryl, 5-10-membered heteroaryl, and 3-12-membered heterocyclic groups are each independently and optionally bound by one or more elements selected from H, halogen, OH, CN, -COOH, C. 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-10 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0088] Or, two Rs 4 The atoms connected to it together form C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more elements selected from H, halogen, OH, CN, -NR. 5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OC 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Substituents of aryl and 5-10 heteroaryl groups.

[0089] In some embodiments, ring A is selected from 3-12 membered heterocyclic rings and 5-10 membered heteroaromatic rings.

[0090] In some embodiments, ring A is selected from 3-10-membered heterocycles, 3-8-membered heterocycles, 3-6-membered heterocycles, or 5-6-membered heteroaromatic rings.

[0091] In some embodiments, ring A is selected from 3-12-membered heterocycles and 5-10-membered heteroaromatic rings, wherein the 3-12-membered heterocycles and 5-10-membered heteroaromatic rings contain one, two or three heteroatoms selected from N, O and / or S.

[0092] In some embodiments, ring A is selected from 3-10-membered heterocycles and 5-10-membered heteroaromatic rings, wherein the 3-10-membered heterocycles and 5-10-membered heteroaromatic rings contain one, two or three heteroatoms selected from N, O and / or S.

[0093] In some embodiments, ring A is selected from 3-8 membered heterocycles and 5-10 membered heteroaromatic rings, wherein the 3-8 membered heterocycles and 5-10 membered heteroaromatic rings contain one, two or three heteroatoms selected from N, O and / or S.

[0094] In some embodiments, ring A is selected from 3-6 membered heterocycles and 5-6 membered heteroaromatic rings, wherein the 3-8 membered heterocycles and 5-6 membered heteroaromatic rings contain one, two or three heteroatoms selected from N, O and / or S.

[0095] In some embodiments, ring A is selected from 3-6 membered heterocycles and 5-6 membered heteroaromatic rings, wherein the 3-6 membered heterocycles and 5-6 membered heteroaromatic rings contain one, two or three heteroatoms selected from N, O and / or S.

[0096] In some embodiments, ring A is selected from a 6-membered heterocycle containing one or two heteroatoms selected from N and O.

[0097] In some embodiments, ring A is selected from 5-6 membered heteroaromatic rings, which contain one, two or three heteroatoms selected from N, O and / or S.

[0098] In some implementations, heteroatoms in ring A are positioned adjacent, alternating, or opposite to each other.

[0099] In some embodiments, ring A contains two heteroatoms, and the two heteroatoms are in adjacent, alternating, or opposite positions.

[0100] In some embodiments, the compound has a structure as shown in formula (I-1'):

[0101] Where q is selected from 0, 1, 2, and 3; X3 X 4 X 5 and X 6 Each is independently selected from N and NR. 7 O, S, S(=O)2, CR 5 R 6 and CR 4 ;

[0102] X 1 X 2 R 1 R 2 R 3 R 4 R 5 R 6 R 7 m and n are as defined above.

[0103] In some implementations, X 2 Selected from N and CH.

[0104] In some implementations, X 2 Selected from CR 3 Preferably, X 2 For CH.

[0105] In some embodiments, the compound has a structure as shown in formula (I-1):

[0106] Where q is selected from 0, 1, 2, and 3; X 3 X 4 X 5 and X 6 Each is independently selected from N and NR. 7 O, S, S(=O)2, CR 5 R 6 and CR 4 ;

[0107] X 1 R 1 R 2 R 3 R 4 R 5 R 6 R 7 m and n are as defined above.

[0108] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from 5-10-membered heteroaryl and 3-12-membered heterocyclic groups, such as 3-10-membered heterocyclic groups, 3-8-membered heterocyclic groups and 6-membered heterocyclic groups.

[0109] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from 5-10 heteroaryl and 3-10 heterocyclic groups.

[0110] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from 5-10 membered heteroaryl and 3-8 membered heterocyclic groups.

[0111] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from 5-6 membered heteroaryl and 3-6 membered heterocyclic groups.

[0112] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from 5-6 member heteroaryl groups containing N, O and / or S atoms and 3-6 member heterocyclic groups containing N, O and / or S atoms.

[0113] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from 5-6 member heteroaryl groups containing N and / or O atoms and 3-6 member heterocyclic groups containing N and / or O atoms.

[0114] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, oxazolyl, pyrazolyl, morpholinyl, thiazolyl, isothiazolyl, pyrroleyl, isoxazolyl, furanyl, thiophenyl, imidazoleyl, triazolyl.

[0115] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl, morpholinyl, thiazolyl,

[0116] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl, morpholinyl, thiazolyl,

[0117] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl, morpholinyl, thiazolyl,

[0118] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from 5-10-membered heteroaryl and 3-12-membered heterocyclic groups, such as 3-10-membered heterocyclic groups, 3-8-membered heterocyclic groups and 6-membered heterocyclic groups.

[0119] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from 5-10 heteroaryl and 3-10 heterocyclic groups.

[0120] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from 5-10 membered heteroaryl and 3-8 membered heterocyclic groups.

[0121] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from 5-6 membered heteroaryl and 3-6 membered heterocyclic groups.

[0122] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from 5-6 member heteroaryl groups containing N, O and / or S atoms and 3-6 member heterocyclic groups containing N, O and / or S atoms.

[0123] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from 5-6 member heteroaryl groups containing N and / or O atoms and 3-6 member heterocyclic groups containing N and / or O atoms.

[0124] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, oxazolyl, pyrazolyl, morpholinyl, thiazolyl, isothiazolyl, pyrroleyl, isoxazolyl, furanyl, thiophenyl, imidazoleyl, triazolyl.

[0125] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl, morpholinyl, thiazolyl,

[0126] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl, morpholinyl, thiazolyl,

[0127] In some embodiments, the compounds of formula (I-1) and formula (I-1') provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl, morpholinyl, thiazolyl,

[0128] In some implementations, X 3 X 4 X 5 and X 6 Each is independently selected from N, O, CH, S, NH and CH2.

[0129] In some implementations, X 3 X 4 X 5 and X 6 Each is independently selected from N, O, and CH.

[0130] In some embodiments, the compounds of formula (I-1) and formula (I-1') have any of the following characteristics:

[0131] (1)X 3 For O, X 4 For CH and CH2, X 5 Selected from N and NH, X 6 Selected from O, S, CH and CH2;

[0132] (2)X 3 Selected from N and NH, X 4 Selected from CH and CH2, X 5 Selected from N and NH, X 6 Selected from O, S, CH and CH2;

[0133] (3)X 3 Selected from CH and CH2, X 4 Selected from N and NH, X 5 Selected from N and NH, X 6 Selected from O, S, CH and CH2;

[0134] (4)X 3 Selected from N and NH, X 4 Selected from CH and CH2, X 5 Selected from CH and CH2, X 6 Selected from O, S, CH and CH2;

[0135] (5)X 3 Selected from N and NH, X 4 Selected from CH and CH2, X 5 For O, X 6 Selected from O, S, CH and CH2;

[0136] (6)X 3 Selected from CH and CH2, X 4 Selected from N and NH, X 5 Selected from CH and CH2, X 6 Selected from O, S, CH and CH2;

[0137] (7)X 3 For O, X 4 Selected from N and NH, X 5 Selected from CH and CH2, X 6 Selected from O, S, CH and CH2;

[0138] (8)X 3 For O, X 4 Selected from CH and CH2, X 5 Selected from CH and CH2, X 6 Selected from O, S, CH and CH2;

[0139] (9)X 3 Selected from N and NH, X 4 Selected from CH and CH2, X 5 Let S and X be the values ​​of S and X. 6 Selected from O, S, CH and CH2;

[0140] (10)X 3 Selected from CH and CH2, X 4 Selected from CH and N, X 5 Selected from NH, CH and CH2, X 6 Selected from O, S, CH and CH2;

[0141] (11)X 3 Selected from CH and CH2, X 4 Selected from CH and CH2, X 5 For N and NH, X 6 Selected from O, S, CH and CH2;

[0142] (12)X 3 Selected from S, X 4Selected from NH and N, X 5 For CH and CH2, X 6 Selected from O, S, CH and CH2;

[0143] (13)X 3 Selected from N and NH, X 4 Selected from NH and N, X 5 For NH and N, X 6 Selected from O, S, CH and CH2;

[0144] (14)X 3 Selected from S, X 4 Selected from CH and CH2, X 5 For NH and N, X 6 Selected from O, S, CH and CH2;

[0145] (15)X 3 Let S and X be the values ​​of S and X. 4 Selected from N and CH, X 5 Selected from CH and N, X 6 Selected from O, S, CH and CH2;

[0146] (16)X 3 Selected from S, X 4 Selected from CH and CH2, X 5 For CH and CH2, X 6 Selected from O, S, CH and CH2;

[0147] (17)X 3 Let N, X 4 Selected from N and CH, X 5 Selected from NH, X 6 Selected from O, S, CH and CH2.

[0148] In some implementations, q is selected from 0 and 1.

[0149] In some embodiments, the compound has a structure as shown in formula (I-1-A):

[0150] Where q is selected from 0, 1, 2, and 3; X 3 X 4 and X 5 Each is independently selected from N and NR. 7 O, S, S(=O)2, CR 5 R 6 and CR 4 ;

[0151] X 1 R 1 R 2 R3 R 4 R 5 R 6 R 7 m and n are as defined above.

[0152] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from 5-10-membered heteroaryl and 3-12-membered heterocyclic groups, such as 3-10-membered heterocyclic groups, 3-8-membered heterocyclic groups and 6-membered heterocyclic groups.

[0153] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from 5-10 heteroaryl and 3-10 heterocyclic groups.

[0154] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from 5-10 membered heteroaryl and 3-8 membered heterocyclic groups.

[0155] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from 5-6 membered heteroaryl and 3-6 membered heterocyclic groups.

[0156] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from 5-6 member heteroaryl groups containing N, O and / or S atoms and 3-6 member heterocyclic groups containing N, O and / or S atoms.

[0157] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from 5-6 member heteroaryl groups containing N and / or O atoms and 3-6 member heterocyclic groups containing N and / or O atoms.

[0158] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl, morpholinyl, thiazolyl,

[0159] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, oxazolyl, pyrazolyl, thiazolyl,

[0160] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl, morpholinyl, thiazolyl,

[0161] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl,

[0162] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl,

[0163] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl,

[0164] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl,

[0165] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from 5-10-membered heteroaryl and 3-12-membered heterocyclic groups, such as 3-10-membered heterocyclic groups, 3-8-membered heterocyclic groups and 6-membered heterocyclic groups.

[0166] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from 5-10 heteroaryl and 3-10 heterocyclic groups.

[0167] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from 5-10 membered heteroaryl and 3-8 membered heterocyclic groups.

[0168] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from 5-6 membered heteroaryl and 3-6 membered heterocyclic groups.

[0169] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from 5-6 member heteroaryl groups containing N, O and / or S atoms and 3-6 member heterocyclic groups containing N, O and / or S atoms.

[0170] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from 5-6 member heteroaryl groups containing N and / or O atoms and 3-6 member heterocyclic groups containing N and / or O atoms.

[0171] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, oxazolyl, pyrazolyl, morpholinyl, thiazolyl, isothiazolyl, pyrroleyl, isoxazolyl, furanyl, thiophenyl, imidazoleyl, triazolyl.

[0172] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl, morpholinyl, thiazolyl, isoxazolyl,

[0173] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl, morpholinyl, thiazolyl,

[0174] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, oxazolyl, pyrazolyl, thiazolyl,

[0175] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl, morpholinyl, thiazolyl,

[0176] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl,

[0177] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl,

[0178] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl,

[0179] In some embodiments, the compound of formula (I-1-A) provided by the present invention, wherein, Selected from pyridinyl, pyrazinyl, pyrazinyl, oxazolyl, pyrazolyl,

[0180] In some implementations, X 3 X 4 and X 5 Each is independently selected from N, O, CH, S, NH and CH2.

[0181] In some implementations, X 3 X 4 and X 5 Each is independently selected from N, O, and CH.

[0182] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention have any one of the following characteristics:

[0183] (1)X 3 For O, X 4 For CH, X 5 Let N be the number of people in the group.

[0184] (2)X 3 Let N, X 4 For CH, X 5 Let N be the number of people in the group.

[0185] (3)X 3 For CH, X 4 Let N, X 5 Let N be the number of people in the group.

[0186] (4)X 3 Let N, X 4 For CH, X 5 For CH;

[0187] (5)X 3 Let N, X 4 For CH, X 5 It is O;

[0188] (6)X 3 For CH, X4 Let N, X 5 For NH;

[0189] (7)X 3 CH2, X 4 For NH, X 5 It is CH2;

[0190] (8)X 3 For O, X 4 For NH, X 5 It is CH2;

[0191] (9)X 3 For O, X 4 CH2, X 5 It is CH2;

[0192] (10)X 3 For NH, X 4 CH2, X 5 It is O;

[0193] (11)X 3 For O, X 4 Let N, X 5 For CH;

[0194] (12)X 3 For O, X 4 For CH, X 5 For CH;

[0195] (13)X 3 For CH, X 4 For CH, X 5 For NH;

[0196] (14)X 3 Let S and X be the values ​​of S and X. 4 Let N, X 5 For CH;

[0197] (15)X 3 Let S and X be the values ​​of S and X. 4 For CH, X 5 For CH;

[0198] (16)X 3 Let S and X be the values ​​of S and X. 4 For CH, X 5 Let N be the number of people in the group.

[0199] (17)X 3 Let N, X 4 For CH, X 5 For NH;

[0200] (18)X 3 Let N, X4 Let N, X 5 For NH;

[0201] (19)X 3 Let N, X 4 For CH, X 5 For S; or,

[0202] (20)X 3 For CH, X 4 For NH, X 5 Let N be the number of elements in the array.

[0203] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention have any one of the following characteristics:

[0204] (1)X 3 For O, X 4 For CH, X 5 Let N be the number of people in the group.

[0205] (2)X 3 Let N, X 4 For CH, X 5 Let N be the number of people in the group.

[0206] (3)X 3 For CH, X 4 Let N, X 5 Let N be the number of people in the group.

[0207] (4)X 3 Let N, X 4 For CH, X 5 For CH;

[0208] (5)X 3 Let N, X 4 For CH, X 5 It is O;

[0209] (6)X 3 For CH, X 4 Let N, X 5 For NH;

[0210] (7)X 3 CH2, X 4 For NH, X 5 It is CH2;

[0211] (8)X 3 For O, X 4 For NH, X 5 It is CH2;

[0212] (9)X 3 For O, X 4CH2, X 5 It is CH2;

[0213] (10)X 3 For NH, X 4 CH2, X 5 It is O;

[0214] (11)X 3 Let N, X 4 For CH, X 5 For S; or,

[0215] (12)X 3 For CH, X 4 For NH, X 5 Let N be the number of elements in the array.

[0216] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) have any of the following characteristics:

[0217] (1)X 3 For O, X 4 For CH, X 5 Let N be the number of people in the group.

[0218] (2)X 3 Let N, X 4 For CH, X 5 Let N be the number of people in the group.

[0219] (3)X 3 For CH, X 4 Let N, X 5 Let N be the number of people in the group.

[0220] (4)X 3 Let N, X 4 For CH, X 5 For CH; or,

[0221] (5)X 3 Let N, X 4 For CH, X 5 It is O.

[0222] In some embodiments, the present invention provides compounds of formula (I-1), formula (I-1') and formula (I-1-A), wherein q is selected from 0 and 1.

[0223] In some embodiments, q is 0, and the compounds of formula (I-1), (I-1'), and (I-1-A) have any of the following characteristics:

[0224] (1)X 3 For O, X 4 For CH, X 5 Let N be the number of people in the group.

[0225] (2)X 3 For CH, X 4 Let N, X 5 Let N be the number of people in the group.

[0226] (3)X 3 For O, X 4 Let N, X 5 For CH;

[0227] (4)X 3 For O, X 4 For CH, X 5 For CH;

[0228] (5)X 3 For CH, X 4 For CH, X 5 For NH;

[0229] (6)X 3 Let S and X be the values ​​of S and X. 4 Let N, X 5 For CH;

[0230] (7)X 3 Let S and X be the values ​​of S and X. 4 For CH, X 5 For CH;

[0231] (8)X 3 Let N, X 4 For CH, X 5 For NH;

[0232] (9)X 3 Let N, X 4 Let N, X 5 For NH; or,

[0233] (10)X 3 Let S and X be the values ​​of S and X. 4 For CH, X 5 Let N be the number of elements in the array.

[0234] In some embodiments, q is 0, and the compounds of formula (I-1), (I-1'), and (I-1-A) have any of the following characteristics:

[0235] (1)X 3 For O, X 4 For CH, X 5 Let N be the number of people in the group.

[0236] (2)X 3 For CH, X 4 Let N, X 5 Let N be the number of elements in the array.

[0237] In some embodiments, q is 1, and the compounds of formula (I-1), (I-1'), and (I-1-A) have any of the following characteristics:

[0238] (1)X 3 Let N, X 4 For CH, X 5 Let N be the number of people in the group.

[0239] (2)X 3 For CH, X 4 Let N, X 5 Let N be the number of people in the group.

[0240] (3)X 3 Let N, X 4 For CH, X 5 For CH.

[0241] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 1 Selected from C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl groups (e.g., C) 2-4 (alkynyl group), the C 1-6 Alkyl, C 2-6 alkenyl and C 2- Each of the 6 alkynyl groups is independently and optionally replaced by one or more substituents selected from H, deuterium, CN, and halogens.

[0242] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 1 Selected from C 2-6 alkenyl and C 1-6 Haloalkyl, the C 2-6 alkenyl and C 1-6 Each haloalkyl group is optionally and independently replaced by one or more substituents selected from H, deuterium, CN and halogens.

[0243] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 1 Selected from C 2-6 alkenyl and C 1-4 Haloalkyl, the C 2-6 alkenyl and C 1-4 Each haloalkyl group is independently and optionally substituted by one or more substituents selected from H, deuterium, CN, F, Cl and Br.

[0244] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 1 Selected from vinyl, -CH2-CHCl2 and -CHCl2.

[0245] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 1 Selected from vinyl groups and -CH2-CHCl2. In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein X 1 Selected from O, -C (=C) 1-6 (halogenated alkyl)-, CR 5 R 6 and NR 7 In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein X 1 Selected from O, -C (=C) 1-6 Chloroalkyl)-, -C(=C 1-6 fluoroalkyl)-, CR 5 R 6 and NR 7 .

[0246] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein X 1 Selected from O, -C (=C) 1-6 fluoroalkyl)-, CR 5 R 6 and NR 7 .

[0247] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein X 1 Selected from O, -C (=CF2)-, -C (=CCl2)-, NR 7 And CF2.

[0248] In some embodiments, the compounds of formula (I), formula (I-1), and formula (I-1-A) provided by the present invention, wherein X 1 Selected from O, -C (=CF2)-, -C (=CCl2)- and NR 7 .

[0249] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein X1 Selected from O, -(C=CF2)-, NR 7 And CF2.

[0250] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein X 1 Selected from O, -(C=CF2)- and NR 7 .

[0251] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein X 1 Selected from O, -(C=CF2)- and NR 7 R 7 Each is independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy-C 1- 4-alkyl-, -C 1-4 Alkyl-CN, -C(=O)C 1-4 Alkyl groups, 3-6 membered heterocyclic groups (e.g., 3-6 membered heterocyclic groups containing N, O and / or S atoms), and 5-10 membered heteroaryl groups.

[0252] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein X 1 Selected from O, -(C=CF2)- and NR 7 R 7 Selected from 5-10 aryl compounds.

[0253] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein X 1 Selected from O, -(C=CF2)- and NR 7 R 7 Selected from 5-6 aryl heteroaryl groups.

[0254] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein X 1 Selected from O, -(C=CF2)- and NR 7 R 7 It is pyridyl.

[0255] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein X 1 It is O.

[0256] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein X 1 -C (=C) 1-6 (halogenated alkyl)-. In some embodiments, -C (=C 1-6 (Halogenated alkyl) is -C (=C) 1-6 Fluoroalkyl)-. In some embodiments, -C (=C 1-6 The haloalkyl group is -(C=CF2)-.

[0257] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein X 1 For CR 5 R 6 In some implementations, R 5 R 6 Each is independently selected from halogens. In some implementations, R 5 R 6 All are F.

[0258] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein X 1 For NR 7 In some implementations, R 7 Selected from C 1-4 Haloalkyl, C 1-4 Alkoxy-C 1-4 Alkyl-, -C 1-4 Alkyl-CN, -C(=O)C 1-4 Alkyl groups, 3-6 membered heterocyclic groups (e.g., 3-6 membered heterocyclic groups containing N, O, and / or S atoms), and 5-10 membered heteroaryl groups. In some embodiments, R 7 Selected from trifluoroethyl, -CH2CH2-OCH3, -CH2-CN, CH3(C=O)-, oxetane, and pyridinyl.

[0259] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 2 Each is independently selected from H, halogen, OH, C 1-6 Alkyl, C 2-6 alkenyl, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl groups and -C(=O)-(CH2)p -NR a R b The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl groups and -C(=O)-(CH2) p -NR a R b Each is independently and optionally influenced by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR 5 R 6 The substituents are replaced;

[0260] Or, R 2 R 7 The atoms bonded to it together form a 5-10 membered heteroaryl group, wherein the 5-10 membered heteroaryl group is optionally bonded by one or more atoms selected from C 1-6 Alkyl groups are substituted.

[0261] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 2 Each is independently selected from H, halogen, OH, C 1-6 Alkyl, C 2-6 alkenyl, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C1-6 Alkoxy, C 1-6 Halogenated alkoxy groups and C 1-6 hydroxyalkyl, the C 1-6 Alkyl, C 2-6 alkenyl, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups and C 1-6 Each hydroxyalkyl group is optionally and independently marked by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-10 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR 5 R 6 The substituents are replaced;

[0262] Or, R 2 R 7 The atoms bonded to it together form a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is optionally bonded by one or more atoms selected from C 1-6 Alkyl groups are substituted.

[0263] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 2 Each is independently selected from H, halogen, OH, C 1-6 Alkyl, C 2-6 alkenyl, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups and C 1-6hydroxyalkyl, the C 1-6 Alkyl, C 2-6 alkenyl, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups and C 1-6 Each hydroxyalkyl group is optionally and independently marked by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6- 10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR 5 R 6 The substituents are replaced;

[0264] Or, R 2 R 7 The atoms connected to it together form an imidazole group, which is optionally substituted with one or more methyl groups.

[0265] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 2 Each is independently selected from H, halogen, OH, C 1-4 Alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups and C 1-4 hydroxyalkyl, the C 1-4 Alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, C1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups and C 1-4 Each hydroxyalkyl group is optionally and independently marked by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C. 1-4 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-4 Haloalkyl, C 3-6 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-6 membered heterocyclic, C 1-4 Alkoxy, -OC 6-10 Aryl, -SC 6- 10 Aryl, -S(=O)-C 1-4 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-4 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)-C 1-4 Alkyl group, -OC(=O)-C 1-4 Alkyl, -C(=O)-OC 1-4 Substituents of alkyl groups;

[0266] Or, R 2 R 7 The atoms connected to it together form an imidazole group, which is optionally substituted with one or more methyl groups.

[0267] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 2 For H and halogens (e.g., F, Cl, Br, and I); or, R 2 R 7 The atoms connected to it together form an imidazole group, which is optionally substituted with one or more methyl groups.

[0268] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 2 For H and F; or, R 2 R 7 The atoms connected to it together form an imidazole group, which is optionally substituted with one or more methyl groups.

[0269] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R2 For H.

[0270] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 3 Each is independently selected from H, halogens, CN, OH, NO2, -NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, carboxyl, C 1- 6-Hydroalkyl, C 1-6 Halogenated alkoxy groups, oxo groups, thio groups, C 3-10 cycloalkyl, -OC 3-10 Cycloalkyl and 3-10 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, carboxyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, oxo groups, thio groups, C 3-10 cycloalkyl, -OC 3-10 The cycloalkyl group and the 3-10 membered heterocyclic group are each independently and optionally surrounded by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-10 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl groups, -C(=O)-OH, NO2, and -NR 5 R 6 The substituents are replaced by the substituents.

[0271] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 3Each is independently selected from H, halogens, CN, OH, NO2, -NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, carboxyl, C 1- 6-Hydroalkyl, C 1-6 Halogenated alkoxy groups, oxo groups, thio groups, C 3-8 cycloalkyl, -OC 3-8 Cycloalkyl and 3-8 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, carboxyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, oxo groups, thio groups, C 3-8 cycloalkyl, -OC 3-8 The cycloalkyl group and the 3-8 membered heterocyclic group are each independently and optionally surrounded by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3- 8-cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl groups, -C(=O)-OH, NO2, and -NR 5 R 6 The substituents are replaced by the substituents.

[0272] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 3 Each is independently selected from H, halogens, CN, OH, NO2, and C. 1-6 Alkyl, C 1-6 Alkoxy, carboxyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, oxo groups, thio groups, C3-8 cycloalkyl, -OC 3-8 Cycloalkyl and 3-8 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, carboxyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, oxo groups, thio groups, C 3-8 cycloalkyl, -OC 3-8 The cycloalkyl group and the 3-8 membered heterocyclic group are each independently and optionally surrounded by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 It is replaced by alkyl groups or -C(=O)-OH substituents.

[0273] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 3 Each is independently selected from H, halogens, CN, OH, NO2, and C. 1-4 Alkyl, C 1-6 Alkoxy, carboxyl, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, oxo groups, thio groups, C 3-6 cycloalkyl, -OC 3-8 Cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-4 Alkyl, C 1-4 Alkoxy, carboxyl, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, oxo groups, thio groups, C 3-6 cycloalkyl, -OC 3-6 The cycloalkyl group and the 3-6 membered heterocyclic group are each independently and optionally surrounded by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C.1-4 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-4 Haloalkyl, C 3-6 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-6 membered heterocyclic, C 1-4 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-4 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-4 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)-C 1-4 Alkyl group, -OC(=O)-C 1-4 Alkyl, -C(=O)-OC 1-4 It is replaced by alkyl groups or -C(=O)-OH substituents.

[0274] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 3 Each is independently selected from H and halogens, such as R. 3 Each is independently selected from H, F, Cl, and Br, preferably R. 3 They are each independently selected from H and Cl.

[0275] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 3 Each is independently selected from halogens, such as R 3 Each is independently selected from F, Cl, and Br, preferably R. 3 It is Cl.

[0276] In some embodiments, the present invention provides a compound of formula (I), wherein R 4 Selected from H, deuterium, halogen, oxo group, thio group, CN, OR 7 SR 7 S(=O)R 7 S(=O)2R 7 NO2, -NR 5 R 6 -NR 7 S(=O)2R c -S(=O)2N R 5 R 6 -C(=O)R 7 -C(=O)OR 7-C(=O)NR 5 R 6 -OC(=O)NR 5 R 6 -NR 7 C(=O)2R c -NR 7 C(=O)2NR 5 R 6 -NR 7 C(=O)2OR c C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3- 10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl and 3-12 membered heterocyclic, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, C 2- 6-alkenyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3-10 cycloalkyl, C 6-10 The aryl, 5-10-membered heteroaryl, and 3-12-membered heterocyclic groups are each independently and optionally bound by one or more elements selected from H, halogen, OH, CN, -COOH, C. 1- 6-alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-10 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0277] Two Rs 4 The atoms connected to it together form C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more elements selected from H, halogen, OH, CN, -NR. 5 R 6Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OC 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Substituents of aryl and 5-10 heteroaryl groups.

[0278] In some embodiments, the present invention provides a compound of formula (I), wherein R 4 Selected from H, deuterium, halogen, oxo group, thio group, CN, OR 7 SR 7 S(=O)R 7 S(=O)2R 7 NO2, -NR 5 R 6 -NR 7 S(=O)2R c -S(=O)2N R 5 R 6 -C(=O)R 7 -C(=O)OR 7 -C(=O)NR 5 R 6 -OC(=O)NR 5 R 6 -NR 7 C(=O)2R c -NR 7 C(=O)2NR 5 R 6 -NR 7 C(=O)2OR c C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3- 10 cycloalkyl, C 6-10 aryl, 3-12 membered heterocyclic groups and 5-10 membered heteroaryl groups containing 2-3 heteroatoms, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3-10 cycloalkyl, C 6-10Aryl, 3-12 membered heterocyclic groups, and 5-10 membered heteroaryl groups containing 2-3 heteroatoms are each independently and optionally bonded by one or more elements selected from H, halogen, OH, CN, -COOH, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-10 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0279] Two Rs 4 The atoms connected to it together form C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl containing 2-3 heteroatoms, wherein the C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group containing 2-3 heteroatoms are each independently and optionally bonded by one or more atoms selected from H, halogen, OH, CN, -NR. 5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OC 3- 10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Substituents of aryl and 5-10 heteroaryl groups.

[0280] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from H, deuterium, halogen, oxo group, thio group, CN, OR 7 SR 7 S(=O)R 7 S(=O)2R 7 NO2, -NR 5 R 6 -NR 7 S(=O)2R c -S(=O)2NR 5 R6 -C(=O)R 7 -C(=O)OR 7 -C(=O)NR 5 R 6 -OC(=O)NR 5 R 6 -NR 7 C(=O)2R c -NR 7 C(=O)2NR 5 R 6 -NR 7 C(=O)2OR c C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, C 3-8 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl and 3-10 membered heterocyclic, wherein the C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 alkenyl, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, C 3- 8-cycloalkyl, C 6-10 The aryl, 5-10-membered heteroaryl, and 3-10-membered heterocyclic groups are each independently and optionally bound by one or more groups selected from H, halogen, OH, CN, -COOH, oxo, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3- 8-cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0281] Two Rs 4 The atoms connected to it together form C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more elements selected from H, halogen, OH, CN, -NR. 5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 3-8 cycloalkyl, -OC 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Substituents of aryl and 5-10 heteroaryl groups.

[0282] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from H, deuterium, halogen, oxo group, thio group, CN, OR 7 SR 7 S(=O)R 7 S(=O)2R 7 NO2, -NR 5 R 6 -NR 7 S(=O)2R c -S(=O)2NR 5 R 6 -C(=O)R 7 -C(=O)OR 7 -C(=O)NR 5 R 6 -OC(=O)NR 5 R 6 -NR 7 C(=O)2R c -NR 7 C(=O)2NR 5 R 6 -NR 7 C(=O)2OR c C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, C 3-8 cycloalkyl, C 6-10 aryl, 3-10 membered heterocyclic groups, and 5-10 membered heteroaryl groups containing 2-3 heteroatoms, wherein the C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 alkenyl, C1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, C 3-8 cycloalkyl, C 6-10 Aryl, 3-10 membered heterocyclic groups, and 5-10 membered heteroaryl groups containing 2-3 heteroatoms are each independently and optionally bonded by one or more groups selected from H, halogen, OH, CN, -COOH, oxo, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, C 1- 6-Hydroalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0283] Two Rs 4 The atoms connected to it together form C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl containing 2-3 heteroatoms, wherein the C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group containing 2-3 heteroatoms are each independently and optionally bonded by one or more atoms selected from H, halogen, OH, CN, -NR. 5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 3-8 cycloalkyl, -OC 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Substituents of aryl and 5-10 heteroaryl groups.

[0284] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 65-10-membered heteroaryl and 3-10-membered heterocyclic group, wherein each of the 5-10-membered heteroaryl and 3-10-membered heterocyclic group is optionally and independently composed of one or more groups selected from oxo, OH, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0285] Two Rs 4 The atoms bonded to it together form a 5-10 membered heteroaryl or a 3-10 membered heterocyclic group, wherein the 5-10 membered heteroaryl and the 3-10 membered heterocyclic group are optionally composed of one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0286] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 3-10 membered heterocyclic groups and 5-10 membered heteroaryl groups containing 2-3 heteroatoms, wherein the 3-10 membered heterocyclic group and the 5-10 membered heteroaryl group containing 2-3 heteroatoms are each optionally and independently constituting one or more groups selected from oxo groups, OH groups, C groups, etc. 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0287] Two Rs 4 The atoms bonded to it together form a 3-10 membered heterocyclic group or a 5-10 membered heteroaryl group containing 2-3 heteroatoms, wherein the 3-10 membered heterocyclic group and the 5-10 membered heteroaryl group containing 2-3 heteroatoms are optionally bonded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0288] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 5-10-membered heteroaryl and 3-8-membered heterocyclic group, wherein each of the 5-10-membered heteroaryl and 3-8-membered heterocyclic group is optionally and independently composed of one or more groups selected from oxo, OH, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-10 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0289] Two Rs 4 The atoms bonded to it together form a 5-10 membered heteroaryl or a 3-10 membered heterocyclic group, wherein the 5-10 membered heteroaryl and the 3-10 membered heterocyclic group are optionally composed of one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0290] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 3-8 membered heterocyclic groups and 5-10 membered heteroaryl groups containing 2-3 heteroatoms, wherein the 3-8 membered heterocyclic group and the 5-10 membered heteroaryl group containing 2-3 heteroatoms are each optionally and independently constituting one or more groups selected from oxo groups, OH groups, C groups, etc. 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-10 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0291] Two Rs 4The atoms bonded to it together form a 3-10 membered heterocyclic group or a 5-10 membered heteroaryl group containing 2-3 heteroatoms, wherein the 3-10 membered heterocyclic group and the 5-10 membered heteroaryl group containing 2-3 heteroatoms are optionally bonded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0292] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 5-6-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-6-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from oxo, OH, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0293] Two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl or a 3-8 membered heterocyclic group, wherein the 5-6 membered heteroaryl and the 3-8 membered heterocyclic group are optionally bonded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0294] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 3-6 membered heterocyclic groups and 5-6 membered heteroaryl groups containing 2-3 heteroatoms, wherein the 3-6 membered heterocyclic group and the 5-6 membered heteroaryl group containing 2-3 heteroatoms are each optionally and independently constituting one or more groups selected from oxo groups, OH groups, C groups, C groups, etc. 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC3- 8-cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0295] Two Rs 4 The atoms bonded to it together form a 3-8 membered heterocyclic group or a 5-6 membered heteroaryl group containing 2-3 heteroatoms, wherein the 3-8 membered heterocyclic group and the 5-6 membered heteroaryl group containing 2-3 heteroatoms are optionally bonded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0296] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 5-6-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-6-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from oxo, OH, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 cycloalkyl, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0297] Two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl or a 3-6 membered heterocyclic group, wherein the 5-6 membered heteroaryl and the 3-6 membered heterocyclic group are optionally composed of one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0298] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 3-6 membered heterocyclic groups and 5-6 membered heteroaryl groups containing 2-3 heteroatoms, wherein the 3-6 membered heterocyclic group and the 5-6 membered heteroaryl group containing 2-3 heteroatoms are each optionally and independently constituting one or more groups selected from oxo groups, OH groups, C groups, C groups, etc.1-4 Alkyl, C 1-4 Alkoxy, C 3-6 cycloalkyl, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, -OC 3- 8-cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0299] Two Rs 4 The atoms connected thereto form a 3-6 membered heterocyclic group or a 5-6 membered heteroaryl group containing 2-3 heteroatoms, wherein the 3-6 membered heterocyclic group and the 5-6 membered heteroaryl group containing 2-3 heteroatoms are optionally separated by one or more atoms selected from -NR. 5 R 6 Substituents of oxy groups.

[0300] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from methyl, NH2, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, oxazolyl, isoxazolyl, triazine, pyrimidinyl, pyridinyl, pyrazinyl, triazole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, -NH-pyrimidinyl-CF3, The following are listed: -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, oxazolyl, isoxazolyl, triazine, pyrimidinyl, pyridinyl, pyrazinyl, triazole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3. Optionally, it may be independently substituted by one or more substituents selected from CH3, NH2, -NH-CH3, -NH-cyclopropyl, -NH-pyridyl-CH3, -NH-pyridyl-cyclopropyl, -NH-pyridyl-cyclobutyl, -NH-pyridyl-CF3, methoxy, trifluoromethoxy, -O-cyclopropyl, and triazole; and / or,

[0301] Two Rs 4 The atoms connected to it together form a 5-6 membered heteroaryl or a 3-6 membered heterocyclic group, wherein each of the 5-6 membered heteroaryl and the 3-6 membered heterocyclic group is optionally and independently replaced by one or more groups selected from oxo groups and -NH2.

[0302] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from methyl, NH2, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, oxazolyl, isoxazolyl, triazine, pyrimidinyl, pyrazinyl, triazole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, -NH-pyrimidinyl-CF3, The following groups are mentioned: -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, oxazolyl, isoxazolyl, triazine, pyrimidinyl, pyrazinyl, triazole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, -NH-pyrimidinyl-CF3. Optionally, it may be independently substituted by one or more substituents selected from CH3, NH2, -NH-CH3, -NH-cyclopropyl, -NH-pyridyl-CH3, -NH-pyridyl-cyclopropyl, -NH-pyridyl-cyclobutyl, -NH-pyridyl-CF3, methoxy, trifluoromethoxy, -O-cyclopropyl, and triazole; and / or,

[0303] Two Rs 4 The atoms connected to it together form a 3-6 membered heterocyclic group or a 5-6 membered heteroaryl group containing 2-3 heteroatoms, wherein the 5-6 membered heteroaryl group and the 3-6 membered heterocyclic group are each optionally and independently replaced by one or more groups selected from oxo groups and -NH2.

[0304] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 4 Selected from methyl, NH2, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, Pyrimidinyl group substituted with NH2, pyrimidinyl group substituted with CH3, pyrimidinyl group substituted with cyclopropyl, pyrimidinyl group substituted with cyclobutyl, pyrimidinyl group substituted with trifluoromethoxy, pyridinyl group substituted with methoxy, pyridinyl group substituted with trifluoromethoxy, pyridinyl group substituted with -O-cyclopropyl, pyrazinyl group substituted with -NH-CH3, pyrazinyl group substituted with -NH-cyclopropyl, pyrazinyl group substituted with -NH2, oxazolyl group substituted with -NH2, isoxazolyl group substituted with -NH2 Triazine group replaced by -NH2, Triazolyl, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl and -NH-pyrimidinyl-CF3; and / or,

[0305] Two Rs 4 The atoms connected to it form together

[0306] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 4 Selected from methyl, NH2, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, Pyrimidinyl group substituted with NH2, pyrimidinyl group substituted with CH3, pyrimidinyl group substituted with cyclopropyl, pyrimidinyl group substituted with cyclobutyl, pyrimidinyl group substituted with trifluoromethoxy, pyrazinyl group substituted with -NH-CH3, pyrazinyl group substituted with -NH-cyclopropyl, pyrazinyl group substituted with -NH2, oxazolyl group substituted with -NH2, isoxazolyl group substituted with -NH2 Triazine group replaced by -NH2, Triazolyl, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl and -NH-pyrimidinyl-CF3; and / or,

[0307] Two Rs 4 The atoms connected to it form together

[0308] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from H, deuterium, halogen, oxo group, thio group, CN, OR 7 SR 7 S(=O)R 7 S(=O)2R 7 NO2, -NR 5 R 6 -NR 7 S(=O)2R c -S(=O)2NR 5 R 6 -C(=O)R 7 -C(=O)OR 7 -C(=O)NR 5 R 6 -OC(=O)NR 5 R 6 -NR 7 C(=O)2R c -NR 7 C(=O)2NR5 R 6 -NR 7 C(=O)2OR c C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, C 3-8 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl and 3-10 membered heterocyclic, wherein the C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 alkenyl, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, C 3- 8-cycloalkyl, C 6-10 The aryl, 5-10 heteroaryl, and 3-10 heterocyclic groups are each independently and optionally bound by one or more elements selected from H, halogen, OH, CN, -COOH, C. 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0309] Two Rs 4 The atoms connected to it together form C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more elements selected from H, halogen, OH, CN, -NR. 5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 3-8 cycloalkyl, -OC 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C6-10 Substituents of aryl and 5-10 heteroaryl groups.

[0310] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from H, deuterium, halogen, oxo group, thio group, CN, OR 7 SR 7 S(=O)R 7 S(=O)2R 7 NO2, -NR 5 R 6 -NR 7 S(=O)2R c -S(=O)2NR 5 R 6 -C(=O)R 7 -C(=O)OR 7 -C(=O)NR 5 R 6 -OC(=O)NR 5 R 6 -NR 7 C(=O)2R c -NR 7 C(=O)2NR 5 R 6 -NR 7 C(=O)2OR c C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, C 3-8 cycloalkyl, C 6-10 aryl, 3-10 membered heterocyclic groups, and 5-10 membered heteroaryl groups containing 2-3 heteroatoms, wherein the C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 alkenyl, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, C 3-8 cycloalkyl, C 6-10 Aryl, 3-10 membered heterocyclic groups, and 5-10 membered heteroaryl groups containing 2-3 heteroatoms are each independently and optionally bonded by one or more elements selected from H, halogen, OH, CN, -COOH, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0311] Two Rs 4 The atoms connected to it together form C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl containing 2-3 heteroatoms, wherein the C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group containing 2-3 heteroatoms are each independently and optionally bonded by one or more atoms selected from H, halogen, OH, CN, -NR. 5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 3-8 cycloalkyl, -OC 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Substituents of aryl and 5-10 heteroaryl groups.

[0312] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from H, deuterium, halogen, oxo group, thio group, CN, OR 7 SR 7 S(=O)R 7 S(=O)2R 7 NO2, -NR 5 R 6 -NR 7 S(=O)2R c -S(=O)2NR 5 R 6 -C(=O)R 7 -C(=O)OR 7 -C(=O)NR 5 R 6 -OC(=O)NR 5 R 6 -NR 7 C(=O)2Rc -NR 7 C(=O)2NR 5 R 6 -NR 7 C(=O)2OR c C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, C 3-8 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl and 3-10 membered heterocyclic, wherein the C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 alkenyl, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, C 3- 8-cycloalkyl, C 6-10 The aryl, 5-10 heteroaryl, and 3-10 heterocyclic groups are each independently and optionally bound by one or more elements selected from H, halogen, OH, CN, -COOH, C. 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0313] Or, two Rs 4 The atoms connected to it together form C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more elements selected from H, halogen, OH, CN, -NR. 5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 3-8cycloalkyl, -OC 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Substituents of aryl and 5-10 heteroaryl groups.

[0314] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from H, deuterium, halogen, oxo group, thio group, CN, OR 7 SR 7 S(=O)R 7 S(=O)2R 7 NO2, -NR 5 R 6 -NR 7 S(=O)2R c -S(=O)2NR 5 R 6 -C(=O)R 7 -C(=O)OR 7 -C(=O)NR 5 R 6 -OC(=O)NR 5 R 6 -NR 7 C(=O)2R c -NR 7 C(=O)2NR 5 R 6 -NR 7 C(=O)2OR c C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, C 3-8 cycloalkyl, C 6-10 aryl, 3-10 membered heterocyclic groups, and 5-10 membered heteroaryl groups containing 2-3 heteroatoms, wherein the C 1-4 Alkyl, C 1-4 Alkoxy, C 2-6 alkenyl, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, C 3-8 cycloalkyl, C 6-10 Aryl, 3-10 membered heterocyclic groups, and 5-10 membered heteroaryl groups containing 2-3 heteroatoms are each independently and optionally bonded by one or more elements selected from H, halogen, OH, CN, -COOH, C 1-6 Alkyl, C 2-6 alkenyl, C1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0315] Or, two Rs 4 The atoms connected to it together form C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl containing 2-3 heteroatoms, wherein the C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group containing 2-3 heteroatoms are each independently and optionally bonded by one or more atoms selected from H, halogen, OH, CN, -NR. 5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 3-8 cycloalkyl, -OC 3- 8-cycloalkyl, 3-10 membered heterocyclic, C 6-10 Substituents of aryl and 5-10 heteroaryl groups.

[0316] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein, in the compound, R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 5-10-membered heteroaryl and 3-10-membered heterocyclic group, wherein each of the 5-10-membered heteroaryl and 3-10-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0317] Two Rs 4 The atoms bonded to it together form a 5-10 membered heteroaryl or a 3-10 membered heterocyclic group, wherein the 5-10 membered heteroaryl and the 3-10 membered heterocyclic group are optionally composed of one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0318] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein, in the compound, R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 3-10 membered heterocyclic groups and 5-10 membered heteroaryl groups containing 2-3 heteroatoms, wherein the 3-10 membered heterocyclic group and the 5-10 membered heteroaryl group containing 2-3 heteroatoms are each optionally and independently composed of one or more components selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0319] Two Rs 4 The atoms bonded to it together form a 3-10 membered heterocyclic group or a 5-10 membered heteroaryl group containing 2-3 heteroatoms, wherein the 3-10 membered heterocyclic group and the 5-10 membered heteroaryl group containing 2-3 heteroatoms are optionally bonded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0320] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 5-10-membered heteroaryl and 3-8-membered heterocyclic group, wherein each of the 5-10-membered heteroaryl and 3-8-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-10 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0321] Two Rs 4 The atoms bonded to it together form a 5-10 membered heteroaryl or a 3-10 membered heterocyclic group, wherein the 5-10 membered heteroaryl and the 3-10 membered heterocyclic group are optionally composed of one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0322] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 3-8 membered heterocyclic groups and 5-10 membered heteroaryl groups containing 2-3 heteroatoms, wherein the 3-8 membered heterocyclic group and the 5-10 membered heteroaryl group containing 2-3 heteroatoms are each optionally and independently composed of one or more components selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-10 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0323] Two Rs 4 The atoms bonded to it together form a 3-10 membered heterocyclic group or a 5-10 membered heteroaryl group containing 2-3 heteroatoms, wherein the 3-10 membered heterocyclic group and the 5-10 membered heteroaryl group containing 2-3 heteroatoms are optionally bonded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0324] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from methyl, NH2, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyridinyl, pyrazinyl, triazole, oxazolyl, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3, wherein -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyridinyl, pyrazinyl, triazole, oxazolyl, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3 are optionally and independently composed of one or more compounds selected from CH3, NH2, -NH-CH3, -NH-cyclopropyl, -NH-pyridinyl-CH3, -NH-pyridinyl-cyclopropyl, -NH-pyridinyl-cyclobutyl, -NH-pyridinyl-CF3, methoxy, trifluoromethoxy, -O-cyclopropyl, triazole, and Substituents are replaced by; and / or,

[0325] Two Rs 4 The atoms connected to it together form a 5-10 membered heteroaryl or a 3-10 membered heterocyclic group, wherein each of the 5-10 membered heteroaryl and the 3-10 membered heterocyclic group is optionally and independently replaced by one or more substituents selected from oxo groups and -NH2.

[0326] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from methyl, NH2, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyrazinyl, triazole, oxazolyl, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3, wherein -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyrazinyl, triazole, oxazolyl, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3 are optionally and independently composed of one or more compounds selected from CH3, NH2, -NH-CH3, -NH-cyclopropyl, -NH-pyridinyl-CH3, -NH-pyridinyl-cyclopropyl, -NH-pyridinyl-cyclobutyl, -NH-pyridinyl-CF3, methoxy, trifluoromethoxy, -O-cyclopropyl, triazole, and Substituents are replaced by; and / or,

[0327] Two Rs 4The atoms connected thereto form a 3-10 membered heterocyclic group or a 5-10 membered heteroaryl group containing 2-3 heteroatoms, wherein the 3-10 membered heterocyclic group and the 5-10 membered heteroaryl group containing 2-3 heteroatoms are each optionally and independently replaced by one or more substituents selected from oxo groups and -NH2.

[0328] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from methyl, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, oxazolyl,

[0329] And / or,

[0330] Two Rs 4 The atoms connected to it form together

[0331] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from methyl, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, oxazolyl,

[0332] And / or,

[0333] Two Rs 4 The atoms connected to it form together

[0334] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5 R 6 -C(=O)NR 5 R 6 5-10-membered heteroaryl and 3-10-membered heterocyclic group, wherein each of the 5-10-membered heteroaryl and 3-10-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Halogenated alkyl groups, -OC 3-8 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0335] Or, two Rs 4 The atoms bonded to it together form a 5-10 membered heteroaryl group, wherein the 5-10 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0336] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5 R 6 -C(=O)NR 5 R 6 3-10 membered heterocyclic groups and 5-10 membered heteroaryl groups containing 2-3 heteroatoms, wherein the 3-10 membered heterocyclic group and the 5-10 membered heteroaryl group containing 2-3 heteroatoms are each optionally and independently composed of one or more components selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Halogenated alkyl groups, -OC 3-8 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0337] Or, two Rs 4 The atoms bonded to it together form a 5-10 membered heteroaryl group containing 2-3 heteroatoms, wherein the 5-10 membered heteroaryl group containing 2-3 heteroatoms is optionally surrounded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0338] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5 R 6 -C(=O)NR 5 R 6 5-10-membered heteroaryl and 3-8-membered heterocyclic group, wherein each of the 5-10-membered heteroaryl and 3-8-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Halogenated alkyl groups, -OC 3-10 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0339] Or, two Rs4 The atoms bonded to it together form a 5-10 membered heteroaryl group, wherein the 5-10 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0340] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5 R 6 -C(=O)NR 5 R 6 3-8 membered heterocyclic groups and 5-10 membered heteroaryl groups containing 2-3 heteroatoms, wherein the 3-8 membered heterocyclic group and the 5-10 membered heteroaryl group containing 2-3 heteroatoms are each optionally and independently composed of one or more components selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Halogenated alkyl groups, -OC 3-10 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0341] Or, two Rs 4 The atoms bonded to it together form a 5-10 membered heteroaryl group containing 2-3 heteroatoms, wherein the 5-10 membered heteroaryl group containing 2-3 heteroatoms is optionally surrounded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0342] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 5-6-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-6-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0343] Two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl or a 3-8 membered heterocyclic group, wherein the 5-6 membered heteroaryl and the 3-8 membered heterocyclic group are optionally bonded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0344] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 3-6 membered heterocyclic groups and 5-6 membered heteroaryl groups containing 2-3 heteroatoms, wherein the 3-6 membered heterocyclic group and the 5-6 membered heteroaryl group containing 2-3 heteroatoms are each optionally and independently composed of one or more components selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0345] Two Rs 4 The atoms connected thereto form a 3-8 membered heterocyclic group or a 5-6 membered heteroaryl group containing 2-3 heteroatoms, wherein the 3-8 membered heterocyclic group or the 5-6 membered heteroaryl group containing 2-3 heteroatoms is optionally surrounded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0346] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5 R 6 -C(=O)NR 5 R 6 5-6-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-6-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 1-6 Halogenated alkyl groups, -OC 3-8 cycloalkyl, -NR 5 R6 The substituents are replaced;

[0347] Or, two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0348] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5 R 6 -C(=O)NR 5 R 6 3-6 membered heterocyclic groups and 5-6 membered heteroaryl groups containing 2-3 heteroatoms, wherein the 3-6 membered heterocyclic group and the 5-6 membered heteroaryl group containing 2-3 heteroatoms are each optionally and independently composed of one or more components selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 1-6 Halogenated alkyl groups, -OC 3-8 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0349] Or, two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl group containing 2-3 heteroatoms, wherein the 5-6 membered heteroaryl group containing 2-3 heteroatoms is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0350] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 5-6-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-6-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 cycloalkyl, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5R 6 Substituents are replaced by; and / or,

[0351] Two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl or a 3-6 membered heterocyclic group, wherein the 5-6 membered heteroaryl and the 3-6 membered heterocyclic group are optionally composed of one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0352] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 3-6 membered heterocyclic groups and 5-6 membered heteroaryl groups containing 2-3 heteroatoms, wherein the 3-6 membered heterocyclic group and the 5-6 membered heteroaryl group containing 2-3 heteroatoms are each optionally and independently composed of one or more components selected from C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 cycloalkyl, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0353] Two Rs 4 The atoms connected thereto form a 3-6 membered heterocyclic group or a 5-6 membered heteroaryl group containing 2-3 heteroatoms, wherein the 3-6 membered heterocyclic group or the 5-6 membered heteroaryl group containing 2-3 heteroatoms is optionally surrounded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0354] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5 R 6 -C(=O)NR 5 R 6 5-6-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-6-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 cycloalkyl, C 1-4Halogenated alkyl groups, -OC 3-8 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0355] Or, two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0356] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5 R 6 -C(=O)NR 5 R 6 3-6 membered heterocyclic groups and 5-6 membered heteroaryl groups containing 2-3 heteroatoms, wherein the 3-6 membered heterocyclic group and the 5-6 membered heteroaryl group containing 2-3 heteroatoms are each optionally and independently composed of one or more components selected from C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 cycloalkyl, C 1-4 Halogenated alkyl groups, -OC 3-8 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0357] Or, two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl group containing 2-3 heteroatoms, wherein the 5-6 membered heteroaryl group containing 2-3 heteroatoms is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituents of oxy groups.

[0358] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5 R 6 -C(=O)NR 5 R 6 5-6-membered heteroaryl and 3-6-membered heterocyclic group; wherein the 5-6-membered heteroaryl and 3-6-membered heterocyclic group are each optionally and independently composed of one or more groups selected from C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 cycloalkyl, C 1-4 Halogenated alkoxy groups, -OC 3-8Substituents include cycloalkyl, -NH2, and oxo groups; in some embodiments, -C(=O)NR 5 R 6 Selected from -C(=O)NH2, -C(=O)NH-C 1-4 Alkyl, -C(=O)NH-3 to 6-membered cycloalkyl; in some embodiments, -C(=O)NR 5 R 6 Selected from -C(=O)NH2, -C(=O)NHCH3, -C(=O)NH-cyclopropyl.

[0359] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein two R 4 The atoms connected to it together form a 5-6 membered heteroaryl group, which is optionally replaced by one or more substituents selected from -NH2 and oxo groups.

[0360] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5 R 6 -C(=O)NR 5 R 6 3-6 membered heterocyclic groups and 5-6 membered heteroaryl groups containing 2-3 heteroatoms; wherein the 3-6 membered heterocyclic group and the 5-6 membered heteroaryl group containing 2-3 heteroatoms are each optionally and independently composed of one or more components selected from C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 cycloalkyl, C 1-4 Halogenated alkoxy groups, -OC 3-8 Substituents include cycloalkyl, -NH2, and oxo groups; in some embodiments, -C(=O)NR 5 R 6 Selected from -C(=O)NH2, -C(=O)NH-C 1-4 Alkyl, -C(=O)NH-3 to 6-membered cycloalkyl; in some embodiments, -C(=O)NR 5 R 6 Selected from -C(=O)NH2, -C(=O)NHCH3, -C(=O)NH-cyclopropyl.

[0361] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein two R 4The atoms connected to it together form a 5-6 membered heteroaryl group containing 2-3 heteroatoms, wherein the 5-6 membered heteroaryl group containing 2-3 heteroatoms is optionally replaced by one or more substituents selected from -NH2 and oxo groups.

[0362] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 5 R 6 and R 7 Each is independently selected from H, halogen, OH, CN, C 1-6 Alkyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-10 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR a R b -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR a R b The substituents are replaced by the substituents.

[0363] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 5 and R 6 Each is independently selected from H, halogen, OH, CN, C 1-6 Alkyl, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-8 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C6-10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR a R b -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR a R b The substituents are replaced by the substituents.

[0364] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 5 and R 6 Each is independently selected from H, halogen, C 1-6 Alkyl, C 3-8 cycloalkyl and 5-10-membered heteroaryl groups, wherein the C 1-6 Alkyl, C 3-8 The cycloalkyl group and the 5-10-membered heteroaryl group are each independently and optionally surrounded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6- 10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR a R b -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NRa R b The substituents are replaced by the substituents.

[0365] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 5 and R 6 Each is independently selected from H and C. 1-6 Alkyl, C 3-8 cycloalkyl and 5-10-membered heteroaryl groups, wherein the C 1-6 Alkyl, C 3- The 8-cycloalkyl group and the 5-10-membered heteroaryl group are each independently and optionally separated by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR a R b -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR a R b The substituents are replaced by the substituents.

[0366] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 5 and R 6 Each is independently selected from H, halogen, C 1-6 Alkyl, C 3-8 cycloalkyl and 5-10-membered heteroaryl groups, wherein the C 1-6 Alkyl, C 3-8 The cycloalkyl group and the 5-10 heteroaryl group are each independently and optionally separated by one or more groups selected from C. 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Substituents of cycloalkyl groups.

[0367] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 5 R 6 Each is independently selected from H, halogen, C 1-6 Alkyl, C 3-6 cycloalkyl and 5-6-membered heteroaryl, the C 1-6 Alkyl, C 3-6 The cycloalkyl group and the 5-6-membered heteroaryl group are each independently and optionally separated by one or more groups selected from C. 1-6 Alkyl, C 3-6 cycloalkyl, fluorinated C 1-6 Alkyl, Chlorinated C 1-6 Alkyl groups are substituted.

[0368] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 5 R 6 Each is independently selected from H, halogen, C 1-4 Alkyl, C 3-6 cycloalkyl and 5-6-membered heteroaryl, the C 1-4 Alkyl, C 3-6 The cycloalkyl group and the 5-6-membered heteroaryl group are each independently and optionally separated by one or more groups selected from C. 1-4 Alkyl, C 3-6 cycloalkyl, fluorinated C 1-4 Alkyl, Chlorinated C 1-4 Alkyl groups are substituted.

[0369] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 5 R 6 Each is independently selected from H, F, Cl, methyl, cyclopropyl, -pyrimidinyl-CH3, -pyrimidinyl-cyclopropyl, -pyrimidinyl-cyclobutyl, and -pyrimidinyl-CF3. In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 5 and R 6 Each is independently selected from H and C. 1-6 Alkyl, C 3-8 cycloalkyl and 5-10-membered heteroaryl groups, wherein the C 1-6 Alkyl, C 3-8 The cycloalkyl group and the 5-10 heteroaryl group are each independently and optionally separated by one or more groups selected from C. 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Substituents of cycloalkyl groups.

[0370] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 5 R 6 Each is independently selected from H and C. 1-6 Alkyl, C 3-6 cycloalkyl and 5-6-membered heteroaryl, the C 1-6 Alkyl, C 3-6 The cycloalkyl group and the 5-6-membered heteroaryl group are each independently and optionally separated by one or more groups selected from C. 1-6 Alkyl, C 3-6 cycloalkyl, fluorinated C 1- 6-alkyl, chloro-C 1-6 Alkyl groups are substituted.

[0371] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 5 R 6 Each is independently selected from H and C. 1-4 Alkyl, C 3-6 cycloalkyl and 5-6-membered heteroaryl, the C 1-4 Alkyl, C 3-6 The cycloalkyl group and the 5-6-membered heteroaryl group are each independently and optionally separated by one or more groups selected from C. 1-4 Alkyl, C 3-6 cycloalkyl, fluorinated C 1- 4-alkyl, chloro-C 1-4 Alkyl groups are substituted.

[0372] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 5 R 6 Each is independently selected from H, methyl, cyclopropyl, -pyrimidinyl-CH3, -pyrimidinyl-cyclopropyl, -pyrimidinyl-cyclobutyl and -pyrimidinyl-CF3.

[0373] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-6 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 5-10-membered heteroaryl and 3-8-membered heterocyclic group, wherein each of the 5-10-membered heteroaryl and 3-8-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-8 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0374] Two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituted by oxy groups;

[0375] R 5 and R 6 Each is independently selected from H and C. 1-6 Alkyl, C 3-8 cycloalkyl and 5-10-membered heteroaryl groups, wherein the C 1-6 Alkyl, C 3-8 The cycloalkyl group and the 5-10 heteroaryl group are each independently and optionally separated by one or more groups selected from C. 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl.

[0376] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5 R 6 -C(=O)NR 5 R 6 5-10-membered heteroaryl and 3-8-membered heterocyclic group, wherein each of the 5-10-membered heteroaryl and 3-8-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Halogenated alkyl groups, -OC 3-8 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0377] Or, two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituted by oxy groups;

[0378] R 5 and R 6Each is independently selected from H and C. 1-6 Alkyl, C 3-8 cycloalkyl and 5-10-membered heteroaryl groups, wherein the C 1-6 Alkyl, C 3-8 The cycloalkyl group and the 5-10 heteroaryl group are each independently and optionally separated by one or more groups selected from C. 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl.

[0379] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 5-10-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-10-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-6 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0380] Two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituted by oxy groups;

[0381] R 5 and R 6 Each is independently selected from H and C. 1-6 Alkyl, C 3-8 cycloalkyl and 5-10-membered heteroaryl groups, wherein the C 1-6 Alkyl, C 3-8 The cycloalkyl group and the 5-10 heteroaryl group are each independently and optionally separated by one or more groups selected from C. 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl.

[0382] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5R 6 -C(=O)NR 5 R 6 5-10-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-10-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Halogenated alkyl groups, -OC 3-6 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0383] Or, two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituted by oxy groups;

[0384] R 5 and R 6 Each is independently selected from H and C. 1-6 Alkyl, C 3-8 cycloalkyl and 5-10-membered heteroaryl groups, wherein the C 1-6 Alkyl, C 3-8 The cycloalkyl group and the 5-10 heteroaryl group are each independently and optionally separated by one or more groups selected from C. 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 Cycloalkyl.

[0385] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 5-6-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-6-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-6 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0386] Two Rs 4The atoms bonded to it together form a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituted by oxy groups;

[0387] R 5 R 6 Each is independently selected from H and C. 1-6 Alkyl, C 3-6 cycloalkyl and 5-6-membered heteroaryl, the C 1-6 Alkyl, C 3-6 The cycloalkyl group and the 5-6-membered heteroaryl group are each independently and optionally separated by one or more groups selected from C. 1-6 Alkyl, C 3-6 cycloalkyl, C 1-6 Fluoroalkyl, C 1-6 The substituents of the chloroalkyl group are replaced.

[0388] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5 R 6 -C(=O)NR 5 R 6 5-6-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-6-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 1-6 Halogenated alkyl groups, -OC 3-6 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0389] Or, two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituted by oxy groups;

[0390] R 5 R 6 Each is independently selected from H and C. 1-6 Alkyl, C 3-6 cycloalkyl and 5-6-membered heteroaryl, the C 1-6 Alkyl, C 3-6 The cycloalkyl group and the 5-6-membered heteroaryl group are each independently and optionally separated by one or more groups selected from C. 1-6 Alkyl, C 3-6 cycloalkyl, C1-6 Fluoroalkyl, C 1-6 The substituents of the chloroalkyl group are replaced.

[0391] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 5-6-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-6-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-6 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0392] Two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituted by oxy groups;

[0393] R 5 R 6 Each is independently selected from H, methyl, cyclopropyl, -pyrimidinyl-CH3, -pyrimidinyl-cyclopropyl, -pyrimidinyl-cyclobutyl, -pyrimidinyl-CF3 and pyrazolyl.

[0394] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 5-6-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-6-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-6 cycloalkyl, -NR5 R 6 Substituents are replaced by; and / or,

[0395] Two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituted by oxy groups;

[0396] R 5 R 6 Each is independently selected from H, methyl, cyclopropyl, -pyrimidinyl-CH3, -pyrimidinyl-cyclopropyl, -pyrimidinyl-cyclobutyl and -pyrimidinyl-CF3.

[0397] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5 R 6 -C(=O)NR 5 R 6 5-6-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-6-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 cycloalkyl, C 1-6 Halogenated alkyl groups, -OC 3-6 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0398] Or, two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituted by oxy groups;

[0399] R 5 R 6 Each is independently selected from H, methyl, cyclopropyl, -pyrimidinyl-CH3, -pyrimidinyl-cyclopropyl, -pyrimidinyl-cyclobutyl and -pyrimidinyl-CF3.

[0400] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R6 5-6-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-6-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 cycloalkyl, C 1-4 Halogenated alkoxy groups, C 1-4 Halogenated alkyl groups, -OC 3-6 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or,

[0401] Two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituted by oxy groups;

[0402] R 5 R 6 Each is independently selected from H, methyl, cyclopropyl, -pyrimidinyl-CH3, -pyrimidinyl-cyclopropyl, -pyrimidinyl-cyclobutyl and -pyrimidinyl-CF3.

[0403] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -NR 5 R 6 -C(=O)NR 5 R 6 5-6-membered heteroaryl and 3-6-membered heterocyclic group, wherein each of the 5-6-membered heteroaryl and 3-6-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 cycloalkyl, C 1-4 Halogenated alkyl groups, -OC 3-6 cycloalkyl, -NR 5 R 6 The substituents are replaced;

[0404] Or, two Rs 4 The atoms bonded to it together form a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is optionally bonded by one or more atoms selected from -NR 5 R 6 Substituted by oxy groups;

[0405] R 5 R 6Each is independently selected from H, methyl, cyclopropyl, -pyrimidinyl-CH3, -pyrimidinyl-cyclopropyl, -pyrimidinyl-cyclobutyl and -pyrimidinyl-CF3.

[0406] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from methyl, NH2, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyridyl, pyrazinyl, triazole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3, wherein -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyridyl, ... Pyrazinyl, triazole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3 may optionally be independently substituted by one or more substituents selected from CH3, NH2, -NH-CH3, -NH-cyclopropyl, -NH-pyridinyl-CH3, -NH-pyridinyl-cyclopropyl, -NH-pyridinyl-cyclobutyl, -NH-pyridinyl-CF3, methoxy, trifluoromethoxy, -O-cyclopropyl, and triazole; and / or,

[0407] Two Rs 4 The atoms connected to it together form 5-10 heteroaryl groups, each of which may be optionally and independently replaced by one or more substituents selected from oxo groups and -NH2.

[0408] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4Selected from methyl, NH2, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyrazinyl, triazole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3, wherein -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyrazinyl, ... Triazole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3 may optionally be independently substituted by one or more substituents selected from CH3, NH2, -NH-CH3, -NH-cyclopropyl, -NH-pyridinyl-CH3, -NH-pyridinyl-cyclopropyl, -NH-pyridinyl-cyclobutyl, -NH-pyridinyl-CF3, methoxy, trifluoromethoxy, -O-cyclopropyl, and triazole; and / or,

[0409] Two Rs 4 The atoms connected to it together form a 5-10 membered heteroaryl group containing 2-3 heteroatoms, each of which is optionally and independently replaced by one or more substituents selected from oxo groups and -NH2.

[0410] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 Selected from -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyridyl, pyrazinyl, triazole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3, wherein -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyridinyl, pyridyl, pyrazin ... The azino, triazole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3 may be optionally and independently substituted by one or more substituents selected from CH3, NH2, -NH-CH3, -NH-cyclopropyl, -NH-pyridinyl-CH3, -NH-pyridinyl-cyclopropyl, -NH-pyridinyl-cyclobutyl, -NH-pyridinyl-CF3, methoxy, trifluoromethoxy, -O-cyclopropyl, and triazole;

[0411] Or, two Rs 4 The atoms connected to it together form 5-10 heteroaryl groups, each of which may be optionally and independently replaced by one or more substituents selected from oxo groups and -NH2.

[0412] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 The groups selected are -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyrazinyl, triazole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3, wherein -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyrazinyl, triazole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3. The azole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl and -NH-pyrimidinyl-CF3 may be optionally and independently substituted by one or more substituents selected from CH3, NH2, -NH-CH3, -NH-cyclopropyl, -NH-pyridinyl-CH3, -NH-pyridinyl-cyclopropyl, -NH-pyridinyl-cyclobutyl, -NH-pyridinyl-CF3, methoxy, trifluoromethoxy, -O-cyclopropyl and triazole;

[0413] Or, two Rs 4 The atoms connected to it together form a 5-10 membered heteroaryl group containing 2-3 heteroatoms, each of which is optionally and independently replaced by one or more substituents selected from oxo groups and -NH2.

[0414] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 The group is selected from methyl, NH2, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyridyl, pyrazinyl, triazolyl, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3, wherein the pyrimidinyl, pyridinyl, and pyrazinyl groups are optionally and independently substituted by one or more substituents selected from CH3, NH2, cyclopropyl, cyclobutyl, trifluoromethoxy, -O-cyclopropyl, -NH-CH3, -NH-cyclopropyl, and methoxy; and / or,

[0415] Two Rs 4 The atoms connected to it together form 5-10 heteroaryl groups, each of which may be optionally and independently replaced by one or more substituents selected from oxo groups and -NH2.

[0416] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 The group is selected from methyl, NH2, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyrazinyl, triazolyl, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3, wherein the pyrimidinyl and pyrazinyl groups are optionally and independently substituted by one or more substituents selected from CH3, NH2, cyclopropyl, cyclobutyl, trifluoromethoxy, -O-cyclopropyl, -NH-CH3, -NH-cyclopropyl, and methoxy; and / or,

[0417] Two Rs 4 The atoms connected to it together form a 5-10 membered heteroaryl group containing 2-3 heteroatoms, each of which is optionally and independently replaced by one or more substituents selected from oxo groups and -NH2.

[0418] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4 The group is selected from -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyridinyl, pyrazinyl, triazolyl, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3, wherein the pyrimidinyl, pyridinyl, and pyrazinyl groups are optionally and independently substituted by one or more substituents selected from CH3, NH2, cyclopropyl, cyclobutyl, trifluoromethoxy, -O-cyclopropyl, -NH-CH3, -NH-cyclopropyl, and methoxy.

[0419] Or, two Rs 4 The atoms connected to it together form 5-10 heteroaryl groups, each of which may be optionally and independently replaced by one or more substituents selected from oxo groups and -NH2.

[0420] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, wherein R 4The group is selected from -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyrazinyl, triazolyl, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3, wherein the pyrimidinyl and pyrazinyl groups are optionally and independently substituted by one or more substituents selected from CH3, NH2, cyclopropyl, cyclobutyl, trifluoromethoxy, -O-cyclopropyl, -NH-CH3, -NH-cyclopropyl, and methoxy.

[0421] Or, two Rs 4 The atoms connected to it together form a 5-10 membered heteroaryl group containing 2-3 heteroatoms, each of which is optionally and independently replaced by one or more substituents selected from oxo groups and -NH2.

[0422] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 4 Selected from methyl, NH2, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl substituted with NH2, pyrimidinyl substituted with CH3, pyrimidinyl substituted with cyclopropyl, pyrimidinyl substituted with cyclobutyl, pyrimidinyl substituted with trifluoromethoxy, pyridinyl substituted with methoxy, pyridinyl substituted with trifluoromethoxy, pyridinyl substituted with -O-cyclopropyl, pyrazinyl substituted with -NH-CH3, pyrazinyl substituted with -NH-cyclopropyl, triazolyl, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3; and / or,

[0423] Two Rs 4 The atoms connected to it form together

[0424] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 4Selected from methyl, NH2, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl substituted with NH2, pyrimidinyl substituted with CH3, pyrimidinyl substituted with cyclopropyl, pyrimidinyl substituted with cyclobutyl, pyrimidinyl substituted with trifluoromethoxy, pyrazinyl substituted with -NH-CH3, pyrazinyl substituted with -NH-cyclopropyl, triazolyl, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3; and / or,

[0425] Two Rs 4 The atoms connected to it form together

[0426] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 4 Selected from -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl substituted with NH2, pyrimidinyl substituted with CH3, pyrimidinyl substituted with cyclopropyl, pyrimidinyl substituted with cyclobutyl, pyrimidinyl substituted with trifluoromethoxy, pyrimidinyl substituted with methoxy, pyrimidinyl substituted with trifluoromethoxy, pyrimidinyl substituted with -O-cyclopropyl, pyrazinyl substituted with -NH-CH3, pyrazinyl substituted with -NH-cyclopropyl, triazole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3;

[0427] Or, two Rs 4 The atoms connected to it form together

[0428] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 4 Selected from -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl substituted with NH2, pyrimidinyl substituted with CH3, pyrimidinyl substituted with cyclopropyl, pyrimidinyl substituted with cyclobutyl, pyrimidinyl substituted with trifluoromethoxy, pyrazinyl substituted with -NH-CH3, pyrazinyl substituted with -NH-cyclopropyl, triazole, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3;

[0429] Or, two Rs 4 The atoms connected to it form together

[0430] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 7 Each is independently selected from H, halogen, OH, CN, C 1-6 Alkyl, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-8 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-10 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6- 10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR a R b-C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR a R b The substituents are replaced by the substituents.

[0431] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 7 Each is independently selected from H, halogen, OH, CN, C 1-6 Alkyl, C 3-6 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-6 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 3-6 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-6 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-6 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6- 10 Aryl, -S(=O)-C1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR a R b -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR a R b The substituents are replaced by the substituents.

[0432] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 7 Each is independently selected from H, halogen, OH, CN, C 1-4 Alkyl, C 3-6 cycloalkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-6 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-4 Alkyl, C 3-6 cycloalkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-6 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Haloalkyl, C 3-6cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-6 membered heterocyclic, C 1-4 Alkoxy, -OC 6-10 Aryl, -SC 6- 10 Aryl, -S(=O)-C 1-4 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-4 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR a R b -C(=O)-C 1-4 Alkyl group, -OC(=O)-C 1-4 Alkyl, -C(=O)-OC 1-4 Alkyl, NO2 and -NR a R b The substituents are replaced by the substituents.

[0433] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 7 Each is independently selected from H, halogen, OH, CN, C 1-4 Alkyl, C 3-6 cycloalkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c 3-6 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-4 Alkyl, C 3-6 cycloalkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups, C 1-4 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c 3-6 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen (e.g., F, Cl, Br), OH, CN, C. 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4Haloalkyl, C 3-6 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-6 membered heterocyclic, C 1-4 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-4 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-4 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)-C 1-4 Alkyl group, -OC(=O)-C 1-4 Alkyl, -C(=O)-OC 1-4 Alkyl groups are substituted.

[0434] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 7 Each is independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy-C 1-4 Alkyl-, -C 1-4 Alkyl-CN, -C(=O)C 1- 4-alkyl, 3-6-membered heterocyclic groups (e.g., 3-6-membered heterocyclic groups containing N, O and / or S atoms) and 5-10-membered heteroaryl groups.

[0435] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 7 Each is independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy-C 1-4 Alkyl-, -C 1-4 Alkyl-CN, 3-6 membered heterocyclic groups (e.g., 3-6 membered heterocyclic groups containing N, O and / or S atoms), and 5-10 membered heteroaryl groups, preferably, R 7 It is selected from methyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, -CH2CH2-OCH3, -CH2-OCH3, oxecyclopropane, oxecyclobutane, oxecyclopentane and 5-6 membered heteroaryl (e.g. pyridyl).

[0436] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 7Each is independently selected from methyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, -CH2CH2-OCH3, -CH2-CN, -CH2-OCH3, oxecyclopropane, oxecyclobutane, oxecyclopentane, CH3(C=O)- and pyridyl.

[0437] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 7 Each is independently selected from methyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, -CH2CH2-OCH3, -CH2-CN, -CH2-OCH3, oxecyclopropane, oxecyclobutane, oxecyclopentane, and pyridyl.

[0438] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 7 Each is independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy-C 1-4 Alkyl, 3-6 membered heterocyclic groups (e.g., 3-6 membered heterocyclic groups containing N, O and / or S atoms), and 5-10 membered heteroaryl groups, preferably, R 7 It is selected from methyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, -CH2CH2-OCH3, -CH2-OCH3, oxecyclopropane, oxecyclobutane, oxecyclopentane and 5-6 membered heteroaryl (e.g. pyridyl).

[0439] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 7 Each is independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy-C 1-4 Alkyl, 3-6 membered heterocyclic groups (e.g., 3-6 membered heterocyclic groups containing N, O and / or S atoms), and 5-10 membered heteroaryl groups, preferably, R 7 The compounds are selected from methyl, trifluoroethyl, -CH2CH2-OCH3, oxetane, and 5-6 membered heteroaryl groups (e.g., pyridyl). In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 7 Each is independently selected from C 1-4 Alkyl groups and 5-10 heteroaryl groups, preferably, R 7 Selected from methyl and 5-6 heteroaryl groups, such as methyl and pyridyl.

[0440] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R 7 Each is independently selected from 5-10 heteroaryl groups, preferably, R 7 Selected from 5-6 heteroaryl groups, such as pyridyl.

[0441] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R a and R b Each is independently selected from H and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Heteroalkyl, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Heteroalkyl, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more elements selected from H, halogen, OH, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-8 Substituents of cycloalkyl groups.

[0442] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R a and R b Each is independently selected from H and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Heteroalkyl, C 3-6 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Heteroalkyl, C 3-6 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more elements selected from H, halogen, OH, C. 1-6 Alkyl, C 1-6Haloalkyl, C 1-6 Alkoxy, C 3-6 Substituents of cycloalkyl groups.

[0443] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R a and R b Each is independently selected from H and C. 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-4 Heteroalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl and 5-10 heteroaryl, the C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Haloalkyl, C 1-4 Heteroalkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more elements selected from H, halogen, OH, C. 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 3-6 Substituents of cycloalkyl groups.

[0444] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R c Selected from H, OH, halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-8 Cycloalkyl, 3-10 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C6-10 Aryl, 5-10 membered heteroaryl, 3-10 membered heterocyclic, C 1- 6-alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1- 6-alkyl, NO2 and -NR 5 R 6 The substituents are replaced by the substituents.

[0445] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R c Selected from H, OH, halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl, 3-8 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR 5 R 6 The substituents are replaced by the substituents.

[0446] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R c Selected from H, OH, halogens, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl and 5-10 heteroaryl, the C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-4 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-4 Haloalkyl, C 3-6 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-6 membered heterocyclic, C 1-4 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-4 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-4 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-4 Alkyl group, -OC(=O)-C 1-4 Alkyl, -C(=O)-OC 1-4 Alkyl, NO2 and -NR 5 R 6 The substituents are replaced by the substituents.

[0447] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A), wherein R c Selected from H, OH, halogens, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 Aryl and 5-10 heteroaryl, the C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups, C 3-6 cycloalkyl, 3-6 membered heterocyclic, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-4 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-4 Haloalkyl, C 3-6 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-6 membered heterocyclic, C 1-4 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-4 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-4 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)-C 1-4 Alkyl group, -OC(=O)-C 1-4 Alkyl, -C(=O)-OC 1-4 It is replaced by alkyl groups and NO2 substituents.

[0448] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1') and formula (I-1-A), wherein m and n are independently selected from 0, 1, 2 and 3; preferably, m and n are independently selected from 0, 1 and 2.

[0449] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1') and formula (I-1-A), wherein m and n are independently selected from 0 and 1; preferably, m and n are independently selected from 1.

[0450] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1') and formula (I-1-A), wherein m is 3.

[0451] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1') and formula (I-1-A), wherein p is selected from 0, 1, 2, 3, 4 and 5, preferably p is selected from 0, 1, 2 and 3.

[0452] In some embodiments, the present invention provides compounds of formula (I), formula (I-1), formula (I-1') and formula (I-1-A), wherein p is selected from 0, 1, 2, 3 and 4, preferably p is selected from 0, 1 and 2; preferably p is selected from 0 and 1.

[0453] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, or Selected from:

[0454] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, or Selected from:

[0455] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, or Selected from:

[0456] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, or Selected from:

[0457] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, or Selected from:

[0458] In some embodiments, the compounds of formula (I), formula (I-1), formula (I-1'), and formula (I-1-A) provided by the present invention, or Selected from:

[0459] In some embodiments, the compounds of formula (I), formula (I-1), and formula (I-1-A) provided by the present invention, or Selected from:

[0460] In some embodiments, the compounds of formula (I), formula (I-1), and formula (I-1-A) provided by the present invention, or Selected from:

[0461] In some embodiments, the compound has a structure as shown in formula (I-2):

[0462] Among them, R 1 R 2 R 3 R 4 And m is as defined above.

[0463] In some embodiments, the compound has a structure as shown in formula (I-3):

[0464] Among them, R 1 R 2 R 3 R 4 And m is as defined above.

[0465] In some embodiments, the compound has a structure as shown in formula (I-4):

[0466] Among them, R 1 R 2 R 3 R 4 X 3 X 5 As defined above, X, m, and n, are... 7 X 8 X9 X 10 Each is independently selected from N and CH.

[0467] In some embodiments, in the compounds of formula (I-4) provided by the present invention, X 3 and X 5 Independently selected from NR 7 And O, preferably, X 3 and X 5 It is independently selected from -N(CH3)- and O.

[0468] In some embodiments, in the compounds of formula (I-4) provided by the present invention, R 4 Independently selected from oxo groups, C 1-4 Alkyl groups and NH2, such as R 4 It is independently selected from methyl and NH2.

[0469] In some embodiments, the compound has a structure as shown in formula (I-5):

[0470] Among them, R 1 R 2 R 3 R 4 X 3 X 4 X 6 As defined above, X, m, and n, are... 7 X 8 X 9 X 10 Each is independently selected from N and CH, and q is selected from 0 and 1.

[0471] In some embodiments, in the compounds of formula (I-5) provided by the present invention, X 3 Selected from CR 5 R 6 And O, preferably, X 3 Selected from CH2 and O.

[0472] In some embodiments, in the compounds of formula (I-5) provided by the present invention, X 4 Selected from N, CR 5 R 6 And O, preferably, X 4 Selected from N, CH2 and O.

[0473] In some embodiments, in the compounds of formula (I-5) provided by the present invention, X 6 Selected from CR 5 R 6 And O, preferably, X 6 Selected from CH2 and O.

[0474] In some embodiments, in the compounds of formula (I-5) provided by the present invention, R 4 Independently selected from oxo groups, C 1-4 Alkyl groups and NH2.

[0475] In some embodiments, in the compounds of formula (I-5) provided by the present invention, X 9 Selected from N and CH.

[0476] In some embodiments, the compound is selected from:

[0477] In some embodiments, the compound of the present invention may optionally be substituted at a suitable position with one or more suitable substituents.

[0478] In the compounds of formula (I) of the present invention, the groups in all embodiments can be suitably selected and combined in any way to obtain different general formula ranges or specific embodiments. These ranges and embodiments are all within the scope of the present invention. The present invention covers compounds obtained by arbitrary combinations of the various embodiments.

[0479] Preparation method

[0480] Another object of the present invention is to provide a method for preparing the compounds of the present invention. For example, the present invention provides a method for preparing compounds of formula (I), which includes the following steps:

[0481] Among them, rings A and R 1 R 2 R 3 R 4 X 1 X 2 m and n are as defined above;

[0482] LG 1 This indicates the leaving group in the coupling reaction, such as chlorine, bromine, iodine, and trifluoromethane sulfonate.

[0483] LG 2 This indicates the leaving group in a coupling reaction, for example...

[0484] LG 3 Indicates leaving groups, such as chlorine, bromine, and

[0485] PG 1 This indicates an amino protecting group, selected from alkoxycarbonyl amino protecting groups, such as benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc), methoxycarbonyl (Fmoc), allyloxycarbonyl (Alloc), trimethylsilylethoxycarbonyl (Teoc), and methoxycarbonyl (or ethoxycarbonyl); and acyl amino protecting groups, such as phthaloyl (Pht), p-toluenesulfonyl (Tos), trifluoroacetyl (Tfa), and o-(p-nitro) Benzenesulfonyl (Ns), pivaloyl, benzoyl, tert-butoxycarbonyl, 9-fluorenmethoxycarbonyl, allyloxycarbonyl, trichloroethoxycarbonyl, trimethylsilylethoxycarbonyl, benzyloxycarbonyl, p-methylbenzenesulfonyl, p-nitrobenzenesulfonyl, tert-butyl, trifluoroacetyl, methoxycarbonyl, and ethoxycarbonyl; alkyl amino protecting groups, such as triphenylmethyl (Trt), 2,4-dimethoxybenzyl (Dmb), 4-methoxybenzyl (PMB), and benzyl (Bn);

[0486] Preferably, the amino protecting group is selected from benzyloxycarbonyl (Cbz), tert-butyloxycarbonyl (Boc) and phosphomethyloxycarbonyl (Fmoc), and is particularly preferred to be tert-butyloxycarbonyl;

[0487] (1) React compound I-1-1 with compound I-1-1-a to obtain compound I-1-2;

[0488] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from N,N-dimethylformamide, 1,4-dioxane, tetrahydrofuran, water, toluene and any combination thereof. Preferably, the organic solvent is selected from a mixture of 1,4-dioxane and water.

[0489] The reaction is carried out in the presence of a suitable metal catalyst, which is tris(dibenzylacetone)dipalladium, [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex, tetratriphenylphosphine palladium, palladium acetate, Pd(dtbpf)Cl2 and any combination thereof. Preferably, the metal catalyst is [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex.

[0490] The reaction is preferably carried out in the presence of a suitable base, which may be selected from potassium acetate, potassium carbonate, potassium phosphate, cesium carbonate and any combination thereof. Preferably, the base is selected from potassium carbonate.

[0491] The reaction is preferably carried out at a suitable temperature, preferably 20-150°C; the reaction is preferably carried out for a suitable time, for example 1-24 hours.

[0492] (2) React compound I-1-2 to obtain compound I-1-3;

[0493] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from N,N-dimethylformamide, tetrahydrofuran, dichloromethane, and any combination thereof. Preferably, the organic solvent is selected from dichloromethane.

[0494] The reaction is preferably carried out in the presence of a suitable acid, which may be selected from hydrochloric acid, sulfuric acid, trifluoroacetic acid, or any combination thereof, preferably trifluoroacetic acid; the reaction is preferably carried out at a suitable temperature, preferably -10 to 60°C; the reaction is preferably carried out for a suitable time, for example, 0.5 to 4 hours.

[0495] (3) Reduce compound I-1-3 to obtain compound I-1-4;

[0496] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from methanol, tetrahydrofuran, dichloromethane, and any combination thereof; preferably, the organic solvent is selected from methanol. The reaction is preferably carried out in the presence of a suitable reducing agent, which may be selected from sodium borohydride, lithium borohydride, potassium borohydride, and any combination thereof; preferably, the reducing agent is selected from sodium borohydride. The reaction is preferably carried out at a suitable temperature, preferably -10 to 60°C. The reaction is preferably carried out for a suitable time, for example, 0.5 to 4 hours.

[0497] (4) React compound I-1-4 with compound I-1-4-a to obtain compound I;

[0498] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from dichloromethane, 1,4-dioxane, tetrahydrofuran, chloroform, N,N-dimethylformamide, and any combination thereof. Preferably, the organic solvent is selected from dichloromethane. The reaction is preferably carried out in the presence of a suitable base, which may be selected from N,N-diisopropylethylamine, triethylamine, N-methylmorpholine, 1,8-diazobisspirocyclo[5.4.0]undec-7-ene, and any combination thereof. Preferably, the base is selected from triethylamine. The reaction is preferably carried out at a suitable temperature, which is preferably -10 to 40°C. The reaction is preferably carried out for a suitable time, for example, 0.5 to 4 hours.

[0499] Another object of the present invention is to provide a method for preparing the compounds of the present invention. For example, the present invention provides a method for preparing compounds of formula (I), which includes the following steps:

[0500] Among them, rings A and R 1 R2 R 3 R 4 X 1 X 2 LG 1 LG 3 PG 1 m and n are as defined above;

[0501] LG 4 This indicates the leaving group in a coupling reaction, for example...

[0502] (1) Compound I-1-1 and I-1-1-b were subjected to a decarboxylation coupling reaction to obtain compound I-1-5;

[0503] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from N,N-dimethylacetamide, tetrahydrofuran, and any combination thereof. Preferably, the organic solvent is selected from N,N-dimethylacetamide. The reaction is preferably carried out in the presence of a suitable nickel catalyst, which may be selected from ethylene glycol dimethyl ether nickel bromide or nickel chloride dimethoxyethane. Preferably, the nickel catalyst is selected from nickel chloride dimethoxyethane. The reaction is preferably carried out in the presence of a suitable ligand, which may be selected from 4,4'-di-tert-butyl-2,2'-dipyridine, pyridine-2-formamidinium, 5-methoxypicolinimidine hydrochloride, or 4,4'-di-tert-butyl-N-cyano. -[2,2'-Bipyridine]-6-formamidinium, preferably, the ligand is 5-methoxypicolinimidine hydrochloride; the reaction is preferably carried out in the presence of a suitable additive, which may be selected from tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium chloride, trifluoroacetic acid, trimethylchlorosilane and any combination thereof, preferably, the additive is selected from tetrabutylammonium iodide and trifluoroacetic acid; the reaction is preferably carried out in the presence of a suitable reducing agent, which may be selected from manganese powder and zinc powder, preferably, the reducing agent is selected from zinc powder; the reaction is preferably carried out at a suitable temperature, preferably 0-60°C; the reaction is preferably carried out for a suitable time, for example, 1-24 hours;

[0504] (2) React compound I-1-5 to obtain compound I-1-4;

[0505] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from N,N-dimethylformamide, tetrahydrofuran, dichloromethane, and any combination thereof, preferably dichloromethane; the reaction is preferably carried out in the presence of a suitable acid, which may be selected from hydrochloric acid, sulfuric acid, trifluoroacetic acid, and any combination thereof, preferably trifluoroacetic acid; the reaction is preferably carried out at a suitable temperature, preferably -10 to 60°C; the reaction is preferably carried out for a suitable time, for example, 0.5 to 4 hours.

[0506] (3) React compound I-1-4 with compound I-1-4-a to obtain compound I;

[0507] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from dichloromethane, 1,4-dioxane, tetrahydrofuran, chloroform, N,N-dimethylformamide, and any combination thereof. Preferably, the organic solvent is selected from dichloromethane. The reaction is preferably carried out in the presence of a suitable base, which may be selected from N,N-diisopropylethylamine, triethylamine, N-methylmorpholine, 1,8-diazobisspirocyclo[5.4.0]undec-7-ene, and any combination thereof. Preferably, the base is selected from triethylamine. The reaction is preferably carried out at a suitable temperature, which is preferably -10 to 40°C. The reaction is preferably carried out for a suitable time, for example, 0.5 to 4 hours.

[0508] Another object of the present invention is to provide a method for preparing the compounds of the present invention. For example, the present invention provides a method for preparing compounds of formula (I-2), which includes the following steps:

[0509] Among them, R 1 R 2 R 3 R 4 And m as defined above; X represents a halogen atom, including chlorine, bromine and iodine;

[0510] (1) Compound I-2-1 was subjected to a halogenation reaction to obtain compound I-2-2;

[0511] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from N,N-dimethylformamide, tetrahydrofuran, dichloromethane, and any combination thereof; preferably, the organic solvent is selected from dichloromethane. The reaction is preferably carried out in the presence of a suitable halogenating agent, which may be selected from N-chlorosuccinimide, N-bromosuccinimide, dibromohydantoin, bromine, N-iodosuccinimide, and any combination thereof; preferably, the halogenating agent is selected from bromine. The reaction is preferably carried out at a suitable temperature, preferably -10 to 80°C. The reaction is preferably carried out for a suitable time, for example, 1 to 24 hours.

[0512] (2) Compound I-2-2 and I-2-2-a undergo a condensation reaction to obtain compound I-2-3;

[0513] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from N,N-dimethylformamide, tetrahydrofuran, dichloromethane, and any combination thereof. Preferably, the organic solvent is selected from N,N-dimethylformamide. The reaction is preferably carried out in the presence of a suitable condensing agent, which may be HATU, HBTU, EDCI, T3P, DCC, or DIC, etc. Preferably, the condensing agent is HATU. The reaction is preferably carried out in the presence of a suitable base, which may be N,N-diisopropylethylamine, triethylamine, N-methylmorpholine, 1,8-diazobisspirocyclic [5.4.0]undec-7-ene, 4-dimethylaminopyridine, and any combination thereof. Preferably, the base is N,N-diisopropylethylamine. The reaction is preferably carried out at a suitable temperature, preferably -10 to 80°C. The reaction is preferably carried out for a suitable time, for example, 1 to 24 hours.

[0514] (3) Compound I-2-3 undergoes a cyclization reaction to obtain compound I-2-4;

[0515] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from N,N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, toluene, and any combination thereof; preferably, the organic solvent is selected from toluene. The reaction is preferably carried out in the presence of a suitable acid, which may be methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and any combination thereof; preferably, the acid is p-toluenesulfonic acid. The reaction is preferably carried out at a suitable temperature, preferably 20-150°C. The reaction is preferably carried out for a suitable time, for example, 1-24 hours.

[0516] (4) React compound I-2-4 to obtain compound I-2-5;

[0517] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from N,N-dimethylformamide, 1,4-dioxane, tetrahydrofuran, toluene, and any combination thereof. Preferably, the organic solvent is selected from 1,4-dioxane. The reaction is preferably carried out in the presence of a suitable metal catalyst, which may be tris(dibenzylacetone)dipalladium, [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex, tetratriphenylphosphine palladium, palladium acetate, Pd(dtbpf)Cl2, and any combination thereof. Preferably, the metal catalyst is [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex. The reaction is preferably carried out in the presence of a suitable base, which may be selected from potassium acetate, potassium carbonate, potassium phosphate, cesium carbonate, and any combination thereof. Preferably, the base is selected from potassium acetate. The reaction is preferably carried out at a suitable temperature, preferably 20-150°C. The reaction is preferably carried out for a suitable time, for example, 1-24 hours.

[0518] (5) React compound I-2-5 with compound I-2-5-a to obtain compound I-2-6;

[0519] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from N,N-dimethylformamide, 1,4-dioxane, tetrahydrofuran, water, toluene, and any combination thereof. Preferably, the organic solvent is selected from a mixture of 1,4-dioxane and water. The reaction is preferably carried out in the presence of a suitable metal catalyst, which may be tris(dibenzylacetone)dipalladium, [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex, tetratriphenylphosphine palladium, or acetic acid. The reaction is preferably carried out in the presence of a suitable base, which may be selected from potassium acetate, potassium carbonate, potassium phosphate, cesium carbonate, and any combination thereof, preferably potassium carbonate; the reaction is preferably carried out at a suitable temperature, preferably 20-150°C; and the reaction is preferably carried out for a suitable time, for example, 1-24 hours.

[0520] (6) React compound I-2-6 to obtain compound I-2-7;

[0521] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from N,N-dimethylformamide, tetrahydrofuran, dichloromethane, and any combination thereof, preferably dichloromethane; the reaction is preferably carried out in the presence of a suitable acid, which may be selected from hydrochloric acid, sulfuric acid, trifluoroacetic acid, and any combination thereof, preferably trifluoroacetic acid; the reaction is preferably carried out at a suitable temperature, preferably -10 to 60°C; the reaction is preferably carried out for a suitable time, for example, 0.5 to 4 hours.

[0522] (7) Reduce compound I-2-7 to obtain compound I-2-8;

[0523] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from methanol, tetrahydrofuran, dichloromethane, and any combination thereof; preferably, the organic solvent is selected from methanol. The reaction is preferably carried out in the presence of a suitable reducing agent, which may be selected from sodium borohydride, lithium borohydride, potassium borohydride, and any combination thereof; preferably, the reducing agent is selected from sodium borohydride. The reaction is preferably carried out at a suitable temperature, preferably -10 to 60°C. The reaction is preferably carried out for a suitable time, for example, 0.5 to 4 hours.

[0524] (8) React compound I-2-8 with compound I-2-8-a to obtain compound I-2;

[0525] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from dichloromethane, 1,4-dioxane, THF, chloroform, N,N-dimethylformamide, and any combination thereof. Preferably, the organic solvent is selected from dichloromethane. The reaction is preferably carried out in the presence of a suitable base, which may be selected from N,N-diisopropylethylamine, triethylamine, N-methylmorpholine, 1,8-diazobisspirocyclo[5.4.0]undec-7-ene, and any combination thereof. Preferably, the base is selected from triethylamine. The reaction is preferably carried out at a suitable temperature, which is preferably -10 to 40°C. The reaction is preferably carried out for a suitable time, for example, 0.5 to 4 hours.

[0526] Another object of the present invention is to provide a method for preparing the compounds of the present invention. For example, the present invention provides a method for preparing compounds of formula (I-3), which includes the following steps:

[0527] Among them, R 1 R 2 R 3 R 4And m as defined above; X represents a halogen atom, including chlorine, bromine and iodine; LG represents a leaving group, such as halogen, trifluoromethanesulfonate, p-toluenesulfonate or methanesulfonate;

[0528] (1) React compound I-3-1 with I-3-1-a to obtain compound I-3-2;

[0529] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from N,N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, toluene, and any combination thereof. Preferably, the organic solvent is selected from N,N-dimethylformamide. The reaction is preferably carried out in the presence of a suitable base, which may be selected from N,N-diisopropylethylamine, cesium carbonate, potassium tert-butoxide, potassium carbonate, and any combination thereof. Preferably, the base is selected from cesium carbonate. The reaction is preferably carried out at a suitable temperature, preferably between 20 and 150°C. The reaction is preferably carried out for a suitable time, for example, 1-12 hours.

[0530] (2) React compound I-3-2 to obtain compound I-3-3;

[0531] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from N,N-dimethylformamide, 1,4-dioxane, tetrahydrofuran, toluene, and any combination thereof. Preferably, the organic solvent is selected from 1,4-dioxane. The reaction is preferably carried out in the presence of a suitable metal catalyst, which may be tris(dibenzylacetone)dipalladium, [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex, tetratriphenylphosphine palladium, palladium acetate, Pd(dtbpf)Cl2, and any combination thereof. Preferably, the metal catalyst is [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex. The reaction is preferably carried out in the presence of a suitable base, which may be selected from potassium acetate, potassium carbonate, potassium phosphate, cesium carbonate, and any combination thereof. Preferably, the base is selected from potassium acetate. The reaction is preferably carried out at a suitable temperature, preferably between 20 and 150°C. The reaction is preferably carried out for a suitable time, for example, 1-24 hours.

[0532] (3) React compound I-3-3 with compound I-2-5-a to obtain compound I-3-4;

[0533] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from N,N-dimethylformamide, 1,4-dioxane, tetrahydrofuran, water, toluene, and any combination thereof. Preferably, the organic solvent is selected from a mixture of 1,4-dioxane and water. The reaction is preferably carried out in the presence of a suitable metal catalyst, which may be tris(dibenzylacetone)dipalladium, [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex, tetratriphenylphosphine palladium, or acetic acid. The reaction is preferably carried out in the presence of a suitable base, which may be selected from potassium acetate, potassium carbonate, potassium phosphate, cesium carbonate, and any combination thereof, preferably potassium carbonate; the reaction is preferably carried out at a suitable temperature, preferably 20 to 150°C; and the reaction is preferably carried out for a suitable time, for example, 1 to 24 hours.

[0534] (4) React compound I-3-4 to obtain compound I-3-5;

[0535] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from N,N-dimethylformamide, tetrahydrofuran, dichloromethane, and any combination thereof, preferably dichloromethane; the reaction is preferably carried out in the presence of a suitable acid, which may be selected from hydrochloric acid, sulfuric acid, trifluoroacetic acid, and any combination thereof, preferably trifluoroacetic acid; the reaction is preferably carried out at a suitable temperature, preferably -10 to 60°C; and the reaction is preferably carried out for a suitable time, for example, 0.5 to 4 hours.

[0536] (5) Reduce compound I-3-5 to obtain compound I-3-6;

[0537] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from methanol, tetrahydrofuran, dichloromethane, and any combination thereof; preferably, the organic solvent is selected from methanol. The reaction is preferably carried out in the presence of a suitable reducing agent, which may be selected from sodium borohydride, lithium borohydride, potassium borohydride, and any combination thereof; preferably, the reducing agent is selected from sodium borohydride. The reaction is preferably carried out at a suitable temperature, preferably -10 to 60°C. The reaction is preferably carried out for a suitable time, for example, 0.5 to 4 hours.

[0538] (6) React compound I-3-6 with compound I-2-8-a to obtain compound I-3;

[0539] Preferably, the reaction is carried out in a suitable organic solvent, which may be selected from dichloromethane, 1,4-dioxane, THF, chloroform, N,N-dimethylformamide, and any combination thereof. Preferably, the organic solvent is selected from dichloromethane. The reaction is preferably carried out in the presence of a suitable base, which may be selected from N,N-diisopropylethylamine, triethylamine, N-methylmorpholine, 1,8-diazobisspirocyclo[5.4.0]undec-7-ene, and any combination thereof. Preferably, the base is selected from triethylamine. The reaction is preferably carried out at a suitable temperature, which is preferably from -10 to 40°C. The reaction is preferably carried out for a suitable time, for example, 0.5 to 4 hours.

[0540] Pharmaceutical compositions and therapeutic uses and methods

[0541] Another aspect of the present invention provides a pharmaceutical composition comprising a preventive or therapeutically effective amount of the compound of the present invention, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite or prodrug or pharmaceutically acceptable salt or ester thereof, and one or more pharmaceutically acceptable carriers.

[0542] In another embodiment, the pharmaceutical composition may also contain one or more other therapeutic agents.

[0543] In this invention, "pharmaceutically acceptable carrier" refers to a diluent, excipient, vehicle, or medium that is administered co-administered with a therapeutic agent and is suitable, to the extent of reasonable medical judgment, for contact with human and / or other animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications commensurate with a reasonable benefit / risk ratio.

[0544] Pharmaceutically acceptable carriers that can be used in the pharmaceutical compositions of the present invention include, but are not limited to, sterile liquids such as water and oils, including those of petroleum, animal, plant, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, etc. Water is an exemplary carrier when the pharmaceutical composition is administered intravenously. Physiological saline and aqueous solutions of glucose and glycerol can also be used as liquid carriers, particularly for injectable solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, maltose, chalk, silica gel, sodium stearate, glyceryl monostearate, talc, sodium chloride, skim milk powder, glycerol, propylene glycol, water, ethanol, etc. The compositions may also contain small amounts of wetting agents, emulsifiers, or pH buffers as needed. Oral formulations may contain standard carriers such as pharmaceutical-grade mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose, magnesium carbonate, etc. Examples of suitable pharmaceutically acceptable carriers are described in Remington's Pharmaceutical Sciences (1990).

[0545] The pharmaceutical compositions of the present invention can act systemically and / or locally. For this purpose, they can be administered via suitable routes, such as by injection, intravenous, intra-arterial, subcutaneous, intraperitoneal, intramuscular, or transdermal administration; or by oral, sublingual, nasal, transmucosal, topical, ophthalmic formulations, or inhalation administration.

[0546] For these routes of administration, the pharmaceutical compositions of the present invention can be administered in suitable dosage forms.

[0547] The dosage forms include, but are not limited to, tablets, capsules, lozenges, hard candies, powders, sprays, creams, ointments, suppositories, gels, pastes, lotions, ointments, aqueous suspensions, injectable solutions, elixirs, and syrups.

[0548] The content or amount of the compound of the present invention in the pharmaceutical composition may be from about 0.01 mg to about 1000 mg.

[0549] Another aspect of the present invention provides a pharmaceutical composition comprising a preventive or therapeutically effective amount of the compound of the present invention, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite or prodrug or pharmaceutically acceptable salt or ester thereof, and one or more pharmaceutically acceptable carriers.

[0550] Another aspect of the present invention provides the use of the compounds described herein, or stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or metabolites or prodrugs or pharmaceutically acceptable salts or esters thereof, or pharmaceutical compositions described herein, in the preparation of medicaments for the prevention and / or treatment of diseases, preferably, diseases related to NRF2 dysregulation such as tumors or cancer.

[0551] Another aspect of the present invention provides the compounds described herein, or their stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or their metabolites or prodrugs or pharmaceutically acceptable salts or esters, or the pharmaceutical compositions described herein, for the prevention and / or treatment of diseases, preferably, diseases related to NRF2 dysregulation such as tumors or cancer.

[0552] Another aspect of the present invention provides a method for preventing and / or treating a disease, the method comprising administering to an individual in need an effective amount of the compound of the present invention, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite or prodrug or pharmaceutically acceptable salt or ester thereof, or a pharmaceutical composition of the present invention.

[0553] The diseases described in this invention are NRF2 dysregulation-related diseases such as tumors or cancer.

[0554] In some embodiments, the tumor or cancer is selected from lung cancer, bladder cancer, uterine cancer, head and neck cancer, esophageal cancer, ovarian cancer, liver cancer, cervical cancer, bile duct cancer, stomach cancer, kidney cancer, and pancreatic cancer.

[0555] In some embodiments, the tumor or cancer is selected from non-small cell lung cancer, esophageal cancer, head and neck cancer, bladder cancer, endometrial cancer, and cervical cancer.

[0556] In some embodiments, the tumor or cancer is selected from squamous non-small cell lung cancer, lung adenocarcinoma, squamous cell esophageal cancer, esophageal adenocarcinoma, squamous cell head and neck cancer, squamous cell bladder cancer, and cervical squamous cell carcinoma.

[0557] In some embodiments, the tumor or cancer is selected from squamous non-small cell lung cancer and lung adenocarcinoma.

[0558] As used in this article, the term "effective amount" refers to the amount of a compound that, when administered, will alleviate one or more symptoms of the treated condition to some extent.

[0559] The dosing regimen can be adjusted to provide the optimal required response. For example, a single bolus injection can be administered, several fractions can be administered over time, or the dose can be proportionally reduced or increased as indicated by the urgency of the treatment situation. It should be noted that dosage values ​​can vary depending on the type and severity of the condition to be alleviated, and may include single or multiple doses. To further understand, for any given individual, the specific dosing regimen should be adjusted over time based on individual needs and the professional judgment of the person administering the composition or supervising its administration.

[0560] The amount of the compound of the present invention administered will depend on the individual being treated, the severity of the condition or illness, the rate of administration, the disposal of the compound, and the judgment of the prescribing physician.

[0561] Unless otherwise stated, as used herein, the term “treating” means reversing, alleviating, or suppressing the progression of one or more symptoms of the condition or illness to which the term applies.

[0562] As used herein, the term "prevention" refers to the prior administration of medication to avoid or prevent the onset of one or more symptoms of a disease or condition. Those skilled in the medical field recognize that the term "prevention" is not an absolute term. In the medical field, it should be understood as the preventive administration of medication to substantially reduce the likelihood or severity of a condition or its symptoms, which is the intended meaning of this disclosure. The Physician's Desk Reference, the standard text in the field, uses the term "prevention" hundreds of times. As used therein, the term "prevention" regarding a condition or disease refers to the avoidance of the cause, effect, symptoms, or progression of a disease or condition before it has fully manifested.

[0563] As used herein, “individual” includes both human and non-human animals. Exemplary human individuals include human individuals suffering from a disease (such as the disease described herein) (referred to as patients) or normal individuals. In this invention, “non-human animals” includes all vertebrates, such as non-mammals (e.g., birds, amphibians, reptiles) and mammals, such as non-human primates, livestock, and / or domesticated animals (e.g., sheep, dogs, cats, cows, pigs, etc.). Detailed Implementation

[0564] To make the objectives and technical solutions of this invention clearer, the embodiments of this invention are described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of this invention. Unless otherwise specified, specific conditions in the examples are performed under conventional conditions or conditions recommended by the manufacturer. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0565] The structure of the compound was determined by nuclear magnetic resonance (NMR). 1 It was determined by 1H NMR or mass spectrometry (MS). 1 The 1H NMR was performed using a JEOL Eclipse 400 NMR spectrometer. The solvents used were deuterated methanol (CD3OD), deuterated chloroform (CDCl3), or hexadeuterated dimethyl sulfoxide (DMSO-d6). The internal standard was tetramethylsilane (TMS). Chemical shifts (δ) were given in parts per million (ppm).

[0566] The instrument used for MS measurements was an Agilent (ESI) mass spectrometer, manufacturer: Agilent, model: Agilent 6120B.

[0567] Preparation method of high performance liquid chromatograph:

[0568] Instrument model: Agilent 1260; Column: Waters SunFire Prep C18 OBD (19mm×150mm×5.0μm); Column temperature: 25℃; Flow rate: 20.0mL / min; Detection wavelength: 214nm; Elution gradient: (0min: 10%A, 90%B; 16.0min: 90%A, 10%B); Mobile phase A: Acetonitrile; Mobile phase B: 0.05% formic acid aqueous solution.

[0569] The thin-layer chromatography silica gel plates (TLC) used were Merck aluminum plates (20×20cm), and the TLC separation and purification used Yantai-made GF 254 (1mm) plates.

[0570] The reaction was monitored using thin-layer chromatography (TLC) or LC-MS. The developing solvent systems used included dichloromethane and methanol, n-hexane and ethyl acetate, and petroleum ether and ethyl acetate. The volume ratio of the solvent was adjusted according to the polarity of the compound or by adding triethylamine, etc.

[0571] The microwave reaction was performed using a Biotage Initiator+ (400W, RT~300℃) microwave reactor.

[0572] Preparation method of reverse column chromatography:

[0573] Preparation method A:

[0574] Instrument model: Biotage rapid medium-pressure preparative chromatography; Column: Agela C18 reverse-flow column (Spherical; 20-35 μm; 100A); Column temperature: 25℃; Flow rate: 28.0 mL / min; Detection wavelength: 220 nm; Mobile phase A: acetonitrile; Mobile phase B: water;

[0575] Preparation method B:

[0576] Instrument model: Biotage rapid medium-pressure preparative chromatography; Column: Agela C18 reverse-flow column (Spherical; 20-35μm; 100A); Column temperature: 25℃; Flow rate: 28.0mL / min; Detection wavelength: 220nm; Mobile phase A: acetonitrile; Mobile phase B: 0.05% formic acid aqueous solution;

[0577] Preparation method C:

[0578] Instrument model: Biotage rapid medium-pressure preparative chromatography; Column: Agela C18 reverse-flow column (Spherical; 20-35 μm; 100A); Column temperature: 25℃; Flow rate: 28.0 mL / min; Detection wavelength: 220 nm; Mobile phase A: acetonitrile; Mobile phase B: 0.05% NH4HCO3 aqueous solution; Column chromatography generally uses 200-300 mesh silica gel as the support. Eluent systems include: dichloromethane and methanol systems, and petroleum ether and ethyl acetate systems. The volume ratio of the solvents is adjusted according to the polarity of the compounds, and a small amount of triethylamine can also be added for adjustment.

[0579] Unless otherwise specified in the examples, the reaction temperature is room temperature (20℃~35℃).

[0580] The reagents used in this invention were purchased from Acros Organics, Aldrich Chemical Company, and TEB Chemicals, among others.

[0581] In the conventional synthesis methods and examples, as well as intermediate synthesis examples, the meanings of the abbreviations are as follows.

[0582] Example:

[0583] Intermediate Example 1: Preparation of tert-butyl 5-((diphenoxyphosphoryl)oxy)-2,3-dihydro-4H-1,4-oxazine-4-carboxylate

[0584] 5 g (24.85 mmol) of tert-butyl 3-oxomorpholine-4-carboxylate was added to 50 mL of anhydrous THF. LiHMDS (28.6 mL, 28.6 mmol) was slowly added dropwise at -30 °C, and the mixture was stirred at this temperature for 0.5 hours. Then, diphenyl chlorophosphate (7.34 g, 27.33 mmol) was slowly added dropwise, and the mixture was slowly heated to 10 °C and reacted for 1 hour. The reaction mixture was poured into 100 mL of ice water and extracted with ethyl acetate (40 mL x 3). The organic phase was collected, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: PE / EA = 75 / 25, v / v) to give the title compound (7.5 g).

[0585] 1 H NMR (400MHz, CDCl3) δ7.39-7.27(m,4H),7.25-7.16(m,6H),6.34(d,J=4.0Hz,1H),3.97(d,J=4.0Hz,2H),3.66-3.59(d,J=4.0Hz,2H),1.44(s,9H).

[0586] Intermediate Example 2: Preparation of tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)-2,3-dihydro-4H-1,4-oxazine-4-carboxylate

[0587] 5-((diphenoxyphosphoryl)oxy)-2,3-dihydro-4H-1,4-oxazine-4-carboxylic acid tert-butyl ester (6 g, 13.84 mmol) was dissolved in 1,4-dioxane (540 mL), followed by the addition of pinacol diboronate (7.03 g, 27.69 mmol) and potassium acetate (2.72 g, 27.69 mmol). After nitrogen purging, tetrakis(triphenylphosphine)palladium (0.8 g, 0.69 mmol) was added, and the reaction mixture was heated to 90 °C and reacted for 24 hours. The reaction mixture was then added to water (1 L), extracted with ethyl acetate (200 mL x 3), and the organic phase was collected and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: PE / EA = 75 / 25, v / v) to give the title compound (3 g).

[0588] MS m / z (ESI): 256.2 [M-56+H] + .

[0589] Intermediate Example 3: Preparation of 6-bromo-4-chloro-N-methylbenzo[d]oxazol-2-carboxamide

[0590] Step 1: Preparation of methyl 6-bromo-4-chlorobenzo[d]oxazole-2-carboxylate

[0591] 2-Amino-5-bromo-3-chlorophenol (1.3 g, 5.79 mmol) was dissolved in ethylene glycol dimethyl ether (10 mL), followed by the addition of methyl 2,2,2-trimethoxyacetate (3.8 g, 23.16 mmol) and p-toluenesulfonic acid (100 mg, 0.58 mmol). The reaction mixture was heated to 100 °C and reacted for 12 hours. The reaction mixture was then added to water (30 mL), extracted with ethyl acetate (20 mL x 3), and the organic phase was collected and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: PE / EA = 70 / 30, v / v) to give the title compound of this step (1.5 g).

[0592] MS m / z(ESI): 290.0 [M+H] + .

[0593] Step 2: Preparation of 6-bromo-4-chlorobenzo[d]oxazol-2-carboxylic acid

[0594] Methyl 6-bromo-4-chlorobenzo[d]oxazol-2-carboxylate (0.2 g, 0.69 mmol) was dissolved in tetrahydrofuran (4 mL) and water (2 mL), and then lithium hydroxide monohydrate (0.15 g, 3.45 mmol) was added. The reaction solution was reacted at room temperature for 2 hours. The reaction solution was adjusted to pH 6 with dilute hydrochloric acid, extracted with ethyl acetate (20 mL x 3), and the organic phase was collected and concentrated under reduced pressure to give the crude title compound of this step (0.18 g).

[0595] MS m / z(ESI): 276.0 [M+H] + .

[0596] Step 3: Preparation of 6-bromo-4-chloro-N-methylbenzo[d]oxazol-2-carboxamide

[0597] 6-Bromo-4-chlorobenzo[d]oxazol-2-carboxylic acid (0.18 g, 0.65 mmol) was dissolved in dichloromethane (4 mL), followed by the addition of oxalyl chloride (0.16 g, 1.3 mmol) and N,N-dimethylformamide (5 mg, 0.065 mmol). The reaction mixture was reacted at room temperature for 1 hour. The solution was directly concentrated to dryness to obtain crude acyl chloride. Then, in another reaction flask, a tetrahydrofuran solution of methylamine (2 M, 3.25 mL, 6.5 mmol) was added. The prepared dichloromethane solution of acyl chloride was added dropwise under ice-water bath cooling. The reaction mixture was slowly heated to room temperature and stirred for 1 hour. The reaction mixture was added to water (20 mL), extracted with dichloromethane (20 mL x 3), and the organic phase was collected and concentrated under reduced pressure to obtain crude (0.18 g) of the title compound of this step.

[0598] MS m / z(ESI): 289.0 [M+H] + .

[0599] Intermediate Example 4: Preparation of 6-bromo-4-chloro-N-cyclopropylbenzo[d]oxazole-2-carboxamide

[0600] Using a synthetic method similar to that of intermediate Example 3, the tetrahydrofuran solution of methylamine in the third step was replaced with cyclopropylamine to obtain the crude title compound (0.16 g).

[0601] MS m / z(ESI): 315.0 [M+H] + .

[0602] Intermediate Example 5: Preparation of 7-bromo-9-chloro-5H-chromo[4,3-d]pyrimidine-2-amine

[0603] Step 1: Preparation of 8-bromo-4,6-dichloro-2H-chromene-3-carboxaldehyde

[0604] N,N-dimethylformamide (2.10 g, 28.7 mmol) was added to a solution of 8-bromo-6-chlorochrome-4-one (2.50 g, 9.56 mmol) in dichloroethane (32.5 mL), followed by phosphorus oxychloride (3.22 g, 21.0 mmol) at 0 °C. The reaction mixture was stirred at 25 °C for 12 hours. An aqueous solution of potassium carbonate was added to the reaction mixture to adjust the pH to neutral, and the mixture was extracted with ethyl acetate (20 mL x 3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude title compound (1.6 g).

[0605] 1 H NMR (400MHz, CDCl3) δ10.17 (s, 1H), 7.64 (d, J = 2.4Hz, 1H), 7.59 (d, J = 2.4Hz, 1H), 5.11 (s, 2H).

[0606] Step 2: Preparation of 7-bromo-9-chloro-5H-chromo[4,3-d]pyrimidine-2-amine

[0607] To a solution of 8-bromo-4,6-dichloro-2H-chloro-3-carboxaldehyde (7.20 g, 23.4 mmol) in ethylene glycol dimethyl ether (32 mL), guanidine hydrochloride (1.60 g, 16.7 mmol) and potassium carbonate (5.76 g, 41.8 mmol) were added. The mixture was stirred at 80 °C for 12 hours. After the reaction was complete, the reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (20 mL x 3). The combined organic layers were washed with brine, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: DCM / MeOH = 95 / 5, v / v) to give the title compound (1.2 g).

[0608] MS m / z(ESI): 312.0 [M+H] + .

[0609] Intermediate Example 6: Preparation of 5-(4-bromo-6-chloro-1H-indazol-1-yl)-N-methylpyrazine-2-amine

[0610] 4-Bromo-6-chloro-1H-indazole (300 mg, 1.30 mmol), 5-bromo-N-methylpyrazine-2-amine (243.68 mg, 1.30 mmol), and cuprous oxide (18.55 mg, 129.60 μmol) were dissolved in N,N-dimethylaniline (10 mL). The mixture was placed in a microwave reactor and heated to 120 °C with stirring for 1 hour. After the reaction was completed, the reaction solution was poured into water (50.0 mL) and extracted with ethyl acetate (20 mL x 3). The organic phase was collected, concentrated under reduced pressure, and purified by silica gel column chromatography (eluent: PE / EA = 90 / 10, v / v) to obtain the title compound (0.35 g).

[0611] MS m / z(ESI): 338.0 [M+H] + .

[0612] Intermediate Example 7: Preparation of 5-(4-bromo-6-chloro-1H-indazol-1-yl)-N-methylpyrazine-2-amine

[0613] Using a synthetic method similar to that of intermediate Example 6, 5-bromo-N-methylpyrazine-2-amine was replaced with 5-bromo-2-methoxypyridine to obtain the crude title compound (0.3 g).

[0614] MS m / z(ESI): 338.0 [M+H] + .

[0615] Intermediate Example 8: Preparation of 4-(tert-butyl)-3-(1,3-dioxoisoindoline-2-yl)morpholine-3,4-dicarboxylate

[0616] 4-(tert-Butoxycarbonyl)morpholine-3-carboxylic acid (5 g, 21.63 mmol), 2-hydroxyisoindoline-1,3-dione (3.88 g, 23.79 mmol), 4-dimethylaminopyridine (264.16 mg, 2.17 mmol), and DCC (5.35 g, 25.95 mmol) were dissolved in tetrahydrofuran (15 mL) and stirred at room temperature for 3 hours. The reaction mixture was added to water (100 mL) and extracted with EA (40.0 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed by filtration under reduced pressure. The solution was purified by column chromatography with silica gel (eluent: PE:EA = 6 / 4, v / v) to give the title compound (7.5 g).

[0617] MS m / z(ESI): 394.1 [M+NH4] + .

[0618] Intermediate Example 9: Preparation of 4-(tert-butyl)-3-(5-methoxy-1,3-dioxoisoindoline-2-yl)morpholine-3,4-dicarboxylate

[0619] Using a synthetic method similar to that of intermediate Example 8, 2-hydroxyisoindoline-1,3-dione was replaced with 2-hydroxy-5-methoxyisoindoline-1,3-dione to obtain the crude title compound (8 g).

[0620] MS m / z (ESI): 407.1 [M+H] + .

[0621] Intermediate Example 10: Preparation of tert-butyl 3-(6-chloro-1H-indazol-4-yl)morpholine-4-carboxylate

[0622] Step 1: Preparation of 6-chloro-4-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

[0623] 6-Chloro-4-iodo-1H-indazole (3 g, 10.78 mmol) was dissolved in DCM (50 mL), followed by the addition of 3,4-dihydro-2H-pyran (2.69 g, 31.67 mmol) and p-toluenesulfonic acid (272.70 mg, 1.58 mmol). The mixture was stirred at room temperature for 16 hours. The reaction solution was added to water (100 mL) and extracted with DCM (30.0 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed by filtration under reduced pressure. The solution was purified by column chromatography with silica gel (eluent: PE:EA = 10 / 1, v / v) to give the title compound (3.2 g).

[0624] MS m / z(ESI): 362.9 [M+H] + .

[0625] Step 2: Preparation of tert-butyl 3-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl)morpholine-4-carboxylic acid

[0626] 6-Chloro-4-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (2 g, 5.52 mmol), 4-(tert-butyl)3-(1,3-dioxo-1,3,3a,7a-tetrahydro-2H-isoindol-2-yl)morpholine-3,4-dicarboxylate (2.5 g, 6.62 mmol), zinc powder (3.51 g, 55.16 mmol), tetrabutylammonium iodide (2.04 g, 6.62 mmol), 5-methoxypicolinimidine hydrochloride (206.98 mg, 1.10 mmol), and nickel chloride dimethoxyethane (242.38 mg, 1.10 mmol) were placed in a reaction flask, purged with nitrogen three times, and then DMAC (36 mL) was added. Finally, a freshly prepared 10% TFA solution of DMAC (9 mL) was immediately added, and the mixture was stirred at room temperature for 2 hours. The reaction solution was added to water (100 mL) and extracted with EA (40.0 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed by filtration under reduced pressure. The solution was purified by column chromatography with silica gel (eluent: PE:EA = 10 / 3, v / v) to give the title compound (850 mg).

[0627] MS m / z(ESI): 422.2 [M+H] + .

[0628] Step 3: Preparation of 3-(6-chloro-1H-indazol-4-yl)morpholine

[0629] 1.2 g (2.85 mmol) of tert-butyl 3-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-yl)morpholine-4-carboxylic acid was dissolved in 10 mL of 1,4-dioxane, followed by the addition of 4 mL of a 4M solution of 1,4-dioxane containing hydrogen chloride. The mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was directly evaporated under reduced pressure to give the title compound (670 mg).

[0630] MS m / z(ESI): 238.1 [M+H] + .

[0631] Step 4: Preparation of tert-butyl 3-(6-chloro-1H-indazol-4-yl)morpholine-4-carboxylic acid

[0632] 3-(6-chloro-1H-indazol-4-yl)morpholine (670 mg, 2.82 mmol) was dissolved in 1,4-dioxane (10 mL), followed by the addition of 1.8 mL of 2 M sodium hydroxide aqueous solution and then di-tert-butyl dicarbonate (492.16 mg, 2.25 mmol). The mixture was stirred at room temperature for 16 hours. The reaction solution was added to water (50 mL) and extracted with EA (20.0 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed by filtration under reduced pressure, and the solution was purified by column chromatography with silica gel (eluent: PE / EA = 5 / 1, v / v) to give the title compound (500 mg).

[0633] MS m / z (ESI): 338.1 [M+H] + .

[0634] Intermediate Example 11: Preparation of tert-butyl 3-(6-chloro-4-(((trifluoromethyl)sulfonyl)oxy)quinoline-8-yl)morpholine-4-carboxylic acid

[0635] Step 1: Preparation of tert-butyl 3-(6-chloro-4-oxo-1,4-dihydroquinolin-8-yl)morpholine-4-carboxylate

[0636] 8-Bromo-6-chloroquinoline-4(1H)-one (2.6 g, 10 mmol), 4-(tert-butyl)-3-(5-methoxy-1,3-dioxoisoindolin-2-yl)morpholine-3,4-dicarboxylate (4.9 g, 12 mmol), zinc powder (6.4 g, 100 mmol), tetrabutylammonium iodide (3.7 g, 10 mmol), 5-methoxypicolinimidine hydrochloride (0.37 g, 2 mmol), and nickel chloride dimethoxyethane (0.44 g, 2 mmol) were placed in a reaction flask, nitrogen gas was purged, and then DMAC (30 mL) was added. The mixture was stirred at room temperature for 12 hours. The reaction solution was filtered and added to water (200 mL), and extracted with EA (40.0 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed by filtration under reduced pressure. The solution was purified by reverse-phase extraction (eluent: acetonitrile / water = 1 / 1, v / v) to give the title compound (650 mg).

[0637] MS m / z (ESI): 365.1 [M+H] + .

[0638] Step 2: Preparation of tert-butyl 3-(6-chloro-4-(((trifluoromethyl)sulfonyl)oxy)quinoline-8-yl)morpholine-4-carboxylic acid

[0639] 3-(6-chloro-4-oxo-1,4-dihydroquinolin-8-yl)morpholin-4-carboxylic acid tert-butyl ester (650 mg, 1.78 mmol) was dissolved in dichloromethane (8 mL), followed by the addition of triethylamine (0.36 g, 3.57 mmol). Trifluoromethanesulfonic anhydride (750 mg, 2.67 mmol) was added dropwise under ice-water bath cooling, and the mixture was stirred at room temperature for 16 hours. The reaction solution was added to water (40 mL) and extracted with DCM (20.0 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed by filtration under reduced pressure, and the solution was purified by column chromatography with silica gel (eluent: PE / EA = 4 / 1, v / v) to give the title compound (600 mg).

[0640] MS m / z(ESI): 497.1 [M+H] + .

[0641] Intermediate Example 12: Preparation of 1-benzyl 4-(tert-butyl)-2-(1,3-dioxoisoindoline-2-yl)piperazine-1,2,4-tricarboxylate

[0642] 1-((benzyloxy)carbonyl)-4-(tert-butoxycarbonyl)piperazin-2-carboxylic acid (3 g, 8.15 mmol), 4-dimethylaminopyridine (100.58 mg, 815.06 μmol), and DCC (2.04 g, 9.78 mmol) were dissolved in THF (40 mL). After stirring for 5 minutes, N-hydroxyphthalimide (1.48 g, 8.97 mmol) was added, and the mixture was stirred at 25 °C for 3 hours. After the reaction was completed, the mixture was extracted with water (100 mL) and ethyl acetate (100 mL x 3). The organic layer was collected, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography with silica gel (eluent: PE / EA = 2 / 1, v / v). The purified compound was then concentrated under reduced pressure to give the title compound (4 g).

[0643] MS m / z(ESI): 454.0 [M-56] + .

[0644] Intermediate Example 13: Preparation of tert-butyl 2-(6-chloro-1H-indazol-4-yl)-4,4-difluoropiperidine-1-carboxylate

[0645] Step 1: Preparation of 1-(tert-butyl)-2-methyl-4,4-difluoropiperidine-1,2-dicarboxylic acid ester

[0646] DAST (36.0 g, 224 mmol) was slowly added dropwise to a nitrogen-purged solution of 1-(tert-butyl)-2-methyl-4-oxopiperidin-1,2-dicarboxylic acid ester (25.0 g, 97.2 mmol) in dichloromethane (250 mL). The mixture was then stirred at -78 °C for 3 hours, and the reaction was slowly warmed to room temperature and stirred for 16 hours. The reaction was quenched by slowly adding saturated Na₂CO₃ aqueous solution (200 mL), followed by extraction with dichloromethane (200 mL x 3). The organic layer was collected, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography with silica gel (eluent: PE / EA = 1 / 10, v / v) to give the title compound (19 g).

[0647] 1 H NMR (400MHz, CDCl3) δ4.81-5.15(m,1H),3.99-4.25(m,1H),3.75(s,3H),3.10-3.41(m,1H),2.71(s,1H),1.75-2.26(m,3H),1.42-1.50(m,9H).

[0648] Step 2: Preparation of 1-(tert-Butoxycarbonyl)-4,4-difluoropiperidine-2-carboxylic acid

[0649] Under nitrogen protection, lithium hydroxide (14.7 g, 349 mmol) was added to a mixture of 1-(tert-butyl)-2-methyl-4,4-difluoropiperidine-1,2-dicarboxylic acid ester (19.5 g, 69.8 mmol) in THF (200 mL) and water (50 mL), and the reaction mixture was stirred at 25 °C for 16 h. The reaction was quenched by slowly adding 100 mL of aqueous solution, followed by extraction with ethyl acetate (100 mL) and discarding the extract. The aqueous phase was adjusted to pH 4-5 with dilute hydrochloric acid and then extracted with ethyl acetate (100 mL x 3). The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude title compound (18 g).

[0650] MS m / z(ESI): 266.2 [M+H] + .

[0651] Step 3: Preparation of 1-(tert-butyl)2-(1,3-dioxoisoindololin-2-yl)4,4-difluoropiperidine-1,2-dicarboxylic acid ester

[0652] Under 0°C ice-water bath cooling, 1-(tert-butyloxycarbonyl)-4,4-difluoropiperidine-2-carboxylic acid (6.92 g, 26.1 mmol), 2-hydroxyisoindoline-1,3-dione (4.68 g, 28.7 mmol), DMAP (319 mg, 2.61 mmol), and DCM (70 mL) were added sequentially to the reaction flask, followed by the addition of EDCI (6 g, 31.31 mmol) in portions and stirring at room temperature for 2 hours. Water (100 mL) was slowly added to the reaction mixture, followed by extraction with ethyl acetate (100 mL x 3). The organic layer was collected, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography with silica gel (eluent: PE / EA = 1 / 10, v / v) to give the title compound (2 g).

[0653] MS m / z (ESI): 310.9 [M+H] + .

[0654] Step 4: Preparation of tert-butyl 2-(6-chloro-1H-indazol-4-yl)-4,4-difluoropiperidine-1-carboxylate

[0655] Under 0°C ice-water bath cooling, 6-chloro-4-iodo-1H-indazole (500 mg, 1.80 mmol), 1-(tert-butyl)-2-(1,3-dioxoisoindoline-2-yl)4,4-difluoropiperidine-1,2-dicarboxylic acid ester (884 mg, 2.15 mmol), 5-methoxypyridine-2-formamidinium hydrochloride (67.4 mg, 359 μmol), tetrabutylammonium iodide (663 mg, 1.80 mmol), zinc powder (3.65 g, 55.8 mmol), nickel chloride dimethoxyethane (78.9 mg, 359 μmol), and DMAC (5 mL) were added sequentially to the nitrogen-purged reaction flask. The mixed solution was then purged with nitrogen three times again. TFA (102 mg, 898 μmol) was slowly added dropwise at 0°C. The reaction was slowly warmed to room temperature and stirred for 12 hs. The reaction solution was diluted with ethyl acetate (100 mL), filtered through a diatomaceous earth filter, and the filtrate was washed three times with brine (20 mL x 3). The organic layer was collected, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography with silica gel (eluent: PE / EA = 1 / 6, v / v) to give the title compound (100 mg).

[0656] MS m / z(ESI): 372.1 [M+H] + .

[0657] Intermediate Example 14: Preparation of 1-(tert-butyl)-2-methyl-4-(difluoromethylene)piperidine-1,2-dicarboxylic acid ester

[0658] Under a dry ice-acetonitrile bath cooling at -40°C, 1-(tert-butyl)-2-methyl-4-oxopiperidin-1,2-dicarboxylic acid ester (5 g, 19.4 mmol), 2-((difluoromethyl)sulfonyl)pyridine (4.1 g, 21.4 mmol), and DMF (40 mL) were added to a nitrogen-purged reaction flask. A solution of potassium tert-butoxide (3.27 g, 29.15 mmol) in DMF (10 mL) was then slowly added dropwise. The mixture was stirred at -40°C for 30 minutes, and the reaction was slowly warmed to room temperature with stirring for 2 hours. A saturated citric acid aqueous solution was slowly added dropwise to adjust the pH to neutral. The mixture was extracted three times with ethyl acetate (100 mL x 3). The organic layer was collected, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography with silica gel (eluent: PE / EA = 1 / 12, v / v) to give the title compound (1.6 g).

[0659] MS m / z (ESI): 178.1 [M+H] + .

[0660] 1 H NMR (400MHz, CDCl3) δ4.73-5.07(m,1H),3.92-4.16(m,1H),3.73(s,3H),2.85-3 .08(m,2H),2.29-2.44(m,1H),2.23(s,1H),1.99(m,J=2.8Hz,1H),1.47(s,9H).

[0661] Intermediate Example 15: Preparation of 1-(tert-butyl)-2-methyl-4-(difluoromethylene)piperidine-1,2-dicarboxylic acid ester

[0662] Using a synthetic method similar to that of intermediate Example 13, the starting material 1-(tert-butyl)-2-methyl-4,4-difluoropiperidine-1,2-dicarboxylic acid ester in step 2 was replaced with 1-(tert-butyl)-2-methyl-4-(difluoromethylene)piperidine-1,2-dicarboxylic acid ester to obtain the title compound (150 mg).

[0663] MS m / z (ESI): 384.1 [M+H] + .

[0664] Example 1: Preparation of 1-(3-(4-chloro-2-(1H-pyrazol-4-yl)benzo[d]oxazol-6-yl)morpholino)prop-2-en-1-one (compound 1)

[0665] Step 1: Preparation of 2-amino-5-bromo-3-chlorophenol

[0666] 2-Amino-3-chlorophenol (1.5 g, 10.45 mmol) was dissolved in DCM (40 mL), and bromine (2.51 g, 15.69 mmol) was added dropwise at 0 °C. After slowly restoring to room temperature, the reaction was carried out for 12 hours. The reaction solution was filtered, and the solid was dissolved in saturated NaHCO3 aqueous solution (150 mL) and extracted with DCM (30 mL x 3). The organic phase was collected, concentrated under reduced pressure, and the residue was purified by reversed-phase column chromatography (Preparation Method A) to obtain the title compound of this step (0.96 g).

[0667] MS m / z(ESI): 221.9 [M+H] + .

[0668] Step 2: Preparation of 1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylic acid-2-amino-5-bromo-3-chlorophenyl ester

[0669] 1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylic acid (208 mg, 0.90 mmol) was dissolved in DMF (6 mL), and HATU (444 mg, 1.17 mmol) and DIPEA (232 mg, 1.8 mmol) were added. The mixture was stirred for 20 minutes, and then 2-amino-5-bromo-3-chlorophenol (200 mg, 0.90 mmol) was added. The reaction mixture was reacted at room temperature for 12 hours. The reaction mixture was added to water (100 mL), extracted with ethyl acetate (20 mL x 3), and the organic phase was collected and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: PE / EA = 50 / 50, v / v) to give the title compound of this step (0.3 g).

[0670] MS m / z(ESI): 436.0 [M+H] + .

[0671] 1 H NMR (400MHz, DMSO-d6) δ8.65(d,J=0.8Hz,1H),8.05(d,J=0.8Hz,1H),7.38(d,J=2.4Hz,1H),7.3 3-7.28(m,2H),7.25(d,J=2.4Hz,1H),6.97-6.87(m,2H),5.47(s,2H),5.33(s,2H),3.74(s,3H).

[0672] Step 3: Preparation of 6-bromo-4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazole

[0673] 1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylic acid-2-amino-5-bromo-3-chlorophenyl ester (0.3 g, 0.68 mmol) was dissolved in toluene (10 mL), and p-toluenesulfonic acid (60 mg, 0.34 mmol) was added. The mixture was heated to 100 °C and reacted for 4 hours. The reaction solution was diluted with EA (60 mL), washed successively with saturated NaHCO3 aqueous solution (20 mL) and brine (20 mL), and the organic phase was dried and concentrated under reduced pressure to obtain the crude title compound (0.3 g).

[0674] MS m / z(ESI): 418.0 [M+H] + .

[0675] Step 4: Preparation of 4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborhexacyclopentan-2-yl)benzo[d]oxazole

[0676] 6-Bromo-4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazole (0.22 g, 0.53 mmol) was dissolved in 1,4-dioxane (10 mL), followed by the addition of pinacol diboronate (267 mg, 1.05 mmol) and potassium acetate (155 mg, 1.58 mmol). After nitrogen purging, [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane dichloride complex (43 mg, 0.05 mmol) was added. The reaction mixture was heated to 100 °C and reacted for 12 hours. The reaction mixture was then added to water (60 mL), extracted with ethyl acetate (20 mL x 3), and the organic phase was collected and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: PE / EA = 80 / 20, v / v) to give the title compound of this step (0.2 g).

[0677] MS m / z (ESI): 466.2 [M+H] + .

[0678] Step 5: Preparation of tert-butyl 5-(4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazol-6-yl)-2,3-dihydro-4H-1,4-oxazine-4-carboxylate

[0679] 4-Chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborhexacyclopentan-2-yl)benzo[d]oxazole (0.2 g, 0.43 mmol) was dissolved in a mixed solvent of 1,4-dioxane (10 mL) and water (2 mL). 5-((diphenoxyphosphoryl)oxy)-2,3-dihydro-4H-1,4-oxazine-4-carboxylic acid tert-butyl ester (205 mg, 0.47 mmol) and potassium carbonate (118 mg, 0.86 mmol) were added. After nitrogen purging, [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane dichloride complex (35 mg, 0.042 mmol) was added. The reaction solution was heated to 100 °C and reacted for 12 hours. The reaction solution was added to water (60 mL), extracted with ethyl acetate (20 mL x 3), the organic phase was collected, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: PE / EA = 65 / 35, v / v) to obtain the title compound of this step (0.2 g).

[0680] MS m / z(ESI): 523.2 [M+H] + .

[0681] Step 6: Preparation of 4-chloro-6-(5,6-dihydro-2H-1,4-oxazin-3-yl)-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazole

[0682] 180 mg (0.344 mmol) of tert-butyl 5-(4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazol-6-yl)-2,3-dihydro-4H-1,4-oxazine-4-carboxylic acid was dissolved in 2 mL of DCM. Trifluoroacetic acid (1 mL) was added dropwise at 0 °C, and the mixture was slowly brought to room temperature with stirring for 1 hour. The reaction solution was concentrated under reduced pressure to obtain the crude title compound (0.18 g).

[0683] MS m / z(ESI): 423.1 [M+H] + .

[0684] Step 7: Preparation of 4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-6-(morpholin-3-yl)benzo[d]oxazole

[0685] 4-Chloro-6-(5,6-dihydro-2H-1,4-oxazin-3-yl)-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazole (180 mg, 0.425 mmol) was dissolved in methanol (6 mL), and sodium borohydride (80 mg, 2.13 mmol) was added at 0 °C. The mixture was slowly brought to room temperature and stirred for 1 hour. The reaction solution was added to an aqueous solution of ammonium chloride (60 mL), extracted with EA (20 mL x 3), and the organic phase was collected and concentrated under reduced pressure to give the title compound of this step (0.17 g).

[0686] MS m / z (ESI): 425.1 [M+H] + .

[0687] Step 8: Preparation of 4-chloro-6-(morpholin-3-yl)-2-(1H-pyrazol-4-yl)benzo[d]oxazole

[0688] 4-Chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-6-(morpholin-3-yl)benzo[d]oxazole (170 mg, 0.4 mmol) was dissolved in dichloroethane (2 mL), and trifluoroacetic acid (1 mL) was added at room temperature. The mixture was then heated to 70 °C and reacted for 3 hours. The reaction solution was concentrated, and the residue was adjusted to pH 9 with NaHCO3 aqueous solution. The residue was extracted with ethyl acetate (20 mL x 3), and the organic phase was collected and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: DCM / MeOH = 90 / 10, v / v) to give the title compound of this step (70 mg).

[0689] MS m / z (ESI): 305.1 [M+H] + .

[0690] Step 9: Preparation of 1-(3-(4-chloro-2-(1H-pyrazol-4-yl)benzo[d]oxazol-6-yl)morpholino)prop-2-en-1-one

[0691] 4-Chloro-6-(morpholin-3-yl)-2-(1H-pyrazol-4-yl)benzo[d]oxazole (70 mg, 0.23 mmol) was dissolved in dichloromethane (3 mL), and triethylamine (70 mg, 0.69 mmol) was added. Acryloyl chloride (13 mg, 0.14 mmol) was slowly added at 0 °C and stirred for 1 hour. The reaction solution was added to water (40 mL), extracted with DCM (20 mL x 3), the organic phase was collected, concentrated under reduced pressure, and the residue was purified by preparative high performance liquid chromatography to obtain the title compound (10 mg).

[0692] MS m / z (ESI): 359.1 [M+H] + .

[0693] 1 H NMR (400MHz, DMSO-d6) δ13.67(s,1H),8.68(s,1H),8.26-8.18(m,1H),7.67(s,1H),7.43(s,1H),6.88(dd,J=16.4,10.4Hz,1H),6 .24(dd,J=16.4,2.4Hz,1H),5.82-5.73(m,1H),4.47(d,J=12.4Hz,1H),3.97-3.75(m,3H),3.57-3.47(m,1H),3.25-3.32(m,2H).

[0694] Example 2: Preparation of 1-(3-(1-(6-aminopyrimidin-4-yl)-6-chloro-1H-indazol-4-yl)morpholino)prop-2-en-1-one (compound 15)

[0695] Step 1: Preparation of 6-(4-bromo-6-chloro-1H-indazol-1-yl)pyrimidin-4-amine

[0696] 4-Bromo-6-chloro-1H-indazole (500 mg, 2.16 mmol), tert-butyl tert-butyl 6-chloropyrimidin-4-yl carbamate (712.34 mg, 2.16 mmol), and cesium carbonate (1.41 g, 4.32 mmol) were added to DMF (10 mL) and reacted in a microwave-assisted reaction at 120 °C for 2 hours. The reaction mixture was poured into water (50 mL), extracted with ethyl acetate (30 mL x 3), and the organic phase was collected and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: PE / EA = 50 / 50, v / v) to give the title compound of this step (200 mg).

[0697] MS m / z(ESI): 324.0 [M+H] + .

[0698] Step 2: Preparation of 6-(6-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborhexacyclopentan-2-yl)-1H-indazol-1-yl)pyrimidin-4-amine

[0699] 6-(4-bromo-6-chloro-1H-indazol-1-yl)pyrimidin-4-amine (120 mg, 369.73 μmol), pinacol diboronate (93.89 mg, 369.73 μmol), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (27.05 mg, 36.97 μmol), and AcOK (108.86 mg, 1.11 mmol) were added to 1,4-dioxane (5 mL), and the mixture was heated to 100 °C and stirred for 5 hours under nitrogen protection. The reaction mixture was poured into water (50 mL), extracted with ethyl acetate (30 mL x 3), and the organic phase was collected and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: PE / EA = 60 / 40, v / v) to give the title compound of this step (70 mg).

[0700] MS m / z(ESI): 372.1 [M+H] + .

[0701] Step 3: Preparation of tert-butyl 5-(1-(6-aminopyrimidin-4-yl)-6-chloro-1H-indazol-4-yl)-2,3-dihydro-4H-1,4-oxazine-4-carboxylate

[0702] 6-(6-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboranecyclopentan-2-yl)-1H-indazol-1-yl)pyrimidin-4-amine (70 mg, 188.36 μmol), 5-((diphenoxyphospho)oxy)-2,3-dihydro-4H-1,4-oxazine-4-carboxylic acid tert-butyl ester (81.63 mg, 188.36 μmol), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride dichloromethane complex (13.78 mg, 18.84 μmol), and potassium carbonate (52.06 mg, 376.72 μmol) were added to a mixed solvent of 1,4-dioxane (5 mL) and water (1 mL), and the mixture was heated to 80 °C and stirred for 2.5 hours under nitrogen protection. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: PE / EA = 60 / 40, volume ratio) to obtain the title compound of this step (41 mg).

[0703] MS m / z (ESI): 429.1 [M+H] + .

[0704] Step 4: Preparation of 6-(6-chloro-4-(3,4-dihydro-2H-1,4-oxazin-5-yl)-1H-indazol-1-yl)pyrimidin-4-amine

[0705] 40 mg (93.27 μmol) of tert-butyl 5-(1-(6-aminopyrimidin-4-yl)-6-chloro-1H-indazol-4-yl)-2,3-dihydro-4H-1,4-oxazine-4-carboxylic acid was dissolved in DCM (5 mL), and trifluoroacetic acid (1 mL) was added. The mixture was stirred at room temperature for 12 hours. Saturated NaHCO3 aqueous solution was added to the reaction solution until no gas was produced. The mixture was extracted with ethyl acetate (30 mL x 3), and the organic phase was collected and concentrated under reduced pressure to give the title compound of this step (35 mg).

[0706] MS m / z(ESI): 329.1 [M+H] + .

[0707] Step 5: Preparation of 6-(6-chloro-4-(morpholin-3-yl)-1H-indazol-1-yl)pyrimidin-4-amine

[0708] 6-(6-chloro-4-(3,4-dihydro-2H-1,4-oxazin-5-yl)-1H-indazol-1-yl)pyrimidin-4-amine (35 mg, 106.46 μmol) was dissolved in methanol (6 mL), and sodium borohydride (8.06 mg, 212.92 μmol) was added. The mixture was stirred at room temperature for 12 hours. A saturated aqueous solution of NaHCO3 (50 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (30 mL x 3). The organic phase was collected, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: MeOH / DCM = 90 / 10, v / v) to give the title compound of this step (10 mg).

[0709] MS m / z(ESI): 331.2 [M+H] + .

[0710] Step 6: Preparation of 1-(3-(1-(6-aminopyrimidin-4-yl)-6-chloro-1H-indazol-4-yl)morpholino)prop-2-en-1-one

[0711] 6-(6-chloro-4-(morpholin-3-yl)-1H-indazol-1-yl)pyrimidin-4-amine (10 mg, 30.23 μmol) and triethylamine (4.59 mg, 45.35 μmol) were dissolved in DCM (5 mL), and acryloyl chloride (1.64 mg, 18.14 μmol) was added. The mixture was stirred at room temperature for 1 hour. The reaction solution was poured into water, extracted with ethyl acetate (10 mL x 3), and the organic phase was collected and concentrated under reduced pressure. The residue was purified by preparative high-performance liquid chromatography to give the title compound (2 mg).

[0712] MS m / z(ESI): 331.2 [M+H] + .

[0713] 1 H NMR (400MHz, DMSO-d6) δ8.82(s,1H),8.49(s,1H),8.44(d,J=1.2Hz,1H),7.55(s,1 H),7.17(s,2H),6.94(d,J=0.8Hz,1H),6.80-6.86(m,1H),6.23(dd,J=16.8,2.4Hz ,1H),5.98(s,1H),5.76(d,J=10.4Hz,1H),4.42(d,J=12.0Hz,1H),3.97(dd,J=11. 6,3.2Hz,1H),3.88-3.91(m,2H),3.57(td,J=11.7,2.4Hz,1H),3.22-3.28(m,1H).

[0714] Example 3: Preparation of 6-(4-Acryloylmorpholin-3-yl)-4-chloro-N-methylbenzo[d]oxazol-2-carboxamide (compound 5)

[0715] Step 1: Preparation of tert-butyl 5-(4-chloro-2-(methylcarbamoyl)benzo[d]oxazol-6-yl)-2,3-dihydro-4H-1,4-oxazine-4-carboxylate

[0716] 6-Bromo-4-chloro-N-methylbenzo[d]oxazol-2-carboxamide (0.18 g, 0.62 mmol) was dissolved in a mixed solvent of 1,4-dioxane (10 mL) and water (2 mL). 5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)-2,3-dihydro-4H-1,4-oxazine-4-carboxylic acid tert-butyl ester (290 mg, 0.93 mmol) and potassium carbonate (172 mg, 1.24 mmol) were added. After nitrogen purging, [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane dichloride complex (50 mg, 0.062 mmol) was added. The reaction solution was heated to 100 °C and reacted for 12 hours. The reaction solution was added to water (30 mL), extracted with ethyl acetate (20 mL x 3), the organic phase was collected, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: PE / EA = 65 / 35, v / v) to obtain the title compound of this step (90 mg).

[0717] MS m / z(ESI): 394.1 [M+H] + .

[0718] Step 2: Preparation of 4-chloro-6-(5,6-dihydro-2H-1,4-oxazin-3-yl)-N-methylbenzo[d]oxazol-2-carboxamide

[0719] 90 mg (0.23 mmol) of tert-butyl 5-(4-chloro-2-(methylcarbamoyl)benzo[d]oxazol-6-yl)-2,3-dihydro-4H-1,4-oxazine-4-carboxylate was dissolved in dichloromethane (2 mL), and trifluoroacetic acid (1 mL) was added dropwise at 0 °C. The mixture was slowly brought to room temperature and stirred for 1 hour. Saturated sodium bicarbonate solution was added to the reaction solution until no gas was produced. The mixture was extracted with dichloromethane (20 mL x 3), and the organic phase was collected and concentrated under reduced pressure to obtain the title compound (90 mg) of this step.

[0720] MS m / z(ESI): 294.1 [M+H] + .

[0721] Step 3: Preparation of 4-chloro-N-methyl-6-(morpholin-3-yl)benzo[d]oxazol-2-carboxamide

[0722] 4-Chloro-6-(5,6-dihydro-2H-1,4-oxazin-3-yl)-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazole (90 mg, 0.31 mmol) was dissolved in methanol (4 mL), and sodium borohydride (58 mg, 1.53 mmol) was added at 0 °C. The mixture was slowly brought to room temperature and stirred for 1 hour. The reaction solution was added to an aqueous solution of ammonium chloride (30 mL), extracted with EA (20 mL x 3), and the organic phase was collected and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: DCM / MeOH = 95 / 5, v / v) to give the title compound of this step (20 mg).

[0723] MS m / z(ESI): 296.1 [M+H] + .

[0724] Step 4: Preparation of 6-(4-Acryloylmorpholin-3-yl)-4-chloro-N-methylbenzo[d]oxazol-2-carboxamide

[0725] 4-Chloro-N-methyl-6-(morpholin-3-yl)benzo[d]oxazol-2-carboxamide (20 mg, 0.067 mmol) was dissolved in dichloromethane (3 mL), and triethylamine (34 mg, 0.34 mmol) was added. Acryloyl chloride (5 mg, 0.054 mmol) was slowly added at 0 °C and stirred for 1 hour. The reaction solution was added to water (20 mL), extracted with DCM (20 mL x 3), the organic phase was collected, concentrated under reduced pressure, and the residue was purified by preparative high performance liquid chromatography to obtain the title compound (7 mg).

[0726] MS m / z (ESI): 350.1 [M+H] + .

[0727] 1 H NMR (400MHz, DMSO-d6) δ9.32-9.25(m,1H),7.82(s,1H),7.55(s,1H),6.87(dd,J=16.0,10.4Hz,1H),6.23(dd,J=16.4,2.4Hz,1H),5. 70-5.50(m,1H),5.64(s,1H),4.48(d,J=12.4Hz,1H),3.95-3.77(m,3H),3.58-3.48(m,1H),3.30-3.25(m,1H),2.83(d,J=4.8Hz,3H).

[0728] Example 4: Preparation of 6-(4-Acryloylmorpholin-3-yl)-4-chloro-N-cyclopropylbenzo[d]oxazol-2-carboxamide (Compound 7)

[0729] Using a synthetic method similar to that in Example 3, the first step of 6-bromo-4-chloro-N-methylbenzo[d]oxazole-2-carboxamide was replaced with 6-bromo-4-chloro-N-cyclopropylbenzo[d]oxazole-2-carboxamide to obtain the title compound (7 mg).

[0730] MS m / z(ESI): 376.1 [M+H] + .

[0731] 1 H NMR(400MHz,DMSO-d6)δ9.42-9.37(m,1H),7.81(s,1H),7.55(s,1H),6.87(dd ,J=16.4,10.4Hz,1H),6.23(dd,J=16.4,2.4Hz,1H),5.77(dd,J=10.4,2.4Hz,1 H),5.67-5.41(m,1H),4.47(d,J=12.4Hz,1H),3.97-3.73(m,3H),3.53(td,J= 12.0, 2.8Hz, 1H), 3.30-3.25 (m, 1H), 2.93 (d, J = 5.2Hz, 1H), 0.77-0.68 (m, 4H).

[0732] Example 5: Preparation of 1-(3-(6-chloro-1-(5-methoxypyridin-2-yl)-1H-indazol-4-yl)morpholino)prop-2-en-1-one (compound 19)

[0733] Using a synthetic method similar to that in Example 3, the first step of 6-bromo-4-chloro-N-methylbenzo[d]oxazole-2-carboxamide was replaced with 4-bromo-6-chloro-1-(5-methoxypyridin-2-yl)-1H-indazole to obtain the title compound (8 mg).

[0734] MS m / z(ESI): 399.1 [M+H] + .

[0735] 1 H NMR (400MHz, DMSO-d6) δ8.67 (s, 1H), 8.43 (s, 1H), 8.33 (d, J = 2.8Hz, 1H), 7. 93(d,J=9.2Hz,1H),7.67(dd,J=9.2,3.2Hz,1H),7.51(s,1H),6.80-6.80(m, 1H),6.25(dd,J=16.8,2.4Hz,1H),5.99(s,1H),5.76(d,J=10.0Hz,1H),4.45 (d,J=12.4Hz,1H),4.02-3.86(m,6H),3.61-3.55(m,1H),3.31-3.24(m,1H).

[0736] Example 6: Preparation of 1-(3-(6-chloro-1-(5-(methylamino)pyrazin-2-yl)-1H-indazol-4-yl)morpholino)prop-2-en-1-one (compound 25)

[0737] Using a synthetic method similar to that in Example 3, the first step of 6-bromo-4-chloro-N-methylbenzo[d]oxazol-2-carboxamide was replaced with 5-(4-bromo-6-chloro-1H-indazol-1-yl)-N-methylpyrazine-2-amine to obtain the title compound (4 mg).

[0738] MS m / z(ESI): 399.1 [M+H] + .

[0739] 1H NMR (400MHz, DMSO-d6) δ8.67 (s, 1H), 8.43 (s, 1H), 8.33 (d, J = 2.8Hz, 1H), 7. 93(d,J=9.2Hz,1H),7.67(dd,J=9.2,3.2Hz,1H),7.51(s,1H),6.80-6.80(m, 1H),6.25(dd,J=16.8,2.4Hz,1H),5.99(s,1H),5.76(d,J=10.0Hz,1H),4.45 (d,J=12.4Hz,1H),4.02-3.86(m,6H),3.61-3.55(m,1H),3.31-3.24(m,1H).

[0740] Example 7: Preparation of 1-(3-(2-amino-9-chloro-5H-chromen[4,3-d]pyrimidin-7-yl)morpholino)prop-2-en-1-one (compound 49)

[0741] Using a synthetic method similar to that in Example 3, the first step of 6-bromo-4-chloro-N-methylbenzo[d]oxazol-2-carboxamide was replaced with 7-bromo-9-chloro-5H-chromeno[4,3-d]pyrimidine-2-amine to obtain the title compound (2 mg).

[0742] MS m / z (ESI): 375.1 [M+H] + .

[0743] 1 H NMR (400MHz, DMSO-d6) δ8.21(s,1H),7.90(d,J=2.8Hz,1H),7.63-7.18(m,1H),6.82(s,3H),6.16(dd,J=16.8,2.4Hz,1H),5.73(d, J=10.4Hz,1H),5.59-5.32(m,1H),5.25-5.04(m,2H),4.43-3.84(m,3H),3.89-3.73(m,1H),3.55-3.43(m,1H),3.27-2.84(m,1H).

[0744] Example 8: Preparation of 1-(3-(1-(5-aminopyrazin-2-yl)-6-chloro-1H-indazol-4-yl)morpholino)prop-2-en-1-one (compound 105)

[0745] Step 1: Preparation of tert-butyl 3-(1-(5-((tert-butyloxycarbonyl)amino)pyrazin-2-yl)-6-chloro-1H-indazol-4-yl)morpholine-4-carboxylic acid

[0746] 3-(6-chloro-1H-indazol-4-yl)morpholino-4-carboxylic acid tert-butyl ester (120 mg, 355.24 μmol), (5-bromopyrazin-2-yl)carbamate tert-butyl ester (116.85 mg, 426.28 μmol), potassium phosphate (150.81 mg, 710.47 μmol), cuprous iodide (6.77 mg, 35.52 μmol), and trans-N,N-dimethylcyclohexanediamine (5.05 mg, 35.52 mmol) were dissolved in DMSO (5 mL), then purged with nitrogen, and stirred at 120 °C for 16 hours. After the reaction was complete, the mixture was extracted with EA (20 mL x 3), the organic phases were combined and dried over anhydrous sodium sulfate, filtered to remove the solvent under reduced pressure, and purified by column chromatography with silica gel (eluent: PE / EA = 10 / 3, v / v) to give the title compound (65 mg).

[0747] MS m / z(ESI): 531.1 [M+H] + .

[0748] Step 2: Preparation of 5-(6-chloro-4-(morpholin-3-yl)-1H-indazol-1-yl)pyrazin-2-amine

[0749] 65 mg (150.85 μmol) of tert-butyl morpholino-4-carboxylate was dissolved in 1 mL of dichloromethane. Trifluoroacetic acid (1 mL) was added dropwise at 0 °C, and the mixture was slowly brought to room temperature with stirring for 1 hour. Saturated sodium bicarbonate solution was added to the reaction mixture until no gas was produced. The mixture was extracted with 20 mL x 3 of dichloromethane, and the organic phase was collected and concentrated under reduced pressure to give the title compound (35 mg) of this step.

[0750] MS m / z(ESI): 331.0 [M+H] + .

[0751] Step 3: Preparation of 1-(3-(1-(5-aminopyrazin-2-yl)-6-chloro-1H-indazol-4-yl)morpholino)prop-2-en-1-one

[0752] 5-(6-chloro-4-(morpholin-3-yl)-1H-indazol-1-yl)pyrazin-2-amine (27 mg, 81.63 μmol) was dissolved in DMF (3 mL), and triethylamine (9.09 mg, 89.79 mmol) was added. Acryloyl chloride (7.39 mg, 81.63 mmol) was slowly added at 0 °C and stirred at room temperature for 1 hour. The reaction solution was added to water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phase was collected, concentrated under reduced pressure, and the residue was purified by preparative high performance liquid chromatography to obtain the title compound (12 mg).

[0753] MS m / z (ESI): 385.1 [M+H] + .

[0754] 1 H NMR (400MHz, DMSO-d6) δ8.50(d,J=1.6Hz,1H),8.39(s,1H),8.33(s,1H),7.86(d,J=1.6Hz,1H),7.47(s,1H),6.90-6.76(m,1H),6.64(s,2H ), 6.28-6.20(m,1H),5.98(s,1H),5.76(d,J=10.4Hz,1H),4.44(d,J=12.4Hz,1H),4.01-3.87(m,3H),3.64-3.46(m,1H),3.30-3.19(m,1H).

[0755] Example 9: Preparation of 1-(3-(1-(2-aminopyrimidin-5-yl)-6-chloro-1H-indazol-4-yl)morpholino)prop-2-en-1-one (compound 107)

[0756] Using a synthetic method similar to that in Example 8, the first-step starting material (5-bromopyrazin-2-yl) tert-butyl carbamate was replaced with (5-iodopyrimidin-2-yl) tert-butyl carbamate, the solvent DMSO was replaced with acetonitrile, and the temperature was changed to 80°C to obtain the title compound (2 mg).

[0757] MS m / z (ESI): 385.1 [M+H] + .

[0758] 1H NMR(400MHz,DMSO-d6)δ8.53(s,2H),8.38(s,1H),7.67(s,1H),7.44(s,1H),7.11(s,2H),6.86-6.78(m,1H),6.28-6.23(m, 1H), 5.98 (s, 1H), 5.77 (d, J = 10.4Hz, 1H), 4.44 (d, J = 12.4Hz, 1H), 4.01-3.85 (m, 3H), 3.61-3.53 (m, 1H), 3.27-3.19 (m, 1H).

[0759] Example 10: Preparation of 1-(3-(6-chloro-1-(1H-pyrazol-3-yl)-1H-indazol-4-yl)morpholino)prop-2-en-1-one (compound 17)

[0760] Using a synthetic method similar to that in Example 8, the first-step starting material (5-bromopyrazin-2-yl) tert-butyl carbamate was replaced with 3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole to obtain the title compound (3 mg).

[0761] MS m / z (ESI): 358.1 [M+H] + .

[0762] 1 H NMR(400MHz,DMSO-d6)δ12.99(s,1H),8.36(s,1H),8.30(s,1H),7.91(s,1H),7.47(s,1H),6.86-6.78(m,1H),6.60-6.54(m,1H),6.2 7-6.18(m,1H),5.97(s,1H),5.76(d,J=10.4Hz,1H),4.45(d,J=12.4Hz,1H),4.00-3.85(m,3H),3.60-3.51(m,1H),3.28-3.20(m,1H).

[0763] Example 11: Preparation of 6-(4-(4-acryloylmorpholin-3-yl)-6-chloro-1H-indazol-1-yl)pyrimidin-4(3H)-one (compound 109)

[0764] Using a synthetic method similar to that in Example 8, the first-step starting material (5-bromopyrazin-2-yl)carbamate tert-butyl ester was replaced with 4-chloro-6-((4-methoxybenzyl)oxy)pyrimidine to obtain the title compound (2 mg).

[0765] MS m / z (ESI): 386.1 [M+H]+ .

[0766] 1 H NMR(400MHz,DMSO-d6)δ12.82(s,1H),8.71(s,1H),8.54(s,1H),8.46(s,1H),7.56(s,1H),6.87-6.76(m,1H),6.65(s,1H),6.31-6 .17(m,1H),5.96(s,1H),5.76(d,J=10.4Hz,1H),4.41(d,J=12.4Hz,1H),4.04-3.85(m,3H),3.63-3.50(m,1H),3.29-3.22(m,1H).

[0767] Example 12: Preparation of 1-(3-(4-(4-aminopyrimidin-2-yl)-6-chloroquinoline-8-yl)morpholine)prop-2-en-1-one (compound 31)

[0768] Step 1: Preparation of (8-(4-(tert-Butoxycarbonyl)morpholin-3-yl)-6-chloroquinolin-4-yl)boronic acid

[0769] 3-(6-chloro-4-(((trifluoromethyl)sulfonyl)oxy)quinoline-8-yl)morpholine-4-carboxylic acid tert-butyl ester (0.15 g, 0.30 mmol) was dissolved in 1,4-dioxane (10 mL), followed by the addition of pinacol diboronate (0.15 g, 0.60 mmol) and potassium acetate (90 mg, 0.9 mmol). After nitrogen purging, palladium dichloride bis(triphenylphosphine) (21 mg, 0.03 mmol) was added, and the reaction mixture was heated to 50 °C and reacted for 6 hours. The reaction mixture was filtered through diatomaceous earth, diluted with water, and extracted with ethyl acetate (20 mL x 3). The organic phase was collected, concentrated under reduced pressure, and the crude product of the title compound (0.2 g) was obtained.

[0770] MS m / z(ESI): 393.1 [M+H] + .

[0771] Step 2: Preparation of tert-butyl 3-(4-(4-aminopyrimidin-2-yl)-6-chloroquinoline-8-yl)morpholine-4-carboxylate

[0772] (8-(4-(tert-Butoxycarbonyl)morpholin-3-yl)-6-chloroquinoline-4-yl)boronic acid (0.2 g, 0.50 mmol) was dissolved in a mixed solvent of 1,4-dioxane (10 mL) and water (2 mL). 2-Chloropremine-4-amine (65 mg, 0.50 mmol) and sodium carbonate (106 mg, 1 mmol) were added. After nitrogen purging, palladium dichloride bis(triphenylphosphine) (35 mg, 0.05 mmol) was added. The reaction mixture was heated to 80 °C and reacted for 12 hours. The reaction mixture was added to water (30 mL), extracted with ethyl acetate (20 mL x 3), and the organic phase was collected and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: PE / EA = 95 / 5, v / v) to give the title compound of this step (40 mg).

[0773] MS m / z(ESI): 442.2 [M+H] + .

[0774] Step 3: Preparation of 2-(6-chloro-8-(morpholin-3-yl)quinolin-4-yl)pyrimidin-4-amine

[0775] Using a synthetic method similar to that in Example 8, the second step of 3-(1-(5-((tert-butyloxycarbonyl)amino)pyrazin-2-yl)-6-chloro-1H-indazol-4-yl)morpholine-4-carboxylic acid tert-butyl ester was replaced with 3-(4-(4-aminopyrimidin-2-yl)-6-chloroquinoline-8-yl)morpholine-4-carboxylic acid tert-butyl ester, yielding the title compound (35 mg).

[0776] MS m / z(ESI): 342.1 [M+H] + .

[0777] Step 4: Preparation of 1-(3-(4-(4-aminopyrimidin-2-yl)-6-chloroquinoline-8-yl)morpholine)prop-2-en-1-one

[0778] Using a synthetic method similar to that in Example 8, the third step of 5-(6-chloro-4-(morpholin-3-yl)-1H-indazol-1-yl)pyrazin-2-amine was replaced with 2-(6-chloro-8-(morpholin-3-yl)quinolin-4-yl)pyrimidin-4-amine to obtain the title compound (5 mg).

[0779] MS m / z(ESI): 396.1 [M+H] + .

[0780] 1H NMR(400MHz, DMSO-d6)δ9.06(d,J=4.4,1H),8.73(d,J=18.4Hz,1H),8.33(dd,J= 5.6,4.4Hz,1H),7.97(d,J=6.4Hz,1H),7.77-7.61(m,1H),7.22(s,2H),6.96-6.8 1(m,1H),6.55(dd,J=5.6,1.6Hz,1H),6.40-6.22(m,1H),6.13(d,J=16.6Hz,1H), 5.80-5.59(m,1H),4.40-4.23(m,3H),4.05(d,J=11.6Hz,2H),3.29-3.22(m,1H).

[0781] Example 13: Preparation of 1-(3-(6-chloro-4-(1H-pyrazol-4-yl)quinolin-8-yl)morpholino)prop-2-en-1-one (compound 157)

[0782] Step 1: Preparation of tert-butyl 3-(6-chloro-4-(1H-pyrazol-4-yl)quinoline-8-yl)morpholine-4-carboxylic acid

[0783] 3-(6-chloro-4-(((trifluoromethyl)sulfonyl)oxy)quinoline-8-yl)morpholine-4-carboxylic acid tert-butyl ester (0.15 g, 0.30 mmol) was dissolved in a mixed solvent of 1,4-dioxane (4 mL) and water (0.5 mL). 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyl-2-yl)-1H-pyrazole (116 mg, 0.60 mmol) and potassium carbonate (84 mg, 0.6 mmol) were added. After nitrogen purging, methanesulfonic acid [n-butyldi(1-adamantyl)phosphine](2-amino-1,1'-biphenyl-2-yl)palladium (22 mg, 0.03 mmol) was added. The reaction solution was microwaved to 80 °C and reacted for 1 hour. The reaction solution was added to water (20 mL), extracted with ethyl acetate (20 mL x 3), the organic phase was collected, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: PE / EA = 90 / 10, v / v) to obtain the title compound of this step (30 mg).

[0784] MS m / z (ESI): 415.1 [M+H] + .

[0785] Step 2: Preparation of 3-(6-chloro-4-(1H-pyrazol-4-yl)quinoline-8-yl)morpholine

[0786] Using a synthetic method similar to that in Example 8, the second step of 3-(1-(5-((tert-butyloxycarbonyl)amino)pyrazin-2-yl)-6-chloro-1H-indazol-4-yl)morpholine-4-carboxylic acid tert-butyl ester was replaced with 3-(6-chloro-4-(1H-pyrazol-4-yl)quinoline-8-yl)morpholine-4-carboxylic acid tert-butyl ester, yielding the title compound (30 mg).

[0787] MS m / z (ESI): 315.1 [M+H] + .

[0788] Step 3: Preparation of 1-(3-(6-chloro-4-(1H-pyrazol-4-yl)quinolin-8-yl)morpholino)prop-2-en-1-one

[0789] Using a synthetic method similar to that in Example 8, the third step of 5-(6-chloro-4-(morpholin-3-yl)-1H-indazol-1-yl)pyrazin-2-amine was replaced with 3-(6-chloro-4-(1H-pyrazol-4-yl)quinolin-8-yl)morpholine to obtain the title compound (3 mg).

[0790] MS m / z(ESI): 369.1 [M+H] + .

[0791] 1 H NMR (400MHz, DMSO-d6) δ13.42(s,1H),8.92(d,J=4.4Hz,1H),8.38(s,1H),8.13(s,1H),7.99(s,1H),7.64(d,J=4.4Hz,1H),7.00-6.66 (m,2H),6.43-6.20(m,1H),6.13(dd,J=16.4,2.4Hz,1H),5.75-5.56(m,1H),4.40-4.24(m,3H),4.10-3.97(m,2H),3.69-3.52(m,1H).

[0792] Example 14: Preparation of 1-(3-(6-chloro-4-(1H-pyrazol-4-yl)quinolin-8-yl)morpholino)prop-2-en-1-one (compound 155)

[0793] Using a synthetic method similar to that in Example 13, the first step of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)-1H-pyrazole was replaced with 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)-1H-pyrazole to obtain the title compound (4 mg).

[0794] MS m / z(ESI): 369.1 [M+H] + .

[0795] 1 H NMR (400MHz, DMSO-d6) δ13.50 (s, 1H), 8.98 (d, J = 4.4Hz, 1H), 8.07-7.80 (m, 2H), 7.73-7.43 (m, 2H), 7.08-6.68 (m, 2H), 6.4 0-6.21(m,1H),6.13(dd,J=16.4,2.4Hz,1H),5.80-5.56(m,1H),4.41-4.23(m,3H),4.09-3.98(m,2H),3.69-3.50(m,1H).

[0796] Example 15: Preparation of 1-(3-(6-chloro-1-(1H-pyrazolo[3,4-c]pyridin-5-yl)-1H-indazol-4-yl)morpholino)prop-2-en-1-one (compound 149)

[0797] Step 1: Preparation of 5-(4-bromo-6-chloro-1H-indazol-1-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

[0798] Using a synthetic method similar to that of intermediate Example 6, the first-step starting material 5-bromo-N-methylpyrazine-2-amine was replaced with 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine to obtain the title compound (0.5 g).

[0799] MS m / z(ESI): 432.0 [M+H] + .

[0800] Step 2: Preparation of 5-(6-chloro-4-iodo-1H-indazol-1-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

[0801] 5-(4-bromo-6-chloro-1H-indazol-1-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine (400 mg, 0.92 mmol), sodium iodide (278 mg, 1.85 mmol), cuprous iodide (35 mg, 0.18 mmol), and trans-N,N-dimethylcyclohexanediamine (26 mg, 0.18 mmol) were dissolved in 1,4-dioxane (10 mL), and the mixture was then purged with nitrogen and stirred at 110 °C for 12 hours. The reaction mixture was added to water (30 mL) and extracted with EA (20 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure. The solution was purified by column chromatography with silica gel (eluent: PE / EA = 85 / 15, v / v) to give the title compound (0.3 g).

[0802] MS m / z(ESI): 480.0 [M+H] + .

[0803] Step 3: Preparation of tert-butyl 3-(6-chloro-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-1H-indazol-4-yl)morpholine-4-carboxylic acid

[0804] Using a synthetic method similar to that of intermediate Example 11, the first-step starting materials 8-bromo-6-chloroquinoline-4(1H)-one and 4-(tert-butyl)3-(5-methoxy-1,3-dioxoisoindoline-2-yl)morpholine-3,4-dicarboxylate were replaced with 5-(6-chloro-4-iodo-1H-indazol-1-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine and 4-(tert-butyl)3-(1,3-dioxoisoindoline-2-yl)morpholine-3,4-dicarboxylate, respectively, to obtain the title compound (0.2 g).

[0805] MS m / z (ESI): 539.2 [M+H] + .

[0806] Step 4: Preparation of 3-(6-chloro-1-(1H-pyrazolo[3,4-c]pyridin-5-yl)-1H-indazol-4-yl)morpholine

[0807] Using a synthetic method similar to that in Example 8, the second-step starting material 3-(1-(5-((tert-butyloxycarbonyl)amino)pyrazin-2-yl)-6-chloro-1H-indazol-4-yl)morpholine-4-carboxylic acid tert-butyl ester was replaced with 3-(6-chloro-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-1H-indazol-4-yl)morpholine-4-carboxylic acid tert-butyl ester to obtain the title compound (50 mg).

[0808] MS m / z (ESI): 355.1 [M+H] + .

[0809] Step 5: Preparation of 1-(3-(6-chloro-1-(1H-pyrazolo[3,4-c]pyridin-5-yl)-1H-indazol-4-yl)morpholino)prop-2-en-1-one

[0810] Using a synthetic method similar to that in Example 8, the third step of 5-(6-chloro-4-(morpholin-3-yl)-1H-indazol-1-yl)pyrazin-2-amine was replaced with 3-(6-chloro-1-(1H-pyrazolo[3,4-c]pyridin-5-yl)-1H-indazol-4-yl)morpholine to obtain the title compound (5 mg).

[0811] MS m / z (ESI): 409.1 [M+H] + .

[0812] 1 H NMR (400MHz, CDCl3) δ8.84 (s, 1H), 8.70 (t, J = 1.2Hz, 1H), 8.25 (s, 1H), 8.17 ( d,J=22.4Hz,2H),7.65-7.55(m,1H),6.47(dd,J=16.8,10.4Hz,1H),6.36(dd, J=16.8,2.4Hz,1H),6.18-6.00(m,1H),5.72(dd,J=10.0,2.4Hz,1H),4.48(d, J=12.4Hz,1H),4.02-3.92(m,2H),3.63-3.53(m,2H),3.38(t,J=12.4Hz,1H).

[0813] Example 16: Preparation of 1-(2-(4-chloro-2-(1H-pyrazol-4-yl)benzo[d]oxazol-6-yl)-4-(2-methoxyethyl)piperazin-1-yl)prop-2-en-1-one (compound 97)

[0814] Step 1: Preparation of 2-chloro-4,6-diiodoaniline

[0815] o-Chloroaniline (2.02 g, 15.68 mmol), elemental iodine (8.04 g, 31.36 mmol), and silver sulfate (5.43 g, 17.25 mmol) were dissolved in ethanol (50 mL) and stirred at 25 °C for 12 hours. After the reaction was complete, water (100 mL) and ethyl acetate (100 mL x 3) were added for extraction. The organic layer was collected, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography with silica gel (eluent: PE / EA = 4 / 1, v / v) to give the title compound (5.5 g).

[0816] MS m / z (ESI): 379.8 [M+H] +

[0817] Step 2: Preparation of N-(2-chloro-4,6-diiodophenyl)-1-(4-methoxybenzyl)-1H-pyrazole-4-carboxamide

[0818] 2-Chloro-4,6-diiodoaniline (1.3 g, 3.39 mmol) was dissolved in THF (15 mL), and LiHMDS (1 M, 3.73 mL) was added dropwise at 0 °C with stirring for 20 minutes. Then, 1-[(4-methoxyphenyl)methyl]pyrazole-4-carboxyl chloride (1.03 g, 4.07 mmol) was added, and the mixture was stirred at 0 °C for 1 hour. After the reaction was completed, the mixture was quenched with saturated ammonium chloride aqueous solution, extracted with water (100 mL) and ethyl acetate (100 mL x 3), and the organic layer was collected. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography with silica gel (eluent: PE / EA = 4 / 1, v / v) to give the title compound (1.5 g).

[0819] MS m / z(ESI): 594.0 [M+H] + .

[0820] Step 3: Preparation of 4-chloro-6-iodo-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazole

[0821] N-(2-chloro-4,6-diiodophenyl)-1-(4-methoxybenzyl)-1H-pyrazole-4-carboxamide (1.48 g, 2.47 mmol), copper oxide (198.34 mg, 2.47 mmol), and potassium carbonate (1.03 g, 7.41 mmol) were dissolved in DMSO (15 mL), and the mixture was heated to 110 °C and stirred for 16 hours. After the reaction was completed, water (100 mL) and ethyl acetate (100 mL x 3) were added for extraction. The organic layer was collected, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography with silica gel (eluent: DCM / MeOH = 10 / 1, v / v) to give the title compound (1 g).

[0822] MS m / z(ESI): 466.0 [M+H] + .

[0823] Step 4: Preparation of 1-benzyl-4-(tert-butyl)-2-(4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazole-4-yl)benzo[d]oxazol-6-yl)piperazine-1,4-dicarboxylate

[0824] 4-Chloro-6-iodo-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazole (570 mg, 1.21 mmol), 1-benzyl-4-(tert-butyl)-2-(1,3-dioxoisoindoline-2-yl)piperazine-1,2,4-tricarboxylate (802.65 mg, 1.58 mmol), 5-methoxypicolinimidine hydrochloride (45.93 mg, 242.36 μmol), nickel chloride dimethoxyethane (53.79 mg, 242.36 μmol), tetrabutylammonium iodide (452.12 mg, 1.21 mmol), and zinc powder (778.37 mg, 12.12 mmol) were dissolved in DMAC (15 mL), purged with nitrogen three times, and stirred at 25 °C for 2 hours. After the reaction was completed, zinc powder was filtered through diatomaceous earth, and water (100 mL) and ethyl acetate (100 mL x 3) were added for extraction. The organic layer was collected, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography with silica gel (eluent: PE / EA = 2 / 1, v / v) to obtain the title compound (720 mg).

[0825] MS m / z (ESI): 658.2 [M+H] + .

[0826] Step 5: Preparation of benzyl 2-(4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazol-6-yl)piperazine-1-carboxylate

[0827] 1-Benzyl-4-(tert-butyl)-2-(4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazol-6-yl)piperazine-1,4-dicarboxylate (700 mg, 1.05 mmol) was dissolved in DCM (12.00 mL), and TFA (3 mL) was added. The mixture was stirred at 25 °C for 2 hours. After the reaction was completed, the excess solvent was removed by concentration. The pH was adjusted to 7-8 by adding saturated sodium bicarbonate aqueous solution under ice bath conditions. The mixture was extracted with water (100 mL) and ethyl acetate (100 mL x 3). The organic layer was collected, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound (520 mg).

[0828] MS m / z (ESI): 558.2 [M+H] + .

[0829] Step 6: Preparation of 2-(4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazol-6-yl)-4-(2-methoxyethyl)piperazine-1-carboxylic acid benzyl ester

[0830] 2-(4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazol-6-yl)piperazine-1-carboxylic acid benzyl ester (100 mg, 177.41 μmol), 2-bromoethyl methyl ether (37.36 mg, 266.12 μmol), and potassium carbonate (74.19 mg, 532.23 μmol) were dissolved in acetonitrile (5 mL), and the mixture was heated to 80 °C and stirred for 3 hours under microwave. After the reaction was completed, water (100 mL) and ethyl acetate (100 mL x 3) were added for extraction. The organic layer was collected, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound (90 mg).

[0831] MS m / z (ESI): 616.2 [M+H] + .

[0832] Step 7: Preparation of 4-chloro-6-(4-(2-methoxyethyl)piperazin-2-yl)-2-(1H-pyrazol-4-yl)benzo[d]oxazole

[0833] 2-(4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazole-4-yl)benzo[d]oxazol-6-yl)-4-(2-methoxyethyl)piperazine-1-carboxylic acid benzyl ester (90 mg, 145.87 μmol) was dissolved in TFA (5 mL) and stirred at 80 °C for 2 hours. After the reaction was completed, the excess solvent was removed by concentration, and the pH was adjusted to 8 by adding saturated sodium bicarbonate solution under ice bath conditions. The mixture was extracted with ethyl acetate (20 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound (40 mg).

[0834] MS m / z(ESI): 362.1 [M+1] + .

[0835] Step 8: Preparation of 1-(2-(4-chloro-2-(1H-pyrazol-4-yl)benzo[d]oxazol-6-yl)-4-(2-methoxyethyl)piperazin-1-yl)prop-2-en-1-one

[0836] 4-Chloro-6-(4-(2-methoxyethyl)piperazin-2-yl)-2-(1H-pyrazol-4-yl)benzo[d]oxazole (20 mg, 55.27 μmol) and N,N-diisopropylethylamine (6.48 mg, 49.75 μmol) were dissolved in dichloromethane (3 mL), and 2-acryloyl chloride (2.27 mg, 24.87 μmol) was added dropwise. The mixture was stirred at 25 °C for 20 minutes. After the reaction was completed, the solvent was removed under reduced pressure, and the title compound (3.98 mg) was obtained by reverse-phase separation and purification.

[0837] MS m / z (ESI): 416.1 [M+H] + .

[0838] 1 H NMR (400MHz, DMSO-d6) δ13.61(s,1H),8.44(s,2H),7.84(s,1H),7.60-7.39(m,1H),6.89(s,1H),6.22(d,J=16.4Hz,1H),5.76(dd,J=10. 4,2.4Hz,2H),3.70-3.42(m,4H),3.30(s,3H),3.14-2.97(m,1H),2.95-2.84(m,1H),2.58(s,1H),2.47-2.26(m,2H),2.20-2.06(m,1H).

[0839] Example 17: Preparation of 1-(2-(4-chloro-2-(1H-pyrazol-4-yl)benzo[d]oxazol-6-yl)-4-(2-methoxyethyl)piperazin-1-yl)prop-2-en-1-one (compound 163)

[0840] Step 1: Preparation of 6-chloro-1-(6-chloropyrimidin-4-yl)-4-iodo-1H-indazole

[0841] 6-Chloro-4-iodo-1H-indazole (2.69 g, 9.57 mmol) was dissolved in DMF (20 mL), cooled to below -20 °C in a dry ice bath, and sodium hydride (573.91 mg, 14.35 mmol) was added. After stirring for 20 minutes, 4,6-dichloropyrimidine (1.5 g, 9.57 mmol) was added, and the mixture was stirred at this temperature for 2 hours. After the reaction was complete, saturated ammonium chloride aqueous solution was added to quench the reaction. The mixture was extracted with ethyl acetate (100 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The solid was then slurried with a mixed solvent (ethyl acetate / methanol = 1 / 1, v / v, 100 mL), filtered, collected, and dried to give the title compound (3 g).

[0842] MS m / z(ESI): 399.9 [M+H] + .

[0843] Step 2: Preparation of 6-(6-chloro-4-iodo-1H-indazol-1-yl)-N,N-bis(2,4-dimethoxybenzyl)pyrimidine-4-amine

[0844] 6-Chloro-1-(6-chloropyrimidin-4-yl)-4-iodo-1H-indazole (1.5 g, 3.64 mmol), potassium carbonate (1.52 g, 10.93 mmol), and bis(2,4-dimethoxybenzyl)amine (1.40 g, 4.37 mmol) were dissolved in DMAC (20 mL), heated to 100 °C, and stirred for 2 hours. After the reaction was complete, water (100 mL) was added to dilute the solution, the mixture was filtered, and the filter cake was washed with methanol. The solid was dried to give the title compound (2 g).

[0845] MS m / z (ESI): 672.2 [M+H] + .

[0846] Step 3: Preparation of 1-benzyl-4-(tert-butyl)-2-(1-(6-(bis(2,4-dimethoxybenzyl)amino)pyrimidin-4-yl)-6-chloro-1H-indazole-4-yl)piperazine-1,4-dicarboxylate

[0847] 6-(6-chloro-4-iodo-1H-indazol-1-yl)-N,N-bis(2,4-dimethoxybenzyl)pyrimidin-4-amine (1.3 g, 1.92 mmol), 1-benzyl-4-(tert-butyl)-2-(1,3-dioxoisoindolin-2-yl)piperazine-1,2,4-tricarboxylate (1.28 g, 2.49 mmol), nickel chloride dimethoxyethane (42.37 mg, 191.54 μmol), 5-methoxypicolinimidine hydrochloride (72.36 mg, 383.09 μmol), tetrabutylammonium iodide (714.65 mg, 1.92 mmol), and zinc powder (1.22 g, 19.15 mmol) were dissolved in DMAC (400 mL), purged with nitrogen, and stirred at 25 °C for 2 hours. After the reaction was complete, zinc powder was filtered through iodine-diatomaceous earth and extracted with water (1 L) and ethyl acetate (100 mL x 3). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography with silica gel (eluent: PE / EA = 1 / 1, v / v) to give the title compound (800 mg).

[0848] MS m / z (ESI): 864.3 [M+H] + .

[0849] Step 4: Preparation of benzyl 2-(6-chloro-1-(6-((2,4-dimethoxybenzyl)amino)pyrimidin-4-yl)-1H-indazol-4-yl)piperazine-1-carboxylate

[0850] 1-Benzyl-4-(tert-butyl)-2-(1-(6-(bis(2,4-dimethoxybenzyl)amino)pyrimidin-4-yl)-6-chloro-1H-indazole-4-yl)piperazine-1,4-dicarboxylate (800 mg, 925.52 μmol) was dissolved in TFA (3 mL) and dichloromethane (15 mL) and stirred at 25 °C for 1 hour. After the reaction was completed, the excess solvent was removed by concentration, and the pH was adjusted to 8 by adding saturated sodium bicarbonate solution under ice bath. Extraction was performed with ethyl acetate (50 mL x 3). The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography with silica gel (eluent: DCM / MeOH = 2 / 1, v / v) to give the title compound (350 mg).

[0851] MS m / z (ESI): 614.3 [M+H] + .

[0852] Step 5: Preparation of benzyl 2-(6-chloro-1-(6-((2,4-dimethoxybenzyl)amino)pyrimidin-4-yl)-1H-indazol-4-yl)-4-(2-methoxyethyl)piperazine-1-carboxylate

[0853] Using a synthetic method similar to that in Example 16, the starting material in step 6, 2-(4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazol-6-yl)piperazine-1-carboxylic acid benzyl ester, was replaced with 2-(6-chloro-1-(6-(((2,4-dimethoxybenzyl)amino)pyrimidin-4-yl)-1H-indazol-4-yl)piperazine-1-carboxylic acid benzyl ester to obtain the crude product of the title compound (70 mg).

[0854] MS m / z (ESI): 672.3 [M+H] + .

[0855] Step 6: Preparation of 6-(6-chloro-4-(4-(2-methoxyethyl)piperazin-2-yl)-1H-indazol-1-yl)pyrimidine-4-amine

[0856] Using a synthetic method similar to that in Example 16, the starting material in step 7, 2-(4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazol-6-yl)-4-(2-methoxyethyl)piperazine-1-carboxylic acid benzyl ester, was replaced with 2-(6-chloro-1-(6-(((2,4-dimethoxybenzyl)amino)pyrimidin-4-yl)-1H-indazol-4-yl)-4-(2-methoxyethyl)piperazine-1-carboxylic acid benzyl ester, yielded the crude product of the title compound (15 mg).

[0857] MS m / z(ESI): 388.2 [M+H] + .

[0858] Step 7: Preparation of 1-(2-(1-(6-aminopyrimidin-4-yl)-6-chloro-1H-indazol-4-yl)-4-(2-methoxyethyl)piperazin-1-yl)prop-2-en-1-one

[0859] Using a synthetic method similar to that in Example 16, the starting material 4-chloro-6-(4-(2-methoxyethyl)piperazin-2-yl)-2-(1H-pyrazol-4-yl)benzo[d]oxazole in step 8 was replaced with 6-(6-chloro-4-(4-(2-methoxyethyl)piperazin-2-yl)-1H-indazol-1-yl)pyrimidine-4-amine to obtain the title compound (4.40 mg).

[0860] MS m / z(ESI): 442.0 [M+H] + .

[0861] 1 H NMR(400MHz,DMSO-d6)δ8.79(d,J=1.6Hz,1H),8.53-8.36(m,2H),8.06(s,1H), 7.15(s,2H),6.93(s,1H),6.85(dd,J=16.4,10.0Hz,1H),6.24(dd,J=16.4,2.4H z,1H),6.14(s,1H),5.76(dd,J=10.4,2.4Hz,1H),3.66-3.52(m,3H),3.31(s,3 H),3.10-2.90(m,2H),2.75-2.57(m,2H),2.48-2.36(m,2H),2.21-2.10(m,1H).

[0862] Example 18: Preparation of 2-(4-acryloyl-3-(1-(6-aminopyrimidin-4-yl)-6-chloro-1H-indazol-4-yl)piperazin-1-yl)acetonitrile (compound 161)

[0863] Using a synthetic method similar to that in Example 17, the starting material 2-bromoethylmethyl ether in step 5 was replaced with bromoacetonitrile to obtain the title compound (2.04 mg).

[0864] MS m / z (ESI): 423.1 [M+H] + .

[0865] 1 H NMR(400MHz, DMSO-d6)δ8.80(s,1H),8.47-8.34(m,2H),7.80-7.57(m,1H),7.16(s,2H),6.96-6.82(m,2H),6.26(dd,J=16.4,2.4Hz,2H),5.7 8(dd,J=10.4,2.2Hz,1H),4.11-3.81(m,3H),3.61-3.48(m,1H),3.17- 3.05(m,1H),2.95-2.88(m,1H),2.70-2.56(m,1H),2.33-2.27(m,1H).

[0866] Example 19: Preparation of 1-(2-(1-(6-aminopyrimidin-4-yl)-6-chloro-1H-indazol-4-yl)-4-(2,2,2-trifluoroethyl)piperazin-1-yl)prop-2-en-1-one (compound 159)

[0867] Using a synthetic method similar to that in Example 17, the starting material 2-bromoethylmethyl ether in step 5 was replaced with 2,2,2-trifluoroethyltrifluoromethanesulfonate to obtain the title compound (9.22 mg).

[0868] MS m / z(ESI): 466.0 [M+H] + .

[0869] 1 H NMR (400MHz, DMSO-d6) δ8.80(s,1H),8.41(d,J=18.4Hz,2H),7.91(s,1H),7.16(s,2H),6.93(s,1H),6.85(dd,J=15.6,11.6Hz,1H),6.31-6.08(m,2 H),5.77(dd,J=10.4,2.4Hz,1H),4.07-3.86(m,1H),3.62-3.52(m,1H),3. 33-3.29(m,1H),3.15-2.96(m,2H),2.91-2.77(m,1H),2.49-2.41(m,2H).

[0870] Example 20: Preparation of 1-(3-(1-(4-amino-1,3,5-triazin-2-yl)-6-chloro-1H-indol-4-yl)morpholino)prop-2-en-1-one (compound 119)

[0871] Step 1: Preparation of 4-(4-bromo-6-chloro-1H-indol-1-yl)-N,N-bis(2,4-dimethoxybenzyl)-1,3,5-triazine-2-amine

[0872] 4-Bromo-6-chloro-1H-indole (200 mg, 859.04 μmol) was dissolved in DMF (20 mL), and sodium hydride (51.54 mg, 1.29 mmol) was added at 25 °C. After stirring for 20 minutes, 4-chloro-N,N-bis(2,4-dimethoxybenzyl)-1,3,5-triazine-2-amine (448.66 mg, 1.03 mmol) was added, and the mixture was stirred at 25 °C for 2 hours. After the reaction was complete, the reaction was quenched with saturated ammonium chloride aqueous solution. The mixture was extracted with ethyl acetate (100 mL x 3), and the organic layer was collected, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography with silica gel (eluent: PE / EA = 1 / 1, v / v) to give the title compound (500 mg).

[0873] MS m / z (ESI): 624.2 [M+H] + .

[0874] Step 2: Preparation of tert-butyl 3-(1-(4-(bis(2,4-dimethoxybenzyl)amino)-1,3,5-triazin-2-yl)-6-chloro-1H-indol-4-yl)morpholine-4-carboxylic acid

[0875] Using a synthetic method similar to that in Example 16, the starting materials in step 4, 4-chloro-6-iodo-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazole and 1-benzyl-4-(tert-butyl)-2-(1,3-dioxoisoindoline-2-yl)piperazine-1,2,4-tricarboxylate, were replaced with 4-(4-bromo-6-chloro-1H-indoline-1-yl)-N,N-bis(2,4-dimethoxybenzyl)-1,3,5-triazine-2-amine and 4-(tert-butyl)3-(5-methoxy-1,3-dioxoisoindoline-2-yl)morpholine-3,4-dicarboxylate, respectively, to obtain the title compound (300 mg).

[0876] MS m / z (ESI): 731.3 [M+H] + .

[0877] Step 3: Preparation of 4-(6-chloro-4-(morpholin-3-yl)-1H-indol-1-yl)-1,3,5-triazine-2-amine

[0878] Using a synthetic method similar to that in Example 16, the starting material 2-(4-chloro-2-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)benzo[d]oxazol-6-yl)-4-(2-methoxyethyl)piperazine-1-carboxylic acid benzyl ester in step 7 was replaced with 3-(1-(4-(bis(2,4-dimethoxybenzyl)amino)-1,3,5-triazine-2-yl)-6-chloro-1H-indol-4-yl)morpholine-4-carboxylic acid tert-butyl ester to obtain the crude product of the title compound (60 mg).

[0879] MS m / z(ESI): 331.2 [M+1] + .

[0880] Step 4: Preparation of 1-(3-(1-(4-amino-1,3,5-triazin-2-yl)-6-chloro-1H-indol-4-yl)morpholino)prop-2-en-1-one

[0881] Using a synthetic method similar to that in Example 16, the starting material in step 8, 4-chloro-6-(4-(2-methoxyethyl)piperazin-2-yl)-2-(1H-pyrazol-4-yl)benzo[d]oxazole, was replaced with 4-(6-chloro-4-(morpholin-3-yl)-1H-indol-1-yl)-1,3,5-triazine-2-amine to obtain the title compound (7.33 mg).

[0882] MS m / z(ESI): 385.0 [M+H] + .

[0883] 1 H NMR(400MHz, DMSO-d6)δ8.86(d,J=1.6Hz,1H),8.53(s,1H),8.19(d,J=3.6H z,1H),7.98(s,1H),7.87(s,1H),7.64-7.39(m,1H),6.90(s,1H),6.86-6.68 (m,1H),6.22(dd,J=16.4,2.4Hz,1H),5.89(s,1H),5.74(d,J=10.4Hz,1H), 4.47-4.26(m,1H),4.03-3.69(m,3H),3.58-3.46(m,1H),3.28-3.20(m,1H).

[0884] Example 21: Preparation of 1-(2-(1-(5-aminopyrazin-2-yl)-6-chloro-1H-indazol-4-yl)-4,4-difluoropiperidin-1-yl)prop-2-en-1-one (compound 199)

[0885] Using a synthetic method similar to that in Example 8, the first-step starting material 3-(6-chloro-1H-indazol-4-yl)morpholin-4-carboxylic acid tert-butyl ester was replaced with 2-(6-chloro-1H-indazol-4-yl)-4,4-difluoropiperidine-1-carboxylic acid tert-butyl ester to obtain the title compound (4 mg).

[0886] MS m / z (ESI): 419.1 [M+H] + .

[0887] 1 H NMR (400MHz, DMSO-d6) δ8.52(d,J=1.6Hz,1H),8.44(d,J=0.8Hz,1H),8.30(d,J=1.6Hz,1H),7.87(d,J=1.6Hz,1H),7.07(s,1H),6.94- 6.84(m,1H),6.65(s,2H),6.24-6.18(m,2H),5.77(d,J=10.4Hz,1H),4.43(s,1H),2.90(s,1H),2.71-2.64(m,2H),2.23-2.11(m,2H).

[0888] Example 22: Preparation of 6-(4-(1-acryloyl-4-(difluoromethylene)piperidin-2-yl)-6-chloro-1H-indazol-1-yl)pyrimidin-4(3H)-one (compound 203)

[0889] Using a synthetic method similar to that in Example 8, the first-step raw material 3-(6-chloro-1H-indazol-4-yl)morpholin-4-carboxylic acid tert-butyl ester was replaced with 1-(tert-butyl)-2-methyl-4-(difluoromethylene)piperidine-1,2-dicarboxylic acid ester and (5-bromopyrazin-2-yl)carbamate tert-butyl ester was replaced with 4-chloro-6-((4-methoxybenzyl)oxy)pyrimidine to obtain the title compound (3 mg).

[0890] MS m / z (ESI): 432.1 [M+H] + .

[0891] 1H NMR (400MHz, DMSO-d6) δ12.45(s,1H),8.69(s,1H),8.44(d,J=12Hz,2H),7.16(s,1H),6.91(s,1H),6.64(s,1H),6.29-6.08(m,2H),5 .76(s,1H),4.04(s,1H),3.14(t,J=12Hz,1H),2.93(dd,J=15.2,4.4Hz,1H),2.68(s,1H),2.42(d,J=15.2Hz,1H),2.31-2.17(m,1H).

[0892] Example 23: Preparation of 6-(4-(1-acryloyl-4,4-difluoropiperidin-2-yl)-6-chloro-1H-indazol-1-yl)pyrimidin-4(3H)-one (compound 201)

[0893] Using a synthetic method similar to that in Example 8, the first-step starting material 3-(6-chloro-1H-indazol-4-yl)morpholin-4-carboxylic acid tert-butyl ester was replaced with 2-(6-chloro-1H-indazol-4-yl)-4,4-difluoropiperidin-1-carboxylic acid tert-butyl ester and (5-bromopyrazin-2-yl)carbamate tert-butyl ester was replaced with 4-chloro-6-((4-methoxybenzyl)oxy)pyrimidine to obtain the title compound (3 mg).

[0894] MS m / z (ESI): 420.1 [M+H] + .

[0895] 1 H NMR (400MHz, DMSO-d6) δ12.77(s,1H),8.69(d,J=1.6Hz,1H),8.60(s,1H),8.46(s,1H),7.17(s,1H),6.90(s,1H),6.6 6(s,1H),6.25-6.1...

Claims

1. A compound, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite, prodrug, or pharmaceutically acceptable salt or ester thereof, wherein said compound has a structure as shown in formula (I): in, Ring A is selected from 3-12 membered carbon rings, 3-12 membered heterocycles, and C. 6-10 Aromatic rings and 5-10 heterocyclic aromatic rings; R 1 Selected from C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, the C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Each alkynyl group is independently and optionally replaced by one or more substituents selected from H, deuterium, CN and halogens; X 1 Selected from O, S (=O)2, -C (=C) 1-6 alkyl)-, -C(=C 1-6 (halogenated alkyl)-, CR 5 R 6 and NR 7 ; X 2 Selected from N and CR 3 ; R 2 Each is independently selected from H, halogen, OH, C 1-6 Alkyl, C 2-6 alkenyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl groups and -C(=O)-(CH2) p -NR a R b The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl groups and -C(=O)-(CH2) p -NR a R b Each is independently and optionally influenced by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6- 10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR 5 R 6 Substituents are replaced by; and / or, Two Rs 2 The atoms or R connected to it 2 R 7 The atoms connected to it together form C 3-10 Cycloalkyl, 3-12-membered heterocyclic or 5-10-membered heteroaryl, wherein the C 3-10 The cycloalkyl, 3-12-membered heterocyclic and 5-10-membered heteroaryl groups are each independently and optionally separated by one or more elements selected from halogen, H, OH, CN, -NR. 5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OC 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Substituents of aryl and 5-10 heteroaryl groups; R 3 Each is independently selected from H, halogens, CN, OH, NO2, -NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, carboxyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, oxo groups, thio groups, C 3-10 cycloalkyl, -OC 3-10 Cycloalkyl and 3-12 membered heterocyclic groups, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, carboxyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, oxo groups, thio groups, C 3-10 cycloalkyl, -OC 3-10 The cycloalkyl group and the 3-12 membered heterocyclic group are each independently and optionally surrounded by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl groups, -C(=O)-OH, NO2, and -NR 5 R 6 The substituents are replaced; R 4 Selected from H, deuterium, halogen, oxo group, thio group, CN, OR 7 SR 7 S(=O)R 7 S(=O)2R 7 NO2, -NR 5 R 6 -NR 7 S(=O)2R c -S(=O)2NR 5 R 6 -C(=O)R 7 -C(=O)OR 7 -C(=O)NR 5 R 6 -OC(=O)NR 5 R 6 -NR 7 C(=O)2R c -NR 7 C(=O)2NR 5 R 6 -NR 7 C(=O)2OR c C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl and 3-12 membered heterocyclic, wherein the C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 alkenyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, C 3- 10 cycloalkyl, C 6-10 The aryl, 5-10 membered heteroaryl, and 3-12 membered heterocyclic groups are each independently and optionally bound by one or more groups selected from H, halogen, OH, CN, -COOH, oxo, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Hydroxyalkyl, C 3- 10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-10 cycloalkyl, -NR 5 R 6 Substituents are replaced by; and / or, Two Rs 4 The atoms connected to it together form C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl or 5-10 heteroaryl, wherein the C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more elements selected from H, halogen, OH, CN, -NR. 5 R 6 Oxide group, thio group, -C(=O)NR 5 R 6 C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -OC 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Substituents of aryl and 5-10 heteroaryl groups; R 5 R 6 and R 7 Each is independently selected from H, halogen, OH, CN, C 1-6 Alkyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-12 membered heterocyclic group, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-12 membered heterocyclic group, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR a R b -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR a R b The substituents are replaced; Or, R 5 and R 6 The atoms connected to it together form C 3-10 Cycloalkyl or 3-12-membered heterocyclic group, wherein the C3-10 cycloalkyl and 3-12-membered heterocyclic group are each optionally and independently composed of one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR a R b -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR a R b The substituents are replaced; R a and R b Each is independently selected from H and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Heteroalkyl, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Heteroalkyl, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more elements selected from H, halogen, OH, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 3-10 Substituents of cycloalkyl groups; R c Selected from H, OH, halogens, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 1-6 Haloalkyl, C 1- 6-alkoxy, C 1-6 Halogenated alkoxy groups, C 3-10 Cycloalkyl, 3-12 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2- 6-alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1- 6-alkyl, -S(=O)2-C 6-10 Aryl, -C(=O)NR 5 R 6 -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR 5 R 6 The substituents are replaced; p is selected from 0, 1, 2, 3, 4, 5, and 6; m and n are each independently selected from 0, 1, 2, 3 and 4.

2. The compound of claim 1, or its stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or their metabolites, prodrugs, or pharmaceutically acceptable salts or esters, wherein, Ring A is selected from 3-12-membered heterocycles and 5-10-membered heteroaromatic rings, wherein the 3-12-membered heterocycles and 5-10-membered heteroaromatic rings contain one, two or three heteroatoms selected from N, O and / or S.

3. The compound of any one of claims 1-2, or its stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or their metabolites, prodrugs, or pharmaceutically acceptable salts or esters, wherein, X 2 Selected from N and CH.

4. The compound of any one of claims 1-3, or its stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or their metabolites, prodrugs, or pharmaceutically acceptable salts or esters, wherein, The compound has a structure as shown in formula (I-1'): q is selected from 0, 1, 2, and 3; X 3 X 4 X 5 and X 6 Each is independently selected from N and NR. 7 O, S, S(=O)2, CR 5 R 6 and CR 4 ;X 1 X 2 R 1 R 2 R 3 R 4 R 5 R 6 R 7 m and n are as defined in any one of claims 1-3.

5. The compound of any one of claims 1-4, or its stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or their metabolites, prodrugs, or pharmaceutically acceptable salts or esters, wherein, Selected from 5-6 member heteroaryl groups containing N, O and / or S atoms and 3-6 member heterocyclic groups containing N, O and / or S atoms.

6. The compound of any one of claims 1-5, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite, prodrug, or pharmaceutically acceptable salt or ester thereof, wherein, The compound has any of the following characteristics: (1)X 3 For O, X 4 For CH and CH2, X 5 Selected from N and NH, X 6 Selected from O, S, CH and CH2; (2)X 3 Selected from N and NH, X 4 Selected from CH and CH2, X 5 Selected from N and NH, X 6 Selected from O, S, CH and CH2; (3)X 3 Selected from CH and CH2, X 4 Selected from N and NH, X 5 Selected from N and NH, X 6 Selected from O, S, CH and CH2; (4)X 3 Selected from N and NH, X 4 Selected from CH and CH2, X 5 Selected from CH and CH2, X 6 Selected from O, S, CH and CH2; (5)X 3 Selected from N and NH, X 4 Selected from CH and CH2, X 5 For O, X 6 Selected from O, S, CH and CH2; (6)X 3 Selected from CH and CH2, X 4 Selected from N and NH, X 5 Selected from CH and CH2, X 6 Selected from O, S, CH and CH2; (7)X 3 For O, X 4 Selected from N and NH, X 5 Selected from CH and CH2, X 6 Selected from O, S, CH and CH2; (8)X 3 For O, X 4 Selected from CH and CH2, X 5 Selected from CH and CH2, X 6 Selected from O, S, CH and CH2; (9)X 3 Selected from N and NH, X 4 Selected from CH and CH2, X 5 Let S and X be the values ​​of S and X. 6 Selected from O, S, CH and CH2; (10)X 3 Selected from CH and CH2, X 4 Selected from CH and N, X 5 Selected from NH, CH and CH2, X 6 Selected from O, S, CH and CH2; (11)X 3 Selected from CH and CH2, X 4 Selected from CH and CH2, X 5 For N and NH, X 6 Selected from O, S, CH and CH2; (12)X 3 Selected from S, X 4 Selected from NH and N, X 5 For CH and CH2, X 6 Selected from O, S, CH and CH2; (13)X 3 Selected from N and NH, X 4 Selected from NH and N, X 5 For NH and N, X 6 Selected from O, S, CH and CH2; (14)X 3 Selected from S, X 4 Selected from CH and CH2, X 5 For NH and N, X 6 Selected from O, S, CH and CH2; (15)X 3 Let S and X be the values ​​of S and X. 4 Selected from N and CH, X 5 Selected from CH and N, X 6 Selected from O, S, CH and CH2; (16)X 3 Selected from S, X 4 Selected from CH and CH2, X 5 For CH and CH2, X 6 Selected from O, S, CH and CH2; (17)X 3 Let N, X 4 Selected from N and CH, X 5 Selected from NH, X 6 Selected from O, S, CH and CH2.

7. The compound of any one of claims 1-6, or its stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or their metabolites, prodrugs, or pharmaceutically acceptable salts or esters, in, R 1 Selected from C 2-6 alkenyl and C 1-6 Haloalkyl, the C 2-6 alkenyl and C 1-6 Each haloalkyl group is optionally and independently replaced by one or more substituents selected from H, deuterium, CN and halogens.

8. The compound of any one of claims 1-7, or its stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or their metabolites, prodrugs, or pharmaceutically acceptable salts or esters, in, R 1 Selected from vinyl, -CH2-CHCl2 and -CHCl2.

9. The compound of any one of claims 1-8, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite, prodrug, or pharmaceutically acceptable salt or ester thereof, wherein, X 1 Selected from O, -C (=C) 1-6 (halogenated alkyl)-, CR 5 R 6 and NR 7 .

10. The compound of any one of claims 1-9, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite, prodrug, or pharmaceutically acceptable salt or ester thereof. in, R 5 R 6 and R 7 Each is independently selected from H, halogen, OH, CN, C 1-6 Alkyl, C 3-10 cycloalkyl, C 1- 6-Hydroalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl, the C 1-6 Alkyl, C 3-10 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Hydroxyalkyl, -C(=O)R c -S(=O)R c -S(=O)2R c -C(=O)-(CH2) p -NR a R b 3-10 membered heterocyclic groups, C 6-10 The aryl group and the 5-10 heteroaryl group are each independently and optionally bonded by one or more groups selected from H, deuterium, oxo, thio, halogen, OH, CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-10 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic, C 1-6 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-6 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-6 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)NR a R b -C(=O)-C 1-6 Alkyl group, -OC(=O)-C 1-6 Alkyl, -C(=O)-OC 1-6 Alkyl, NO2 and -NR a R b The substituents are replaced by the substituents.

11. The compound of any one of claims 1-10, or its stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or their metabolites, prodrugs, or pharmaceutically acceptable salts or esters, in, R 2 Each is independently selected from H, halogen, OH, C 1-4 Alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups and C 1-4 hydroxyalkyl, the C 1-4 Alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups and C 1-4 Each hydroxyalkyl group is independently and optionally marked by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C. 1-4 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1- 4-Hydroalkyl, C 3-6 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-6 membered heterocyclic, C 1-4 Alkoxy, -OC 6-10 Aryl, -SC 6-10 Aryl, -S(=O)-C 1-4 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-4 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)-C 1-4 Alkyl group, -OC(=O)-C 1-4 Alkyl groups and -C(=O)-OC 1-4 Substituents of alkyl groups; And / or, R 2 R 7 The atoms connected to it together form an imidazole group, which is optionally substituted with one or more methyl groups.

12. The compound of any one of claims 1-11, or its stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or their metabolites, prodrugs, or pharmaceutically acceptable salts or esters, in, R 3 Each is independently selected from H, halogens, CN, OH, NO2, and C. 1-4 Alkyl, C 1-6 Alkoxy, carboxyl, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, oxo groups, thio groups, C 3-6 cycloalkyl, -OC 3-8 Cycloalkyl and 3-6 membered heterocyclic groups, wherein the C 1-4 Alkyl, C 1-4 Alkoxy, carboxyl, C 1-4 Haloalkyl, C 1-4 Halogenated alkoxy groups, oxo groups, thio groups, C 3-6 cycloalkyl, -OC 3-6 The cycloalkyl group and the 3-6 membered heterocyclic group are each independently and optionally surrounded by one or more groups selected from H, deuterated, oxo, thio, halogen, OH, CN, C. 1-4 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-4 Haloalkyl, C 3-6 cycloalkyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-6 membered heterocyclic, C 1-4 Alkoxy, -OC 6-10 Aryl, -SC 6- 10 Aryl, -S(=O)-C 1-4 Alkyl, -S(=O)-C 6-10 Aryl, -S(=O)2-C 1-4 Alkyl group, -S(=O)2-C 6-10 Aryl, -C(=O)-C 1-4 Alkyl group, -OC(=O)-C 1-4 Alkyl, -C(=O)-OC 1-4 It is replaced by alkyl groups and -C(=O)-OH substituents.

13. The compound of any one of claims 1-12, or its stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or their metabolites, prodrugs, or pharmaceutically acceptable salts or esters, in, R 4 Selected from C 1-4 Alkyl, -NR 5 R 6 -C(=O)NR 5 R 6 5-10-membered heteroaryl and 3-10-membered heterocyclic group, wherein each of the 5-10-membered heteroaryl and 3-10-membered heterocyclic group is optionally and independently composed of one or more groups selected from C 1-6 Alkyl, oxo, OH, C 1-6 Alkoxy, C 3-8 cycloalkyl, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, -OC 3-8 cycloalkyl and -NR 5 R 6 Substituents are replaced by; and / or, Two Rs 4 The atoms bonded to it together form a 5-10 membered heteroaryl group or a 5-10 membered heterocyclic group, wherein the 5-10 membered heteroaryl group and the 5-10 membered heterocyclic group are optionally composed of one or more atoms selected from -NR 5 R 6 It is replaced by substituents of oxo groups.

14. The compound of any one of claims 1-13, or its stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or their metabolites, prodrugs, or pharmaceutically acceptable salts or esters, in, R 5 R 6 Each is independently selected from H, halogen, C 1-4 Alkyl, C 3-6 cycloalkyl and 5-6-membered heteroaryl, the C 1-4 Alkyl, C 3-6 The cycloalkyl group and the 5-6-membered heteroaryl group are each independently and optionally separated by one or more groups selected from C. 1-4 Alkyl, C 3-6 cycloalkyl, fluorinated C 1-4 Alkyl and chlorinated C 1-4 Alkyl groups are substituted.

15. The compound of any one of claims 1-14, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite, prodrug, or pharmaceutically acceptable salt or ester thereof, wherein, The compound has one or more of the following characteristics: (1)X 1 Selected from O, -C (=CF2)-, -C (=CCl2)- and NR 7 R 7 Each was independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy-C 1-4 Alkyl-, -C 1-4 Alkyl-CN, -C(=O)C 1-4 Alkyl, 3-6 membered heterocyclic and 5-10 membered heteroaryl; (2)R 2 For H and halogens; or, R 2 R 7 The atoms connected to it together form an imidazole group, which is optionally replaced by one or more methyl groups; (3)R 3 Each is independently selected from H and halogens; (4)R 4 Selected from methyl, NH2, -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyridinyl, pyrazinyl, triazole, oxazolyl, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3, wherein -C(=O)NH2, -C(=O)NH-CH3, -C(=O)NH-cyclopropyl, pyrazolyl, morpholinyl, pyrimidinyl, pyridyl, pyrazinyl, triazole, oxazolyl, -NH-pyrimidinyl-CH3, -NH-pyrimidinyl-cyclopropyl, -NH-pyrimidinyl-cyclobutyl, and -NH-pyrimidinyl-CF3 are optionally and independently composed of one or more compounds selected from CH3, NH2, -NH-CH3, -NH-cyclopropyl, -NH-pyridinyl-CH3, -NH-pyridinyl-cyclopropyl, -NH-pyridinyl-cyclobutyl, -NH-pyridinyl-CF3, methoxy, trifluoromethoxy, -O-cyclopropyl, triazole, and Substituents are replaced by; and / or, Two Rs 4 The atoms connected to it together form a 5-6 membered heteroaryl or a 3-6 membered heterocyclic group, wherein each of the 5-6 membered heteroaryl and the 3-6 membered heterocyclic group is optionally and independently replaced by one or more substituents selected from oxo groups and -NH2. (5)R 7 Each was independently selected from C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy-C 1-4 Alkyl-, -C 1-4 Alkyl-CN, -C(=O)C 1-4 Alkyl groups, 3-6 membered heterocyclic groups (e.g., 3-6 membered heterocyclic groups containing N, O and / or S atoms), and 5-10 membered heteroaryl groups; (6)R 5 R 6 Each is independently selected from H, methyl, cyclopropyl, -pyrimidin-CH3, -pyrimidin-cyclopropyl, -pyrimidin-cyclobutyl, -pyrimidin-CF3 and pyrazolyl; (7) m and n are independently selected from 0, 1, 2, 3 and 4; and / or (8) p is selected from 0, 1, 2 and 3.

16. The compound of any one of claims 1-15, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite, prodrug, or pharmaceutically acceptable salt or ester thereof, wherein the compound has the structure shown in formula (I-2) or formula (I-3): in, R 1 R 2 R 3 R 4 And m as defined in any one of claims 1-15.

17. The compound of claim 1, or its stereoisomers, tautomers, polymorphs, solvates, N-oxides, isotopically labeled compounds, or their metabolites, prodrugs, or pharmaceutically acceptable salts or esters, wherein the compound has a structure shown in formula (I-4) or formula (I-5): in, R 1 R 2 R 3 R 4 X 3 X 4 X 6 , m, n as defined in any one of claims 1-16, X 7 X 8 X 9 X 10 Each is independently selected from N and CH, and q is selected from 0 and 1.

18. The compound of any one of claims 1-15, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite, prodrug, or pharmaceutically acceptable salt or ester thereof, wherein, or Selected from:

19. The compound of any one of claims 1-18, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite, prodrug, or pharmaceutically acceptable salt or ester thereof, wherein, The compounds mentioned are selected from:

20. A treatment combination or pharmaceutical combination comprising the compound of any one of claims 1-19, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite or prodrug or pharmaceutically acceptable salt or ester thereof, optionally further comprising one or more other therapeutic agents.

21. A pharmaceutical composition comprising a preventive and / or therapeutically effective amount of any one of claims 1-19, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite or prodrug or pharmaceutically acceptable salt or ester thereof, and one or more pharmaceutically acceptable excipients.

22. The use of any compound of claims 1-19, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite or prodrug or pharmaceutically acceptable salt or ester thereof, or the therapeutic combination or pharmaceutical combination of claim 20, or the pharmaceutical composition of claim 21, in the preparation of a medicament for the prevention and / or treatment of a disease, preferably, wherein the disease is an NRF2 dysregulation-related disease such as a tumor or cancer.

23. The compound of any one of claims 1-19, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite or prodrug or pharmaceutically acceptable salt or ester thereof, or the therapeutic combination or pharmaceutical combination of claim 20, or the pharmaceutical composition of claim 21, for the prevention and / or treatment of a disease, said disease being an NRF2 dysregulation-related disease such as tumors or cancer.

24. A method for preventing and / or treating a disease, the method comprising administering to an individual in need an effective amount of any one of claims 1-19, or a stereoisomer, tautomer, polymorph, solvate, N-oxide, isotopically labeled compound, or a metabolite or prodrug or pharmaceutically acceptable salt or ester thereof, or a treatment combination or pharmaceutical combination of claim 20, or a pharmaceutical composition of claim 21, preferably, the disease being an NRF2 dysregulation-related disease such as a tumor or cancer.

25. A method for preparing the compound according to any one of claims 1-19, comprising the following steps: in, Rings A and R 1 R 2 R 3 R 4 X 1 X 2 m and n are as defined in any one of claims 1-19; LG 1 Indicates the leaving group in a coupling reaction; LG 2 Indicates the leaving group in a coupling reaction; LG 3 Indicates leaving group; PG 1 Indicates an amino protecting group; (1) React compound I-1-1 with compound I-1-1-a to obtain compound I-1-2; (2) React compound I-1-2 to obtain compound I-1-3; (3) Reduce compound I-1-3 to obtain compound I-1-4; (4) React compound I-1-4 with compound I-1-4-a to obtain compound I; Alternatively, it may include the following steps: Among them, rings A and R 1 R 2 R 3 R 4 X 1 X 2 m and n are as defined in any one of claims 1-19; LG 1 Indicates the leaving group in a coupling reaction; LG 3 Indicates leaving group; PG 1 Indicates an amino protecting group; LG 4 Indicates the leaving group in a coupling reaction; (1) Compound I-1-1 and I-1-1-b were subjected to a decarboxylation coupling reaction to obtain compound I-1-5; (2) React compound I-1-5 to obtain compound I-1-4; (3) React compound I-1-4 with compound I-1-4-a to obtain compound I.

26. A method for preparing the compound of claim 16, comprising the following steps: in, R 1 R 2 R 3 R 4 and m as defined in any one of claims 1-15; X represents a halogen atom, including chlorine, bromine and iodine; (1) Compound I-2-1 was subjected to a halogenation reaction to obtain compound I-2-2; (2) Compound I-2-2 and I-2-2-a undergo a condensation reaction to obtain compound I-2-3; (3) Compound I-2-3 undergoes a cyclization reaction to obtain compound I-2-4; (4) React compound I-2-4 to obtain compound I-2-5; (5) React compound I-2-5 with compound I-2-5-a to obtain compound I-2-6; (6) React compound I-2-6 to obtain compound I-2-7; (7) Reduce compound I-2-7 to obtain compound I-2-8; (8) React compound I-2-8 with compound I-2-8-a to obtain compound I-2; Alternatively, it may include the following steps: Among them, R 1 R 2 R 3 R 4 m is as defined in any one of claims 1-15; X represents a halogen atom, including chlorine, bromine, and iodine; LG represents a leaving group; (1) React compound I-3-1 with I-3-1-a to obtain compound I-3-2; (2) React compound I-3-2 to obtain compound I-3-3; (3) React compound I-3-3 with compound I-2-5-a to obtain compound I-3-4; (4) React compound I-3-4 to obtain compound I-3-5; (5) Reduce compound I-3-5 to obtain compound I-3-6; (6) React compound I-3-6 with compound I-2-8-a to obtain compound I-3.

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