Sulfur / oxygen substituted glutarimidylimidoisoindolinone scaffold-based compounds and their applications

Abstract

The present disclosure relates to the technical field of molecular glue decomposers, and in particular to a compound of formula I based on a sulfur / oxygen substituted glutarimidylimide isoindolinone skeleton and its applications. The present disclosure further relates to a compound of formula A and its applications. JPEG2026502207000117.jpg44146

Description

[Technical Field]

[0001] The present disclosure relates to the technical field of molecular glue decomposers, and in particular to compounds based on sulfur / oxygen substituted glutarimidylimidoisoindolinone scaffolds and their applications. [Background technology]

[0002] Phthalimide immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide, have shown remarkable efficacy in the treatment of multiple myeloma and autoimmune diseases. However, it was not until 2010 that their direct binding protein, the E3 ubiquitin ligase cereblon (CRBN), was identified. It was subsequently demonstrated that this class of drug acts as a molecular glue, inducing the interaction between the transcription factors IKZF1 / 3 and CRBN, leading to ubiquitination and degradation. Molecular glue proteolytic drugs have the advantage of a natural mechanism over traditional small molecule inhibitors: whereas the latter act by occupying the functional domain of target proteins and inhibiting their function, proteolytic drugs directly degrade the entire target protein, sometimes resulting in greater efficacy than traditional small molecule inhibitors and enabling them to target "non-druggable" targets. Furthermore, proteolytic drugs do not require high binding strength and require only low catalytic doses to function, thus overcoming the clinical drug resistance problem of traditional small molecule inhibitors. Furthermore, molecular glue degrading drugs generally have small molecular weights and are easy to develop, making their development highly valued. Based on the mechanism of CRBN E3 ubiquitin ligase and molecular glue degradation, a series of compounds have been developed, including the commercially available pomalidomide and Bristol-Myers Squibb (BMS) CC-122, CC-220, CC-90009, CC-99282, and CC-92480, Novartis DKY709, and C4 Therapeutics CFT7455. The degradation substrates of these molecular glues extend from the initially discovered transcription factor IKZF1 / 3 to also include casein kinase 1α (CK1α), zinc finger protein 91 (ZFP91), translation factor GSPT1, etc. By degrading these protein substrates, molecular glues exert pharmacodynamic activities (including, but not limited to, immunomodulation, anti-inflammatory, and anti-tumor effects) for diseases or conditions associated with these protein substrates.Currently, only a very limited number of molecular glue candidate compounds have been discovered, and theoretically, there are a wide variety of pathogenic proteins for which molecular glues can be developed as degradation substrates. Therefore, it is necessary to develop more molecular glues through rationalization and diversification design, decompose and remove more pathogenic proteins, and apply them to the treatment of pathogenic protein-related diseases.

[0003] The present disclosure aims to meet the needs of clinical applications by developing more novel molecular glue decomposers with high efficiency, low toxicity, stable properties, and low cost through rational design based on the phenylglutarimide skeleton. Summary of the Invention [Problem to be solved by the invention]

[0004] The present invention aims to provide compounds based on sulfur / oxygen substituted glutarimidylimidoisoindolinone scaffold and their applications to solve the problems in the prior art. [Means for solving the problem]

[0005] To achieve the above and other related objects, in one aspect, the present disclosure provides a compound of the chemical structure represented by Formula I, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof: [ka] Formula I In Formula I, X is selected from CO or CH2; L1 is selected from S or O; X1 is selected from the group consisting of substituted or unsubstituted straight or branched chain alkylene, or X1 is absent; X2 represents a structure of formula II; [ka] Formula II In Formula II, ring A and ring B are each independently selected from the group consisting of substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, substituted or unsubstituted heterocyclylene, or substituted or unsubstituted cycloalkylene; t represents an integer of 0, 1, or 2; and The symbol # indicates the connection point with X3; X3 is selected from the group consisting of CR1, N, or CO, where R1 is selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, trifluoromethoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched alkyl, or substituted or unsubstituted cycloalkyl; R a1 is selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocyclyl; R a2 is selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocyclyl, or R a2 is absent; and when X3 represents CO, R a2 does not exist and R a1 is not hydrogen or deuterium, and R a2 represents hydrogen or deuterium, X3 represents CR1 or N, and R a1 is not hydrogen or deuterium; R a is selected from the group consisting of deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, halogenated alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R b1 ~R b5are each independently selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, halogenated alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted straight or branched chain alkyl; and n represents an integer of 0, 1, 2, or 3, and when n represents an integer of 2 or 3, each R a are the same or different.

[0006] In another aspect, the present disclosure provides a method for preparing a compound according to the present disclosure, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, comprising the steps of: [ka] In the above steps, (1) E-X3 represents CO, and R a2 represents hydrogen; or (2) E-X3 represents the halogen -CH, MsO-CH, TsO-CH, or NsO-CH; or (3) E-X3 represents CO and R a2 represents hydroxy.

[0007] In another aspect, the present disclosure provides a compound according to the present disclosure or a salt, enantiomer, stereoisomer, polymorph or solvate thereof for use as a medicament.

[0008] In another aspect, the present disclosure provides a pharmaceutical composition comprising a compound according to the present disclosure or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, at least one pharmaceutically acceptable salt, and at least one pharmaceutically acceptable carrier or excipient.

[0009] In another aspect, the present disclosure provides the use of a compound according to the present disclosure or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, or a pharmaceutical composition according to the present disclosure, in the manufacture of a medicament for a disease or condition associated with a cereblon protein.

[0010] In another aspect, the present disclosure provides a method for treating or preventing a cereblon protein-associated disease or condition, comprising administering to a subject a therapeutically effective amount of a compound according to the present disclosure or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, or a pharmaceutical composition according to the present disclosure.

[0011] In another aspect, the present disclosure provides a compound of Formula A according to the present disclosure, having the chemical structure represented as follows: [ka] Formula A In Formula A, X is selected from CO or CH2; L1 is selected from S or O; X1 is selected from the group consisting of substituted or unsubstituted straight or branched chain alkylene, or X1 is absent; X a is a structure of formula A1: [ka] Formula A1 represents In Formula A1, ring C is selected from the group consisting of substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, substituted or unsubstituted heterocyclylene, or substituted or unsubstituted cycloalkylene, and w represents an integer of 0 or 1; and Ring D represents a substituted or unsubstituted nitrogen-containing heterocyclyl; R a is selected from the group consisting of deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, halogenated alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R b1 , R b2 , R b3 , Rb4 and R b5 are each independently selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, halogenated alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted straight or branched chain alkyl; and n represents an integer of 0, 1, 2, or 3, and when n represents an integer of 2 or 3, each R a are the same or different.

[0012] In another aspect, the present disclosure provides a compound of formula A according to the present disclosure or a salt, enantiomer, stereoisomer, polymorph or solvate thereof for use as a medicament.

[0013] In another aspect, the present disclosure provides a pharmaceutical composition comprising a compound of formula A according to the present disclosure or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, at least one pharmaceutically acceptable salt, and at least one pharmaceutically acceptable carrier or excipient.

[0014] In another aspect, the present disclosure provides the use of a compound of formula A according to the present disclosure, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, or a pharmaceutical composition according to the present disclosure, in the manufacture of a medicament for a cereblon protein-related disease or condition.

[0015] In another aspect, the present disclosure provides a method for treating or preventing a cereblon protein-associated disease or condition, comprising administering to a subject a therapeutically effective amount of a compound of formula A according to the present disclosure, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, or a pharmaceutical composition according to the present disclosure. [Effects of the Invention]

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows: The compounds provided in the present invention have a sulfur / oxygen-substituted glutarimidylimidoisoindolinone skeleton. Based on this sulfur / oxygen-substituted glutarimidylimidoisoindolinone skeleton, through rational design, more novel compounds with high efficiency, low toxicity, stable properties and low cost can be used as molecular glue to produce immunomodulatory drugs, anti-inflammatory drugs and antitumor drugs, thereby meeting the needs of clinical application. [Brief explanation of the drawings]

[0017] [Figure 1] 1 shows the results of Western blotting of the compound according to the present invention, which can efficiently degrade substrate proteins such as Wee1, IKZF1, IKZF2, IKZF3, GSPT1, and CK1α proteins in human peripheral blood mononuclear cells (hPBMCs). DETAILED DESCRIPTION OF THE INVENTION

[0018] As a result of extensive and intensive research, the present inventors have provided a compound based on a sulfur / oxygen-substituted glutarimidylimidoisoindolinone skeleton that has a novel structure as a molecular glue, is highly efficient, has low toxicity, has stable properties, and is inexpensive, and can be used in the manufacture of drugs for treating or preventing cereblon protein-related diseases or conditions. Based on this, the present invention has been completed.

[0019] Definition of Terms

[0020] Unless otherwise specified, the following terms, phrases and symbols used herein generally have the following meanings:

[0021] Generally, the nomenclature used herein (e.g., IUPAC nomenclature) and the laboratory programs described below (including those used in cell culture, organic chemistry, analytical chemistry, and pharmacology) are those well known and commonly used in the art. Unless otherwise defined, in accordance with the context of the present disclosure set forth herein, all scientific and technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Additionally, in the claims and / or specification, when the terms "a" and "an" are used in conjunction with the term "comprise" or a noun, the meaning may be "one," but is also consistent with the meanings of "one or more," "at least one," and "one or more than one." Similarly, the terms "another" or "another" can denote at least a second or more.

[0022] When embodiments are described herein using the terms "comprising" or "having," it should be understood that other embodiments similar to the statements "consisting of" and / or "consisting essentially of" are also provided.

[0023] Herein, bonds broken by wavy lines indicate the point of attachment of the depicted group to the rest of the molecule. For example, in the group L3 depicted below: [ka] represents the connection between said group and group L2 in compounds of formula I.

[0024] Also included within the scope of the present disclosure are salts or pharmaceutically acceptable salts, enantiomers, stereoisomers, solvates, and polymorphs of the compounds of Formula I according to the present disclosure.

[0025] As used herein, the term "enantiomer" is to be understood as meaning that when in this application a particular compound (or generic structure) is designated as the (R)- or (S)-enantiomer / has the absolute (R)- or (S)-configuration, said designation refers to the corresponding compound (or generic structure) in enriched, in particular essentially pure, enantiomer form.

[0026] As used herein, "stereoisomers" refer to compounds that have the same chemical constitution but differ in the way the atoms or groups are arranged in space. Stereoisomers include enantiomers, non-enantiomers, conformational isomers (rotational isomers), geometric isomers (cis / trans) isomers, atropisomers, etc.

[0027] As used herein, the term "polymorph" refers to a solid crystalline form of a compound disclosed herein or a complex thereof. Different polymorphs of the same compound may exhibit different physical, chemical, and / or spectroscopic properties. Differences in physical properties include, but are not limited to, stability (e.g., thermal or light stability), compressibility and density (important in formulation and product manufacturing), and dissolution rate (which may affect bioavailability). Differences in stability can result in changes in chemical reactivity (e.g., differential oxidation, such that a dosage form consisting of one polymorph discolors more quickly than one consisting of another polymorph), changes in mechanical properties (e.g., tablets disintegrate during storage as a kinetically favored polymorph converts to a thermodynamically more stable polymorph), or both (e.g., tablets of one polymorph are more susceptible to fracture at high humidity). The different physical properties of polymorphs can affect their processing. For example, one polymorph may form more solvates than another, may be more difficult to filter or wash than another polymorph, for example, due to its shape or particle size distribution.

[0028] As used herein, the term "salts or pharmaceutically acceptable salts" refers to non-toxic inorganic or organic acid and / or base addition salts in the present application. Examples include sulfate, hydrohalide (including hydrochloride and hydrobromide), maleate, sulfonate, citrate / citrate, lactate, lactobionate, L-tartrate, fumarate, L-malate, L-lactate, α-ketoglutarate, hippurate, D-glucuronate, D-gluconate, α-D-gluceptate, glycolate, mucate, L-ascorbate, orotate, picrate, glycinate, alanine, arginine, cinnamate, laurate, pamoate, sebacate, benzenesulfonate, methanesulfonate, ethanesulfonate, ethanedisulfonate, formate, acetate, 2,2-dichloroacetate, trimethylacetate, propionate, pentanoate, palmitate, triphenylacetate, and 2-ethylsuccinate. , iodate, nicotinate, L-pyroglutamate, L-proline salt, ferulate, 2-hydroxyethanesulfonate, nitrate, gentisate, cholate, salicylate, terephthalate, glutarate, adipate, stearate, oleate, undecenoate, camphorate, camphorsulfonate, dodecylbenzenesulfonate, phosphate, thiocyanate, dihydrogen phosphate, pyrophosphate, metaphosphate, oxalate, carbonate, malonate, benzoate, mandelate, succinate, pyruvate, p-chlorobenzenesulfonate, 1,5-naphthalenedisulfonate, 3-hydroxy-2-naphthoate, 1-hydroxy-2-naphthoate, 2-naphthalenesulfonate, hydroxyacetate, or p-toluenesulfonate.

[0029] As used herein, the term "solvate" refers to a compound of the present disclosure or a pharmaceutically acceptable salt thereof that contains a stoichiometric or non-stoichiometric solvent bound by non-covalent intermolecular forces. Preferred solvents are volatile, non-toxic, and can be administered to humans in very small dosages. Examples of solvents include, but are not limited to, water, isopropanol, ethanol, methanol, DMSO, ethyl acrylate, acetic acid, and ethanolamine. The term "hydrate" refers to a complex in which the solvent molecule is water.

[0030] As used herein, the term "optionally substituted with" may be used interchangeably with "substituted or unsubstituted." The term "substituted" generally refers to one or more hydrogens in the referenced structure being replaced with the same or different specified substituents. For example, the substituent may be optionally selected from the group consisting of deuterium, halogen, cyano, nitro, hydroxy, mercapto, carbonyl, ester, imido, amino, phosphine oxide, alkoxy, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio, arylthio, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, deuterated alkyl, alkyl halide, amino-substituted alkylene, alkyl-NHC(O)-, alkyl-C(O)NH-, cycloalkyl, deuterated cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino, heteroaryl, heterocyclyl, acenaphthenyl, and oxo; or the substituent may be a substituent formed by linking two or more of the substituents exemplified above. For example, "a substituent to which two or more substituents in the above-exemplified substituents are linked" may include biaryl (for example, biphenyl) and biheteroaryl (for example, bipyridyl).

[0031] As used herein, the term "substituted or unsubstituted amino" may be represented by the chemical formula NY1Y2, where Y1 and Y2 are each hydrogen, deuterium, alkenyl, alkyl (e.g., C1-C3 alkyl), cycloalkyl (e.g., C 3-20 cycloalkyl), heterocyclyl (e.g., 4- to 20-membered heterocyclyl), aryl (e.g., C 6-20 aryl) or heteroaryl (e.g., 5- to 20-membered heteroaryl), where examples of substituted or unsubstituted amino include, but are not limited to, amino, N-methylamino, N-ethylamino, N-phenylamino, N,N-dimethylamino, N,N-diethylamino, etc.

[0032] As used herein, the term "substituted or unsubstituted silyl" refers to SiY a Y b Y c and the above Y a , Y b and Y c are each hydrogen, deuterium, halogen, alkoxy, halogenated alkoxy, alkenyl, alkyl (e.g., C1-C3 alkyl), cycloalkyl (e.g., C 3-20 cycloalkyl), heterocyclyl (e.g., 4- to 20-membered heterocyclyl), aryl (e.g., C 6-20 aryl) or heteroaryl (for example, 5- to 20-membered heteroaryl). Specific examples of the substituted or unsubstituted silyl include, but are not limited to, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, vinyldimethylsilyl, propyldimethylsilyl, triphenylsilyl, diphenylsilyl, and phenylsilyl.

[0033] As used herein, the term "substituted or unsubstituted boryl" refers to a BY d Y e and the above Y d and Y e are hydrogen, deuterium, alkoxy, halogenated alkoxy, alkenyl, alkyl (e.g., C1-C3 alkyl), cycloalkyl (e.g., C 3-20cycloalkyl), heterocyclyl (e.g., 4- to 20-membered heterocyclyl), aryl (e.g., C 6-20 aryl) or heteroaryl (e.g., 5- to 20-membered heteroaryl). Exemplary substituted or unsubstituted boryls include, but are not limited to, trimethylboryl, triethylboryl, tert-butyldimethylboryl, triphenylboryl, phenylboryl, and the like.

[0034] As used herein, the term "is absent," alone or in combination, means that the referenced group is a connecting linker, and that the two groups adjacent to that group are directly connected. For example, the term "X is absent" means that X is a connecting linker. In other words, when X is absent, group L in a compound of formula I is directly connected to group X. Alternatively, for example, "When X represents CO, then R a2 does not exist and R a1 is not hydrogen or deuterium" refers to the group of the compound of formula I. [ka] but [ka] It means to represent.

[0035] As used herein, the term "aryl," alone or in combination, refers to a monovalent aromatic hydrocarbon group (e.g., C5-C6) containing 5 to 30 carbon atoms and optionally containing one or more fused rings. 30 , C5-C 25 , C5-C 20 , C5-C 15"Aryl" refers to a monocyclic aryl or a polycyclic aryl. In some embodiments, monocyclic aryl includes, but is not limited to, phenyl, biphenyl, terphenyl, quaterphenyl, quinquephenyl, etc. Polycyclic aryl includes, but is not limited to, naphthyl, anthryl, phenanthryl, pyrenyl, perylenyl, fluorenyl, etc. Fluorenyl may be substituted, for example, 9,9'-dimethylfluorenyl, 9,9'-diphenylfluorenyl, etc. Two substituents may also be bonded to form a spiro ring structure, for example, 9,9'-spirobifluorenyl, etc. In the present disclosure, the "aryl" refers to an optionally substituted aryl. Substituted aryl refers to an aryl substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent (e.g., mono-, di-, or tri-substituted aryl), where the substituent is optionally substituted, for example, with a deuterated C1-C6 alkyl, deuterated C 3-6 The alkyl group is selected from the group consisting of cycloalkyl, deuterium, hydroxy, amino, mercapto, halogen, cyano, nitro, carbonyl, an ester group, an imide group, a phosphine oxide group, trifluoromethoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, alkyl, cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, heterocyclyl, acenaphthenyl, and any combination thereof.

[0036] As used herein, the term "arylene," alone or in combination, refers to a divalent aromatic hydrocarbon group containing 5 to 30 carbon atoms and optionally containing one or more fused rings. For example, C5-C 30 , C5-C 25 , C5-C 20 , C5-C 15 Arylene, etc. C5-C 30The arylene may be a monocyclic arylene or a polycyclic arylene. Monocyclic arylenes include, but are not limited to, phenylene, biphenylene, terphenylene, quaterphenylene, quinquephenylene, etc. Polycyclic aryls include, but are not limited to, naphthylene, anthrylene, phenanthrylene, pyrenylene, perylenylene, fluorenylene, etc. The fluorenylene may be substituted, for example, 9,9'-dimethylfluorenylene, 9,9'-diphenylfluorenylene, etc. Furthermore, two substituents may be bonded to each other to form a spiro ring structure, for example, 9,9'-spirobifluorenylene, etc. In the present disclosure, the "arylene" is an optionally substituted arylene. Substituted arylene refers to an arylene (e.g., an arylene that is mono-, di-, or tri-substituted with substituents) that is substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent, where the substituents are optionally selected from, for example, deuterated C1-C6 alkyl, deuterated C3-C6 cycloalkyl, deuterium, hydroxy, amino, mercapto, halogen, cyano, nitro, carbonyl, an ester group, an imide group, a phosphine oxide group, trifluoromethoxy, deuterated C1-C6 It is selected from the group consisting of alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, alkyl, cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, heterocyclyl, acenaphthenyl, and any combination thereof.

[0037] As used herein, the term "heteroaryl," alone or in combination, refers to a 5-30-membered (optionally 5-20-membered, 5-15-membered, 5-12-membered, 5-11-membered, 5-10-membered, 5-9-membered, 5-8-membered, 5-7-membered, 5-6-membered, 6-15-membered, or 6-9-membered) monocyclic, bicyclic, or polycyclic monovalent heteroaryl having at least one aromatic ring containing one or more (e.g., 1 to 6, or 1 to 5, or 1 to 4, or 1 to 3) heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. Bicyclic or polycyclic heteroaryl includes bicyclic, tricyclic, or tetracyclic heteroaryl, in which one ring is an aromatic ring containing one or more heteroatoms independently selected from the group consisting of O, S, and N, and the other rings may be saturated, partially unsaturated, or aromatic, and may be carbocyclic or contain one or more heteroatoms independently selected from the group consisting of O, S, and N.Heteroaryl includes furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazolyl, tetrazolyl, pyranyl, thiopyranyl, thiazinyl, triazinyl, tetrazinyl, indolyl, indolinyl, isoindolyl, isoindolinyl, benzofuranyl, isobenzofuranyl, benzothienyl, indazolyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, cinnolinyl, naphthyridinyl, acridinyl, xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolizinyl, phthalazinyl, pyrazolopyridinyl, Examples of heteroaryl include, but are not limited to, pyrazolopyrimidinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, pyrrolopyridinyl, pyrrolothiazolyl, imidazothiazolyl, pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl. The heteroaryl may be substituted or unsubstituted.Substituted heteroaryl refers to heteroaryl substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent, wherein the substituent is optionally selected from the group consisting of C-C alkyl, C-C cycloalkyl, hydroxy, amino, mercapto, halogen, deuterium, nitro, carbonyl, an ester group, an imido group, a phosphine oxide group, trifluoromethoxy, C-C alkoxy, C-C alkylamino, halogenated C-C alkyl, amino-substituted C-C alkylene, C-C alkyl-NHC(O)—, C-C alkyl-C(O)NH—, cyano, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, heterocyclyl, acenaphthenyl, or any combination thereof.

[0038] As used herein, the term "heteroarylene," whether used alone or in combination, refers to a 5- to 30-membered (optionally 5-20-membered, 5- to 15-membered, 5- to 12-membered, 5- to 11-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7-membered, 5- to 6-membered, 6- to 15-membered, or 6- to 9-membered) monocyclic, bicyclic, or polycyclic divalent aromatic ring group containing one or more (e.g., 1 to 6, 1 to 5, 1 to 4, or 1 to 3) heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur. Bicyclic or polycyclic heteroarylene includes bicyclic, tricyclic, or tetracyclic heteroarylene, in which one ring is an aromatic ring containing one or more heteroatoms independently selected from the group consisting of O, S, and N, and the other rings may be saturated, partially unsaturated, or aromatic, and may be carbocyclic or contain one or more heteroatoms independently selected from the group consisting of O, S, and N.Heteroarylene includes furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, tetrazolylene, pyranylene, thiopyranylene, thiazinylene, triazinylene, tetrazinylene, and indolylene. , indolinylene, isoindolinylene, isoindolinylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, quinolinylene, isoquinolinylene, quinazolinylene, quinoxalinylene, cinnolinylene, naphthyridinylene, acridinylene, xanthenylene, phenanthridinylene, diazanaphthylene, triazaindenylene, indolizinylene, phthalazinylene, pyrazolo Pyridylene, pyrazolopyrimidinylene, pyridopyrimidinylene, pyridopyrazinylene, pyrazinopyrazinylene, benzothiazolylene, benzoxazolylene, benzimidazolylene, dibenzothienylene, dibenzofuranylene, carbazolylene, benzocarbazolylene, dibenzocarbazolylene, indolocarbazolylene, indenocarbazolylene, phenazinylene, imidazopyridinylene, phenanthridylene Examples of heteroarylene include, but are not limited to, phenylene, phenanthrolinylene, phenothiazinylene, imidazopyridinylene, imidazophenanthridinylene, pyrrolopyridinylene, pyrrolothiazolylene, imidazothiazolylene, benzimidazoquinazolinylene, benzimidazophenanthridinylene, pyrenylene, dinaphthofuranylene, naphthobenzofuranylene, dinaphthothienylene, naphthobenzothienylene, etc. The heteroarylene may be unsubstituted or substituted.Substituted heteroarylene refers to a heteroarylene substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent, wherein the substituent is optionally selected from the group consisting of C-C alkyl, C-C cycloalkyl, hydroxy, amino, mercapto, halogen, deuterium, nitro, carbonyl, an ester group, an imido group, a phosphine oxide group, trifluoromethoxy, C-C alkoxy, C-C alkylamino, halogenated C-C alkyl, amino-substituted C-C alkylene, C-C alkyl-NHC(O)—, C-C alkyl-C(O)NH—, cyano, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, heterocyclyl, acenaphthenyl, or any combination thereof.

[0039] As used herein, the term "heterocyclyl," whether used alone or in combination, refers to a monocyclic, bicyclic, tricyclic, or polycyclic saturated or partially unsaturated cycloalkyl (i.e., having one or more double bonds but not completely conjugated) containing one or more (e.g., including 1 to 5, or 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from the group consisting of sulfur, oxygen, and nitrogen, and the number of carbon atoms is not particularly limited. For example, it refers to a 4- to 30-membered heterocyclyl, a 4- to 25-membered heterocyclyl, a 4- to 20-membered heterocyclyl, a 4- to 15-membered heterocyclyl, a 4- to 10-membered heterocyclyl, a 10- to 15-membered heterocyclyl, a 7- to 15-membered heterocyclyl, or a 5- to 15-membered heterocyclyl. Bicyclic, tricyclic, and polycyclic heterocyclyls include bridged heterocyclyls (e.g., 5-20-membered, 5-15-membered, 5-11-membered, 5-10-membered, 7-20-membered, 7-15-membered, and 7-9-membered bridged heterocyclyls), fused heterocyclyls (e.g., 5-20-membered, 5-15-membered, 5-11-membered, 5-10-membered, 7-20-membered, 7-15-membered, and 7-9-membered fused heterocyclyls), and spiroheterocyclyls (e.g., 5-20-membered, 5-15-membered, 5-11-membered, 5-10-membered, 7-20-membered, 7-15-membered, and 7-9-membered spiroheterocyclyls). For example, heterocyclyls contain 1 to 3 heteroatoms, or 1 to 2 heteroatoms, or 1 heteroatom, etc. Each heteroatom is independently selected from the group consisting of O, N, S, and the like.Further examples of the heterocyclyl include azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, dioxacyclohexenyl, azacyclohexyl, and the like. butanyl, azacyclooctyl, diazacycloheptanyl (e.g., 1,4-diazacycloheptanyl, 4,5-diazacycloheptanyl, or 1,3-diazacycloheptanyl), diazacyclooctyl, azabicyclohexyl (e.g., 3-azabicyclo[3.1.0]hexyl), azabicycloheptanyl (e.g., 3-azabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.2.0] butanyl, 6-azabicyclo[3.1.1]heptan-3-yl, etc.), diazabicycloheptanyl (e.g., 2,5-diazabicyclo[2.2.1]heptan-2-yl, 3,6-diazabicyclo[3.1.1]heptan-3-yl), azabicyclooctyl (e.g., cis-7-azabicyclo[3.3.0]octanyl, 3-azabicyclo[3.2.1]octan-8-yl, etc.), diazabicyclooctyl and the like. Examples of heterocyclic groups include, but are not limited to, aryl (e.g., 3,8-diazabicyclo[3.2.1]octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-3-yl, 2,5-diazabicyclo[2.2.2]octan-2-yl), spiroheterocyclyl (e.g., 5- to 15-membered or 7- to 15-membered spiroheterocyclyl, 7-azaspiro[3.5]nonanyl, 3-azaspiro[5,5]undecanyl, and the like).The heterocyclyl may be unsubstituted or substituted (e.g., mono-, di-, tri-, or poly-substituted) as clearly defined, where the substituents are optionally selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, carbonyl, ester, imido, phosphine oxide, trifluoromethoxy, oxo, optionally deuterated 1-C alkyl, halogenated C-C alkyl, optionally deuterated 3-C cycloalkyl, optionally deuterated 1-C alkoxy, C-C alkyl-NH—, NH—C-C alkylene, C-C alkyl-NHC(O)—, C-C alkyl-C(O)NH—, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino, heteroaryl, heterocyclyl, acenaphthenyl, and any combination thereof.

[0040] As used herein, the term "nitrogen-containing heterocyclyl," used alone or in combination, refers to a 4- to 30-membered (e.g., 4-20-membered, 4-15-membered, 4-14-membered, 4-13-membered, 4-12-membered, 4-11-membered, 4-10-membered, 4-9-membered, 4-8-membered, 4-7-membered, 4-6-membered, 4-5-membered, 4-9-membered, 5-20-membered, 5-15-membered, 7-20-membered, or 7-15-membered) monocyclic, bicyclic, tricyclic, or polycyclic saturated and partially unsaturated (e.g., containing one or more double bonds but not completely conjugated) cyclic hydrocarbon group containing one nitrogen atom and optionally containing one or more (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from the group consisting of sulfur, oxygen, and nitrogen. Examples of the term "nitrogen-containing heterocyclyl" include, but are not limited to, nitrogen-containing monocyclic heterocyclyl (e.g., 4- to 30-membered or 4- to 20-membered nitrogen-containing monocyclic heterocyclyl), nitrogen-containing bridged heterocyclyl (e.g., 5- to 20-membered nitrogen-containing bridged heterocyclyl or 7- to 20-membered nitrogen-containing bridged heterocyclyl), nitrogen-containing fused heterocyclyl (e.g., 5- to 20-membered or 7- to 20-membered nitrogen-containing fused heterocyclyl), and nitrogen-containing spiroheterocyclyl (e.g., 5- to 20-membered or 7- to 20-membered nitrogen-containing spiroheterocyclyl). Representative examples of nitrogen-containing monocyclic heterocyclyls include, but are not limited to, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, azacycloheptanyl, azacyclooctyl, diazacycloheptanyl (e.g., 1,4-diazacycloheptan-1-yl), and diazacyclooctyl.Examples of nitrogen-containing bridged heterocyclyls, nitrogen-containing fused heterocyclyls, and nitrogen-containing spiroheterocyclyls include, but are not limited to, 6-azabicyclo[3.1.1]heptan-3-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl, 3,6-diazabicyclo[3.1.1]heptan-3-yl, 3-azabicyclo[3.2.1]octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-8-yl, 3,8-diazabicyclo[3.2.1]octan-3-yl, 2,5-diazabicyclo[2.2.2]octan-2-yl, and azaspirocycloalkyl (e.g., 5- to 20-membered azaspirocycloalkyl, such as 3-azaspiro[5.5]undecan-3-yl). The nitrogen-containing heterocyclyl may be unsubstituted or substituted (e.g., mono-, di-, tri-, or poly-substituted) as clearly defined, where the substituents are optionally selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, carbonyl, ester group, imido group, phosphine oxide group, trifluoromethoxy, oxo group, optionally deuterated 1-C6 alkyl, halogenated C1-C6 alkyl, optionally deuterated 3-C6 cycloalkyl, optionally deuterated 1-C6 alkoxy, C1-C4 alkyl-NH-, NH2-C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino group, alkyl, cycloalkyl, heteroaryl, heterocyclyl, acenaphthenyl, and any combination thereof.

[0041] As used herein, the term "heterocyclylene," whether used alone or in combination, refers to a monocyclic, bicyclic, tricyclic, or polycyclic saturated or partially unsaturated (i.e., having one or more double bonds but not completely conjugated) divalent cycloalkyl group containing one or more (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1) heteroatoms independently selected from the group consisting of sulfur, oxygen, and nitrogen, and the number of carbon atoms is not particularly limited. Examples include 4- to 30-membered heterocyclylene, 4- to 25-membered heterocyclylene, 4- to 20-membered heterocyclylene, 4- to 15-membered heterocyclylene, 4- to 10-membered heterocyclylene, 10- to 15-membered heterocyclylene, 7- to 15-membered heterocyclylene, and 5- to 15-membered heterocyclylene. Bicyclic, tricyclic, and polycyclic heterocyclylenes include bridged heterocyclylenes (e.g., 5-20-membered, 5-15-membered, 5-11-membered, 5-10-membered, 7-20-membered, 7-15-membered, and 7-9-membered bridged heterocyclylenes), fused heterocyclylenes (e.g., 5-20-membered, 5-15-membered, 5-11-membered, 5-10-membered, 7-20-membered, 7-15-membered, and 7-9-membered fused heterocyclylenes), and spiroheterocyclylenes (e.g., 5-20-membered, 5-15-membered, 5-11-membered, 5-10-membered, 7-20-membered, 7-15-membered, and 7-9-membered spiroheterocyclylenes). For example, heterocyclylenes contain 1 to 3 heteroatoms, or 1 to 2 heteroatoms, or 1 heteroatom, etc. Each heteroatom is independently selected from the group consisting of O, N, S, and the like.Further examples of heterocyclylene include azetidinylene, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, dihydropyranylene, tetrahydrothienylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, dioxacyclohexylene, dioxacyclohexenylene, azacycloheptanylene, azacyclooctylene, or diazacycloheptanylene (e.g., 1,4-diazacycloheptanylene, 4,5-diazacycloheptanylene, or 1,3-diazacycloheptanylene), diazacyclooctylene, azabicyclohexylene (e.g., 3-azabicyclohexylene, 4-azabicyclohexylene, 5-azabicyclohexylene, 6-azabicyclohexylene, 7-azabicyclohexylene, 8-azabicyclohexylene, 9-azabicyclohexylene, 10-azabicyclohexylene, 11-azabicyclohexylene, 12-azabicyclohexylene, 13-azabicyclohexylene, 14-azabicyclohexylene, 15-azabicyclohexylene, 16-azabicyclohexylene, 17-azabicyclohexylene, 18-azabicyclohexylene, 19-azabicyclohexylene, 20-azabicyclohexylene, 21-azabicyclohexylene, 22-azabicyclohexylene, 23-azabicyclohexylene, 24-azabicyclohexylene, 25-azabicyclohexylene, 26-azabicyclohexylene, 27-azabicyclohexylene, 28-azabicyclohexylene, 29-azabicyclohexylene, 30-azabicyclohexylene, 31-azabicyclohexylene, 32-azabicyclohexylene, 33 cis-7-azabicyclo[3.3.0]octanylene, 3-azabicyclo[3.2.1]octanylene, etc.), azabicycloheptanylene (e.g., 3-azabicyclo[3.1.1]heptanylene, 3-azabicyclo[3.2.0]heptanylene, 6-azabicyclo[3.1.1]heptanylene, etc.), azabicyclooctylene (e.g., cis-7-azabicyclo[3.3.0]octanylene, 3-azabicyclo[3.2.1]octanylene, etc.) , diazabicyclooctylene (e.g., 3,8-diazabicyclo[3.2.1]octanylene, 2,5-diazabicyclo[2.2.2]octanylene), or spiroheterocyclylene (e.g., 5- to 15-membered or 7- to 15-membered spiroheterocyclylene, 7-azaspiro[3.5]nonanylene, 3-azaspiro[5,5]undecanylene, etc.).The heterocyclylene may be unsubstituted or substituted (e.g., mono-, di-, tri-, or poly-substituted) as clearly defined, where the substituents are optionally selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, carbonyl, ester, imido, phosphine oxide, trifluoromethoxy, oxo, optionally deuterated 1-C alkyl, halogenated C-C alkyl, optionally deuterated 3-C cycloalkyl, optionally deuterated 1-C alkoxy, C-C alkyl-NH—, NH—C-C alkylene, C-C alkyl-NHC(O)—, C-C alkyl-C(O)NH—, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino, alkyl, cycloalkyl, heteroaryl, heterocyclyl, acenaphthenyl, and any combination thereof.

[0042] The term "cycloalkyl," as used herein, alone or in combination, refers to a saturated or partially unsaturated (i.e., having one or more double bonds, but not fully conjugated) mono-, bi-, or polycyclic hydrocarbon group, and in some embodiments, has from 3 to 20 carbon atoms (i.e., C 3-20 cycloalkyl), or 3 to 15 carbon atoms (i.e., C 3-15 cycloalkyl), 3 to 12 carbon atoms (i.e., C 3-12 cycloalkyl), or 3 to 11 carbon atoms (i.e., C 3-11 cycloalkyl), or 3 to 10 carbon atoms (i.e., C 3-10 cycloalkyl), or 3 to 8 carbon atoms (i.e., C 3-8 cycloalkyl), or 3 to 7 carbon atoms (i.e., C 3-7 cycloalkyl), or 3 to 6 carbon atoms (i.e., C 3-6 cycloalkyl), or 4 to 20 carbon atoms (i.e., C 4-20 cycloalkyl), or 4 to 15 carbon atoms (i.e., C 4-15 cycloalkyl), or 5 to 20 carbon atoms (i.e., C5-20 cycloalkyl), or 5 to 15 carbon atoms (i.e., C 5-15 The term "C3-C cycloalkyl" 20 "Cycloalkyl" refers to a saturated or partially unsaturated (i.e., having one or more double bonds but not completely conjugated) mono-, bi-, or polycyclic hydrocarbon group having 3 to 20 carbon atoms. The term "cycloalkyl" includes mono-, bi-, tri-, and polycyclic cycloalkyls. Bi-, tri-, and polycyclic cycloalkyls include bridged cycloalkyls (e.g., C 5-20 Bridged cycloalkyl, C 5-15 Bridged cycloalkyl, C 7-20 Bridged cycloalkyl, C 7-15 Bridged cycloalkyl, C 7-11 bridged cycloalkyl), fused cycloalkyl (e.g., C 5-20 Fused cycloalkyl, C 5-15 Fused cycloalkyl, C 7-20 Fused cycloalkyl, C 7-15 Fused cycloalkyl, C 7-11 fused cycloalkyl) and spirocycloalkyl (e.g., C 5-20 Spirocycloalkyl, C 5-15 Spirocycloalkyl, C 7-20 Spirocycloalkyl, C 7-15 Spirocycloalkyl, C 7-11 Representative examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C 5-20Spirocycloalkyl (e.g., spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), adamantanyl, noradamantanyl, bornyl, norbornyl (IUPAC systematic name: biscyclo[2.2.1]heptyl), and cubanyl. In the present disclosure, the "cycloalkyl" is optionally substituted, and the substituents are preferably trifluoromethyl, mercapto, hydroxy, amino, halogen, cyano, C1-C3 alkoxy, trifluoromethyl, heterocyclyl, deuterium, nitro, carbonyl, ester group, imido group, amino, phosphine oxide group, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl (e.g., C1-C3 alkyl), and one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents selected from the group consisting of alkyl, deuterated alkyl, amino-substituted alkylene, alkyl-NHC(O)—, alkyl-C(O)NH—, cycloalkyl, deuterated cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, acenaphthenyl, oxo group, or any combination thereof.

[0043] The term "cycloalkylene," as used herein, alone or in combination, refers to a saturated and partially unsaturated (e.g., containing one or more double bonds, but not fully conjugated) monocyclic, bicyclic, or polycyclic hydrocarbon divalent radical, and in some embodiments, contains 3 to 20 carbon atoms (i.e., C 3-20 cycloalkylene), or 3 to 15 carbon atoms (i.e., C 3-15 cycloalkylene), 3 to 12 carbon atoms (i.e., C 3-12 cycloalkylene), or 3 to 11 carbon atoms (i.e., C 3-11 cycloalkylene), or 3 to 10 carbon atoms (i.e., C 3-10cycloalkylene), or 3 to 8 carbon atoms (i.e., C 3-8 cycloalkylene), or 3 to 7 carbon atoms (i.e., C 3-7 cycloalkylene), or 3 to 6 carbon atoms (i.e., C 3-6 cycloalkylene), or 4 to 20 carbon atoms (i.e., C 4-20 cycloalkylene), or 4 to 15 carbon atoms (i.e., C 4-15 cycloalkylene), or 5 to 20 carbon atoms (i.e., C 5-20 cycloalkylene), or 5 to 15 carbon atoms (i.e., C 5-15 The term "C3-C 20 "Cycloalkylene" refers to a divalent group of saturated and partially unsaturated (e.g., containing one or more double bonds, but not fully conjugated) mono-, bi-, or polycyclic hydrocarbon rings having 3 to 20 carbon atoms. The term "cycloalkylene" includes mono-, bi-, tri-, and polycyclic cycloalkylenes. Bi-, tri-, and polycyclic cycloalkylenes include bridged cycloalkylenes (e.g., C 5-20 Bridged cycloalkylene, C 5-15 Bridged cycloalkylene, C 7-20 Bridged cycloalkylene, C 7-15 Bridged cycloalkylene, C 7-11 bridged cycloalkylene), fused cycloalkylene (e.g., C 5-20 Fused cycloalkylene, C 5-15 Fused cycloalkylene, C 7-20 Fused cycloalkylene, C 7-15 Fused cycloalkylene, C 7-11 fused cycloalkylenes) and spirocycloalkylenes (e.g., C 5-20 Spirocycloalkylene, C 5-15 Spirocycloalkylene, C 7-20 Spirocycloalkylene, C 7-15 Spirocycloalkylene, C 7-11Representative examples of cycloalkylene include cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decalinylene, octahydrocyclopentalenylene, octahydro-1H-indenylene, spirocycloalkylene (e.g., C 5-20 Spirocycloalkylenes include, but are not limited to, spiro[3.3]heptanylene, spiro[2.5]octanylene, spiro[3.5]nonylene, spiro[4.4]nonylene, spiro[4.5]decylene, or spiro[5.5]undecylene), adamantanylene, noradamantanylene, bornylene, norbornylene (IUPAC systematic name biscyclo[2.2.1]heptylene), and cubanylene. By definition, cycloalkylene groups can be unsubstituted or substituted. In the present disclosure, the substituent of the substituted "cycloalkylene" is preferably trifluoromethyl, mercapto, hydroxy, amino, halogen, cyano, C1-C3 alkoxy, trifluoromethyl, heterocyclyl, deuterium, nitro, carbonyl, ester group, imide group, phosphine oxide group, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl (e.g., C1-C3 alkyl), deuterium, and one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents selected from the group consisting of deuterated alkyl, amino-substituted alkylene, alkyl-NHC(O)—, alkyl-C(O)NH—, cycloalkyl, deuterated cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, acenaphthenyl, oxo group, or any combination thereof.

[0044] As used herein, the term "alkyl" used alone or in combination may refer to straight-chain or branched-chain alkyl, and the number of carbon atoms is not particularly limited. For example, C1-C 30, C1-C 25 , C1-C 20 , C1-C 15 , C1-C 10 , C1-C5, etc. By way of example, alkyl includes, but is not limited to, methyl, ethyl, propyl, normal propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methyl-butyl, 1-ethyl-butyl, pentyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 4-methyl-2-pentyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl, n-heptyl, 1-methylhexyl, cyclopentylmethyl, cyclohexylmethyl, octyl, n-octyl, tert-octyl, 1-methylheptyl, 2-ethylhexyl, 2-propylpentyl, n-nonyl, 2,2-dimethylheptyl, 1-ethyl-propyl, 1,1-dimethyl-propyl, isohexyl, 4-methylhexyl, 5-methylhexyl, etc. In the present disclosure, the "alkyl" is optionally substituted, and the substituent is optionally one or more substituents selected from the group consisting of D (i.e., deuterium), halogen, hydroxy, cyano, C1-C3 alkoxy, trifluoromethyl, heterocyclyl (e.g., 4- to 8-membered heterocyclyl), nitro, mercapto, carbonyl, ester group, imido group, amino, phosphine oxide group, alkoxy, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl (e.g., C1-C3 alkyl), deuterated alkyl, alkyl halide, amino-substituted alkylene, alkyl-NHC(O)-, alkyl-C(O)NH-, cycloalkyl, deuterated cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, acenaphthenyl, oxo group, or any combination thereof.

[0045] As used herein, the term "alkylene" used alone or in combination may refer to a linear or branched divalent saturated hydrocarbon group consisting of carbon and hydrogen atoms, and the number of carbon atoms is not particularly limited. For example, C1-C 30 , C1-C 25 , C1-C 20 , C1-C 15 , C1-C 10, C1-C5 alkylene, etc. By way of example, alkylene can be methylene, ethylene, propylene, isopropylene, butylene, n-butylene, isobutylene, tert-butylene, sec-butylene, 1-methyl-butylene, 1-ethyl-butylene, pentylene, n-pentylene, isopentylene, neopentylene, and tert-pentylene, hexylene, n-hexylene, 1-methylpentylene, 2-methylpentylene, 4-methyl-2-pentylene, 3,3-dimethylbutylene, 2-ethyl ... Including, but not limited to, butylene, heptylene, n-heptylene, 1-methylhexylene, cyclopentylmethylene, cyclohexylmethylene, octylene, n-octylene, tert-octylene, 1-methylheptylene, 2-ethylhexylene, 2-propylpentylene, n-nonylene, 2,2-dimethylheptylene, 1-ethyl-propylene, 1,1-dimethyl-propylene, isohexylene, 4-methylhexylene, 5-methylhexylene, and the like. In the present disclosure, the "alkylene" is optionally substituted, and the substituent is optionally one or more substituents selected from the group consisting of D (i.e., deuterium), halogen, hydroxy, cyano, C1-C3 alkoxy, trifluoromethyl, heterocyclyl (e.g., 4- to 8-membered heterocyclyl), nitro, mercapto, carbonyl, ester group, imido group, amino, phosphine oxide group, alkoxy, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, deuterated alkyl, alkyl halide, amino-substituted alkylene, alkyl-NHC(O)-, alkyl-C(O)NH-, cycloalkyl, deuterated cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, acenaphthenyl, oxo group, or any combination thereof.

[0046] The term "alkoxy," as used herein, alone or in combination, refers to O-alkyl. Optionally, the alkyl portion of the alkoxy can contain 1-10 (or 1-6, 1-5, 1-4, or 1-3) carbon atoms. Alkoxy can include, but is not limited to, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentoxy, isopentyloxy, n-hexyloxy, 3,3-dimethylbutoxy, 2-ethylbutoxy, n-octyloxy, n-nonyloxy, n-decyloxy, and the like.

[0047] As used herein, the terms "halogen" and "halogenated", alone or in combination, refer to fluorine, chlorine, bromine, or iodine.

[0048] As used herein, the term "halogenated alkyl," alone or in combination, refers to a straight- or branched-chain alkyl in which one or more hydrogen atoms have been replaced with a halogen atom. Examples of halogenated alkyl include, but are not limited to, -CF, -CHF, -CHF, -CBr, -CHBr, -CC, -CHC, -CHCl, -CI, -CHI, -CHI, -CHI, -CH-CF, -CH-CHF, -CH-CHF, -CH-CBr, -CH-CHBr, -CH-CHBr, -CH-CC, -CH-CHCl, -CH-CHCl, -CH-CI, -CH-CHI, -CH-CHI, and the like, wherein alkyl and halogen are as defined above.

[0049] As used herein, the term "halogenated alkoxy," used alone or in combination, refers to an alkoxy in which one or more hydrogen atoms are each replaced with a halogen atom. Examples of halogenated alkoxy include, but are not limited to, trifluoromethoxy, etc., wherein the alkoxy and halogen are as defined above.

[0050] As used herein, the term "pharmaceutically acceptable carrier" refers to a carrier typically used in administering therapeutic agents, which does not itself induce the production of antibodies harmful to the individual receiving the composition, and does not cause excessive toxicity after administration. These carriers are well known to those skilled in the art, and relevant content regarding pharmaceutically acceptable carriers is disclosed, for example, in Remington's Pharmaceutical Sciences (Mack Pub. Co., NJ 1991). Specifically, the carrier may include, but is not limited to, one or more combinations of saline, buffer solution, glucose, water, glycerol, ethanol, adjuvants, and the like.

[0051] As used herein, the term "pharmaceutically acceptable excipient" refers to a pharmaceutically acceptable material, such as a filler, stabilizer, dispersant, suspending agent, diluent, excipient, thickener, solvent, or sealant, that can be carried or delivered to a patient's body or administered to a patient to perform a desired function with the compounds useful in the present disclosure. Generally, such constructs are carried or delivered from one organ or part of the body to another organ or part of the body. An excipient must be "acceptable" in that it is compatible with the other ingredients of the formulation (including the compounds useful in the present disclosure) and is not harmful to the patient. Some examples of pharmaceutically acceptable excipients that may be used include, but are not limited to, sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethylcellulose, ethyl cellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc; additives such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol; polyols such as glycerol, sorbitol, mannitol, and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; surfactants, phosphate buffers; and other non-toxic compatible substances used in drug formulations. compound

[0052] In one aspect, the present disclosure provides, in embodiment 1): a compound of the chemical structure represented by Formula I, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, [ka] Formula I In Formula I, X is selected from CO or CH2; L1 is selected from S or O; X1 is selected from the group consisting of substituted or unsubstituted straight or branched chain alkylene, or X1 is absent; X2 represents a structure of formula II; [ka] Formula II In Formula II, ring A and ring B are each independently selected from the group consisting of substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, substituted or unsubstituted heterocyclylene, or substituted or unsubstituted cycloalkylene; t represents an integer of 0, 1, or 2; and The symbol # indicates the connection point with X3; X3 is selected from the group consisting of CR1, N, or CO, where R1 is selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, trifluoromethoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched alkyl, or substituted or unsubstituted cycloalkyl; R a1 is selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocyclyl; R a2 is selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocyclyl, or R a2 is absent; and when X3 represents CO, R a2does not exist and R a1 is not hydrogen or deuterium, and R a2 represents hydrogen or deuterium, X3 represents CR1 or N, and R a1 is not hydrogen or deuterium; R a is selected from the group consisting of deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, halogenated alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R b1 , R b2 , R b3 , R b4 and R b5 are each independently selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, halogenated alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, and substituted or unsubstituted linear or branched alkyl; n represents an integer of 0, 1, 2, or 3, and when n represents an integer of 2 or 3, each R a are the same or different.

[0053] Embodiment 2): Compounds of formula I according to embodiment 1) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein X in formula I is CO.

[0054] Embodiment 3): Compounds of formula I according to embodiment 1) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein X in formula I is CH2.

[0055] Embodiment 4): Compounds of formula I according to embodiment 1) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein L1 in formula I is S.

[0056] Embodiment 5): Compounds of formula I according to embodiment 1) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein L1 in formula I is O.

[0057] In embodiment 6), the compound of formula I according to any one of embodiments 1 to 5, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein X1 is a substituted or unsubstituted linear or branched alkylene. When X1 is a substituted or unsubstituted linear or branched alkylene, said X1 may be a substituted or unsubstituted linear or branched C1-C5 alkylene, or a substituted or unsubstituted linear or branched C1-C3 alkylene, etc.

[0058] In embodiment 7), the compound of formula I according to any one of embodiments 1) to 6) or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein when X1 is a substituted or unsubstituted linear or branched C1-C5 alkylene, the linear or branched C1-C5 alkylene may be methylene, ethylene, propylene, n-propylene, isopropylene, butylene, n-butylene, isobutylene, tert-butylene, sec-butylene, 1-methyl-butylene, 1-ethyl-butylene, pentylene, n-pentylene, isopentylene, neopentylene, tert-pentylene, etc.

[0059] In embodiment 8), with respect to a compound of formula I according to any one of embodiments 1) to 7), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein when X1 is a substituted or unsubstituted linear or branched C1-C3 alkylene, the linear or branched alkylene can be, for example, methylene, ethylene, propylene, or isopropylene.

[0060] In embodiment 9), the compound of formula I according to any one of embodiments 1) to 8) or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein X1 is selected from methylene.

[0061] In embodiment 10), the present invention relates to a compound of formula I according to any one of embodiments 1) to 8), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein the substituted substituents of said X1 are optionally selected from the group consisting of deuterium, halogen, cyano, nitro, hydroxy, mercapto, carbonyl, ester group, imido group, amino, phosphine oxide group, alkoxy, halogenated alkoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, and heteroaryl, acenaphthenyl, etc., or any combination thereof. Optionally, the substituent of the substituted X1 may be, for example, one or more substituents selected from the group consisting of D (i.e., deuterium), halogen, hydroxy, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl (e.g., a 4- to 8-membered heterocycle), nitro, mercapto, carbonyl, ester group, imido group, amino, phosphine oxide group, alkoxy, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, deuterated alkyl, alkyl halide, amino-substituted alkylene, alkyl-NHC(O)-, alkyl-C(O)NH-, cycloalkyl, deuterated cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, acenaphthenyl, oxo group, or any combination thereof. Further optionally, the substituents of the substituted X1 may be selected from the group consisting of, for example, deuterium, halogen, nitro, mercapto, hydroxy, cyano, C1-C3 alkyl, C1-C3 alkoxy, halogenated C1-C3 alkoxy, halogenated C1-C3 alkyl, amino, silyl, boryl, or any combination thereof.Further optionally, the substituents of "substituted" may be selected from the group consisting of, for example, deuterium, F, Cl, methoxy, methyl, hydroxy, or any combination.

[0062] In embodiment 11), the compound of formula I according to any one of embodiments 1) to 5) or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein X1 is absent.

[0063] In embodiment 12), the compound of formula I according to any one of embodiments 1) to 11), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein X2 represents the structure of formula II, [ka] Formula II In Formula II, ring A is a substituted or unsubstituted C5-C 30 arylene, substituted or unsubstituted 5- to 30-membered heteroarylene, substituted or unsubstituted 4- to 30-membered heterocyclylene, or substituted or unsubstituted C3-C 30 cycloalkylene; preferably, ring A is selected from the group consisting of substituted or unsubstituted C5-C 20 arylene, substituted or unsubstituted 5- to 20-membered heteroarylene, substituted or unsubstituted 4- to 20-membered heterocyclylene, or substituted or unsubstituted C3-C 20 cycloalkylene; Ring B is a substituted or unsubstituted C5-C 30 arylene, substituted or unsubstituted 5- to 30-membered heteroarylene, substituted or unsubstituted 4- to 30-membered heterocyclylene, or substituted or unsubstituted C3-C 30 cycloalkylene; preferably, Ring B is selected from the group consisting of substituted or unsubstituted C5-C 20 arylene, substituted or unsubstituted 5- to 20-membered heteroarylene, substituted or unsubstituted 4- to 20-membered heterocyclylene, or substituted or unsubstituted C3-C 20 cycloalkylene; t represents an integer of 0, 1, or 2; preferably, t represents an integer of 0 or 1; and The symbol # indicates the connection point with X3.

[0064] In embodiment 13), with respect to the compound of formula I according to any one of embodiments 1) to 12), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, X2 represents a structure of formula II, [ka] Formula II In Formula II, ring A is a substituted or unsubstituted C5-C 15 arylene, substituted or unsubstituted 5- to 15-membered heteroarylene, substituted or unsubstituted 4- to 15-membered heterocyclylene, or substituted or unsubstituted C3-C 15 cycloalkylene, wherein the substituents of said substituted Ring A are optionally one or more substituents selected from the group consisting of halogen, mercapto, hydroxy, amino, cyano, C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkyl, or any combination thereof; Ring B is a substituted or unsubstituted C5-C 15 arylene, substituted or unsubstituted 5- to 15-membered heteroarylene, substituted or unsubstituted 4- to 15-membered heterocyclylene, or substituted or unsubstituted C3-C 15 cycloalkylene; wherein the substituents of said substituted Ring B are optionally one or more substituents selected from the group consisting of halogen, mercapto, hydroxy, amino, cyano, C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkyl, or any combination thereof; t represents an integer of 0, 1, or 2; preferably, t represents an integer of 0 or 1; and The symbol # indicates the connection point with X3.

[0065] In embodiment 14), with respect to the compound of formula I according to any one of embodiments 1) to 13), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, ring A and ring B each independently represent one of the following groups: Azetidinylene, azacyclopentylene, azacyclohexylene, azacycloheptanylene, azacyclooctylene, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, dihydropyranylene, tetrahydrothienylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, dioxacyclohexylene, dioxacyclohexenylene, azacycloheptanylene, azacyclooctylene azacyclohexylene, azacycloheptanylene, azacyclooctylene, a bridged heterocyclylene (e.g., a 4- to 15-membered bridged heterocyclylene, a 5- to 15-membered bridged heterocyclylene, and a 7- to 15-membered bridged heterocyclylene, such as azabicyclohexylene, azabicycloheptanylene, or azabicyclooctylene), or a spiroheterocyclylene (e.g., a 4- to 15-membered spiroheterocyclylene, a 5- to 15-membered spiroheterocyclylene, and a 7- to 15-membered spiroheterocyclylene, such as 3-azaspiro[5.5]undecanylene or 7-azaspiro[3.5]nonanylene); or Furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzo isoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2 a]pyridylene, 1H-pyrrolo[3,2-b]pyridylene, 1H-pyrrolo[2,3-b]pyridylene, pyrrolo[2,1-b]thiazolylene and imidazo[2,1-b]thiazolylene; or Cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decalinylene, octahydrocyclopentalenylene, octahydro-1H-indenylene, spirocycloalkylene (e.g., C3-C 15 Spirocycloalkylene or C5-C 15 Spirocycloalkylene or C7-C 15 spirocycloalkylene, such as spiro[3.3]heptylene, spiro[2.5]octylene, spiro[3.5]nonylene, spiro[4.4]nonylene, spiro[4.5]decylene, or spiro[5.5]undecylene), or bridged cycloalkylene (e.g., C-C 15 Bridged cycloalkylene or C5-C 15 Bridged cycloalkylene or C7-C 15 a bridged cycloalkylene, such as adamantanylene, noradamantanylene, bornylene, biscyclo[2.2.1]heptylene, 2-oxobiscyclo[2.2.1]heptylene or biscyclo[2.2.1]heptenylene); or selected from the group consisting of phenylene or naphthylene; wherein the ring A and ring B are each independently optionally further substituted with one or more substituents selected from the group consisting of deuterium, halogen, nitro, mercapto, hydroxy, cyano, C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, halogenated C1-C6 alkyl, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, or any combination thereof.

[0066] In embodiment 15), with respect to the compound of formula I according to any one of embodiments 12) to 14), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, X2 represents an optionally substituted nitrogen-containing heterocyclyl, an optionally substituted aryl-NH2, an optionally substituted heteroaryl-NH2, or an optionally substituted cycloalkyl-NH2. [ka] and the like.

[0067] In embodiment 16), compounds of formula I according to embodiment 15) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R d1 , R d2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, halogenated C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched C1-C5 alkyl; and R d1 , R d2are not simultaneously hydrogen. In a specific embodiment, optionally, halogen may be, for example, F, Cl, Br, or I. Optionally, C1-C6 alkoxy may include, but is not limited to, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentoxy, isopentyloxy, n-hexyloxy, 3,3-dimethylbutoxy, 2-ethylbutoxy, etc. Optionally, halogenated C1-C6 alkoxy may be, for example, trifluoromethoxy, etc. Optionally, substituted or unsubstituted amino includes amino, N-methylamino, N-ethylamino, N-phenylamino, N,N-dimethylamino, N,N-diethylamino, etc. Optionally, substituted or unsubstituted silyl can be, for example, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, vinyldimethylsilyl, propyldimethylsilyl, triphenylsilyl, diphenylsilyl, phenylsilyl, etc. Optionally, substituted or unsubstituted boryl can include, for example, trimethylboryl, triethylboryl, tert-butyldimethylboryl, triphenylboryl, phenylboryl, etc. Optionally, straight or branched chain C1-C5 alkyl includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methyl-butyl, 1-ethyl-butyl, pentyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, etc. wherein the linear or branched C1-C5 alkyl is optionally substituted, and the substituent is optionally one or more substituents selected from the group consisting of D (i.e., deuterium), halogen, hydroxy, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl (e.g., a 4- to 8-membered heterocycle), or any combination thereof.

[0068] In embodiment 17), the compound of formula I according to any one of embodiments 1) to 16) or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein X3 is CR1; and R1 is selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, trifluoromethoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched alkyl, or substituted or unsubstituted cycloalkyl.

[0069] In embodiment 18), with respect to compounds of formula I according to embodiment 17) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R is hydrogen, deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, trifluoromethoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched C-C 10 Alkyl, or substituted or unsubstituted C3-C 15 cycloalkyl.

[0070] In embodiment 19), compounds of formula I according to embodiment 17) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein when X3 is selected from CR1: R1 is hydrogen.

[0071] In embodiment 20), the compounds of formula I according to embodiment 17) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein when X3 is selected from CR1: R1 is deuterium.

[0072] In embodiment 21), the compound of formula I according to embodiment 17) or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein when X3 is selected from CR1, R1 is halogen. Optionally, when R1 is halogen, the halogen is F, Cl, Br, or I.

[0073] In embodiment 22), compounds of formula I according to embodiment 17) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein when X3 is selected from CR1: R1 is nitro.

[0074] In embodiment 23), compounds of formula I according to embodiment 17) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein when X3 is selected from CR1: R1 is cyano.

[0075] In embodiment 24), compounds of formula I according to embodiment 17) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein when X3 is selected from CR1: R1 is amino.

[0076] In embodiment 25), compounds of formula I according to embodiment 17) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein when X3 is selected from CR1: R1 is hydroxy.

[0077] In embodiment 26), compounds of formula I according to embodiment 17) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein when X3 is selected from CR1: R1 is mercapto.

[0078] In embodiment 27), compounds of formula I according to embodiment 17) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein when X3 is selected from CR1: R1 is trifluoromethoxy.

[0079] In embodiment 28), the compound of formula I according to embodiment 17) or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein when X is selected from CR, R is substituted or unsubstituted amino. Optionally, substituted or unsubstituted amino includes amino, N-methylamino, N-ethylamino, N-phenylamino, N,N-dimethylamino, N,N-diethylamino, etc.

[0080] In embodiment 29), the compound of formula I according to embodiment 17) or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein when X is selected from CR, R is substituted or unsubstituted silyl. Optionally, the substituted or unsubstituted silyl is specifically trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, vinyldimethylsilyl, propyldimethylsilyl, triphenylsilyl, diphenylsilyl, phenylsilyl, etc.

[0081] In embodiment 30), the compound of formula I according to embodiment 17) or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein when X is selected from CR, R is substituted or unsubstituted boryl. Optionally, the substituted or unsubstituted boryl is specifically trimethylboryl, triethylboryl, tert-butyldimethylboryl, triphenylboryl, phenylboryl, etc.

[0082] In embodiment 31), compounds of formula I according to embodiment 17) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein when X3 is selected from CR1, R1 is substituted or unsubstituted alkyl. Optionally, when R1 is substituted or unsubstituted linear or branched alkyl, the number of carbon atoms can be, for example, C1-C 30 , C1-C 25 , C1-C 20 , C1-C 15 , C1-C 10 , C1-C5, C1-C3, etc. Preferably, it is a straight or branched C1-C 10 and optionally straight or branched C-C alkyl. 10Alkyl includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methylbutyl, 1-ethylbutyl, pentyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 4-methyl-2-pentyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl, n-heptyl, 1-methylhexyl, cyclopentylmethyl, cyclohexylmethyl, octyl, n-octyl, tert-octyl, 1-methylheptyl, 2-ethylhexyl, 2-propylpentyl, n-nonyl, 2,2-dimethylheptyl, 1-ethylpropyl, 1,1-dimethylpropyl, isohexyl, 4-methylhexyl, 5-methylhexyl, etc. Optionally, straight or branched C-C 10 Alkyl includes, but is not limited to, methyl, ethyl, propyl, etc. Furthermore, the alkyl is optionally substituted, and the substituent may be selected from the group consisting of, for example, deuterium, halogen, cyano, nitro, hydroxy, mercapto, carbonyl, ester group, imide group, amino, phosphine oxide group, alkoxy, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, deuterated alkyl, alkyl halide, amino-substituted alkylene, alkyl-NHC(O)-, alkyl-C(O)NH-, cycloalkyl, deuterated cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, acenaphthenyl, oxo group, or any combination thereof. The substituents are preferably one or more substituents selected from the group consisting of D (i.e., deuterium), halogen, hydroxy, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl (e.g., a 4- to 8-membered heterocycle), or any combination thereof.

[0083] In embodiment 32), the compound of formula I according to embodiment 17) or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein R is substituted or unsubstituted cycloalkyl, and R is substituted or unsubstituted cycloalkyl having 3 to 20 carbon atoms (i.e., C 3-20 cycloalkyl), or 3 to 15 carbon atoms (i.e., C 3-15 cycloalkyl), 3 to 12 carbon atoms (i.e., C 3-12 cycloalkyl), or 3 to 11 carbon atoms (i.e., C 3-11 cycloalkyl), or 3 to 10 carbon atoms (i.e., C 3-10 cycloalkyl), or 3 to 8 carbon atoms (i.e., C 3-8 cycloalkyl), or 3 to 7 carbon atoms (i.e., C 3-7 cycloalkyl), or 3 to 6 carbon atoms (i.e., C 3-6 Preferably, R1 is a substituted or unsubstituted C3-C 15 cycloalkyl. Optionally, C3-C 15 Cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C 5-20 Spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), adamantanyl, noradamantanyl, bornyl, norbornyl (IUPAC systematic name is biscyclo[2.2.1]heptyl), and cubanylene, and the like. Optionally, C3-C 15Cycloalkyl includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and the like. wherein the cycloalkyl is optionally substituted, and the substituent is optionally one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents selected from the group consisting of trifluoromethyl, mercapto, hydroxy, amino, halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl, deuterium, nitro, carbonyl, ester group, imido group, amino, phosphine oxide group, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, deuterated alkyl, amino-substituted alkylene, alkyl-NHC(O)—, alkyl-C(O)NH—, cycloalkyl, deuterated cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, acenaphthenyl, oxo group, or any combination thereof. Preferably, the substituents are selected from the group consisting of trifluoromethyl, mercapto, hydroxy, amino, halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethoxy, heterocyclyl, or any combination thereof.

[0084] In embodiment 33), the compound of formula I according to any one of embodiments 1) to 17), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein X3 is N.

[0085] In embodiment 34), the compound of formula I according to any one of embodiments 1) to 17), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein X3 is CO.

[0086] In embodiment 35), compounds of formula I according to any one of embodiments 1) to 17) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein when X3 represents CO, R a2does not exist and R a1 is not hydrogen or deuterium.

[0087] In embodiment 36), a compound of formula I according to any one of embodiments 1) to 17), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein R a2 represents hydrogen or deuterium, X3 represents CR1 or N, and R a1 is not hydrogen or deuterium.

[0088] In embodiment 37), with respect to a compound of formula I according to any one of embodiments 1) to 36), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, R a1 is selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocyclyl.

[0089] In embodiment 38), with respect to compounds of formula I according to embodiment 37) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a1 is hydrogen, deuterium, substituted or unsubstituted C5-C 30 Aryl, substituted or unsubstituted 5-30 membered heteroaryl, substituted or unsubstituted C3-C 30 cycloalkyl, or substituted or unsubstituted 4- to 30-membered heterocyclyl; preferably, R a1 is hydrogen, deuterium, substituted or unsubstituted C5-C 20 Aryl, substituted or unsubstituted 5-20 membered heteroaryl, substituted or unsubstituted C3-C 20 It is selected from the group consisting of cycloalkyl, or substituted or unsubstituted 4- to 20-membered heterocyclyl.

[0090] In embodiment 39) compounds of formula I according to embodiment 37) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a1 is hydrogen.

[0091] In embodiment 40) compounds of formula I according to embodiment 37) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a1 is deuterium.

[0092] In embodiment 41), compounds of formula I according to embodiment 37) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a1 is a substituted or unsubstituted aryl. Optionally, the substituted or unsubstituted aryl is a substituted or unsubstituted C-C 30 aryl. Optionally, substituted or unsubstituted C5-C 30 Aryl is a substituted or unsubstituted C5-C 25 , C5-C 20 , C5-C 15 aryl. Optionally, C5-C 30The aryl may be a monocyclic aryl or a polycyclic aryl. In some embodiments, monocyclic aryls include, but are not limited to, phenyl, biphenyl, terphenyl, quaterphenyl, quinquephenyl, etc. Polycyclic aryls include, but are not limited to, naphthyl, anthryl, phenanthryl, pyrenyl, perylenyl, fluorenyl, etc. The fluorenyl may be substituted, for example, 9,9'-dimethylfluorenyl, 9,9'-diphenylfluorenyl, etc. Two substituents may also be bonded to each other to form a spiro ring structure, for example, 9,9'-spirobifluorenyl, etc. The aryl may be optionally substituted. Substituted aryl refers to aryl (e.g., aryl mono-, di-, or tri-substituted with substituents) that is substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent, where the substituents are, for example, optionally deuterated C1-C6 alkyl, deuterated C3-C6 cycloalkyl, deuterium, hydroxy, amino, mercapto, halogen, cyano, nitro, carbonyl, an ester group, an imide group, a phosphine oxide group, trifluoromethoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, or the like. and any combination thereof.Preferably, the substituents are selected from the group consisting of deuterated C1-C6 alkyl, deuterated C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, and any combination thereof. a1 is a substituted aryl and the substituent of the aryl is a substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C 10 cycloalkyl and substituted or unsubstituted C3-C6 cycloalkyl); optionally, cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl or C5-C 15 Spirocycloalkyl or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged cycloalkyl or C5-C 15 Bridged cycloalkyl or C7-C 15bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy, Further, R is selected from the group consisting of hydroxy, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. a1 is a substituted aryl, and the substituent of the aryl is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl is a substituted or unsubstituted C5-C 20 Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl and substituted or unsubstituted C5-C 10 aryl, etc.) (optionally, the substituted or unsubstituted aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; the substituted or unsubstituted aryl is an optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituent is selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof). Furthermore, Ra1is substituted aryl and the aryl substituent is substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is selected from the group consisting of substituted or unsubstituted 5-25 membered heteroaryl (e.g., substituted or unsubstituted 5-20 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl, or substituted or unsubstituted 5-10 membered heteroaryl); optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, xanthyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, quinazolinyl, quinazinyl, quinoxalinyl, naphthyridinyl, acridinyl, quinazolinyl, quinazinyl, quinazinyl, quinazinyl, quinazinyl, quinazinyl, quinazinyl, quinazinyl, naphthyridinyl, acridinyl, quinazin ... inthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, selected from the group consisting of indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Further, R; a1 When is substituted aryl and the aryl substituent is substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is selected from the group consisting of substituted or unsubstituted 4-20 membered heterocyclyl (e.g., substituted or unsubstituted 4-15 membered heterocyclyl, substituted or unsubstituted 4-10 membered heterocyclyl, or substituted or unsubstituted 4-8 membered heterocyclyl, etc.); optionally, the heterocyclyl is selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, nyl, thiomorpholinyl, dioxacyclohexyl, dioxacyclohexenyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl or 5- to 15-membered bridged heterocyclyl, 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl, diazabicyclooctyl), or spiroheterocyclyl (e.g., 4- to 15-membered spiroheterocyclyl or 5- to 15-membered spiroheterocyclyl, 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl). heterocyclyl is an optionally substituted heterocyclyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0093] In embodiment 42) compounds of formula I according to embodiment 37) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a1 is a substituted or unsubstituted heteroaryl. a1is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5- to 30-membered heteroaryl. Optionally, the substituted or unsubstituted 5- to 30-membered heteroaryl is a substituted or unsubstituted 5- to 15-membered, 5- to 12-membered, 5- to 11-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7-membered, 5- to 6-membered, 6- to 15-membered, or 6- to 9-membered heteroaryl. Optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, cinnolinyl, naphthyridinyl, acridinyl, xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyrazolopyridyl, pyrazolopyrimidinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyrazinyl, Examples of heteroaryl include, but are not limited to, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, isobenzofuranyl, dibenzothienyl, dibenzofuranyl, indazolyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, pyrrolopyridinyl, pyrrolothiazolyl, imidazothiazolyl, pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, and naphthobenzothienyl, and the like, wherein the heteroaryl may be substituted or unsubstituted.Substituted heteroaryl refers to heteroaryl substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent, wherein the substituents are optionally selected from the group consisting of C-C alkyl, C-C cycloalkyl, hydroxy, amino, mercapto, halogen, deuterium, nitro, carbonyl, an ester group, an imido group, a phosphine oxide group, trifluoromethoxy, C-C alkoxy, C-C alkylamino, halogenated C-C alkyl, amino-substituted C-C alkylene, C-C alkyl-NHC(O)—, C-C alkyl-C(O)NH—, cyano, alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino group, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, acenaphthenyl, or any combination thereof. Preferably, the substituents are optionally selected from the group consisting of C1-C3 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen, C1-C3 alkoxy, C1-C3 alkylamino, halogenated C1-C3 alkyl, amino-substituted C1-C3 alkylene, C1-C3 alkyl-NHC(O)-, C1-C3 alkyl-C(O)NH-, cyano, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or any combination thereof. a1 is a substituted heteroaryl and the substituent of the heteroaryl is a substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C 10cycloalkyl, and substituted or unsubstituted C3-C6 cycloalkyl; optionally, cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl or C5-C 15 Spirocycloalkyl or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged cycloalkyl or C5-C 15 Bridged cycloalkyl or C7-C 15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy, Further, R is selected from the group consisting of hydroxy, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. a1 is a substituted heteroaryl, and the substituent of the heteroaryl is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl is a substituted or unsubstituted C5-C 20 Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl and substituted or unsubstituted C5-C10 aryl, etc.); optionally, aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; aryl is an optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Further, R a1is a substituted heteroaryl, and the substituent of the heteroaryl is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5-25 membered heteroaryl (e.g., a substituted or unsubstituted 5-20 membered heteroaryl, a substituted or unsubstituted 5-15 membered heteroaryl, or a substituted or unsubstituted 5-10 membered heteroaryl) (optionally, the substituted or unsubstituted heteroaryl is pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, xanthyl, thenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, selected from the group consisting of indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The substituted or unsubstituted heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Further, R; a1 is a substituted heteroaryl and the heteroaryl substituent is a substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is selected from the group consisting of substituted or unsubstituted 4- to 20-membered heterocyclyl (e.g., substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted 4- to 10-membered heterocyclyl, or substituted or unsubstituted 4- to 8-membered heterocyclyl, etc.); optionally, the heterocyclyl is selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, azacyclohexyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl or 5- to 15-membered bridged heterocyclyl or 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (e.g., 4- to 15-membered spiroheterocyclyl or 5- to 15-membered spiroheterocyclyl or 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); The cyclyl is an optionally substituted heterocyclyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0094] In embodiment 43) compounds of formula I according to embodiment 37) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a1 is a substituted or unsubstituted cycloalkyl. a1 is a substituted or unsubstituted cycloalkyl, said substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C-C 20 , C3-C 15 , C3-C 12 , C3-C 11 , C3-C 10, C3-C8, C3-C7, C3-C6 cycloalkyl, etc. Optionally, cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl or C5-C 15 Spirocycloalkyl or C7-C 15Spirocycloalkyls include, but are not limited to, spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), where the "cycloalkyl" is optionally substituted, and the substituents include trifluoromethyl, mercapto, hydroxy, amino, halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl, deuterium, nitro, carbonyl, ester group, imido group, amino, phosphine oxide group, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, deuterated alkyl, amino-substituted alkylene, alkyl-NH Preferably, the substituents are one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) selected from the group consisting of C(O)—, alkyl-C(O)NH—, substituted or unsubstituted cycloalkyl, deuterated cycloalkyl, alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, acenaphthenyl, oxo group, or any combination thereof. Furthermore, the substituents are preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents selected from the group consisting of trifluoromethyl, mercapto, hydroxy, amino, halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or any combination thereof. a1 is a substituted cycloalkyl, and the cycloalkyl substituent is a substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C10 cycloalkyl, and substituted or unsubstituted C3-C6 cycloalkyl, etc. (optionally, the substituted or unsubstituted cycloalkyl may be cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl or C5-C 15 Spirocycloalkyl or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged cycloalkyl or C5-C 15 Bridged cycloalkyl or C7-C 15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; where, when the substituted or unsubstituted cycloalkyl is a substituted cycloalkyl, the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy, C-C cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, deuterated C-C alkoxy, C-C alkylamino, halogenated C-C alkyl, halogenated C-C cycloalkyl, amino-substituted C-C alkylene, C-C alkyl-NHC(O)-, C-C alkyl-C(O)NH-, and any combination thereof. a1 is a substituted cycloalkyl, and the substituent of the cycloalkyl is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl is a substituted or unsubstituted C5-C 20Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl and substituted or unsubstituted C5-C 10 aryl, etc.); optionally, aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; aryl is an optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. a1is a substituted cycloalkyl and the cycloalkyl substituent is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is selected from the group consisting of substituted or unsubstituted 5-25 membered heteroaryl (e.g., substituted or unsubstituted 5-20 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl, or substituted or unsubstituted 5-10 membered heteroaryl); optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acryloyl, benzo ... Lysinyl, xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarba selected from the group consisting of zolyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Further, R; a1is a substituted cycloalkyl and the cycloalkyl substituent is a substituted or unsubstituted heterocyclyl, the heterocyclyl is selected from the group consisting of substituted or unsubstituted 4-20 membered heterocyclyl (e.g., substituted or unsubstituted 4-15 membered heterocyclyl, substituted or unsubstituted 4-10 membered heterocyclyl, or substituted or unsubstituted 4-8 membered heterocyclyl, etc.); optionally, the heterocyclyl is selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, dioxacyclohexenyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl or 5- to 15-membered bridged heterocyclyl or 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (e.g., 4- to 15-membered spiroheterocyclyl or 5- to 15-membered spiroheterocyclyl or 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); heterocyclyl is an optionally substituted heterocyclyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), such as The substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0095] In embodiment 44) compounds of formula I according to embodiment 37) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a1 is a substituted or unsubstituted heterocyclyl. a1is a substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is a substituted or unsubstituted 4- to 30-membered heterocyclyl, 4- to 25-membered heterocyclyl, 4- to 20-membered heterocyclyl, 4- to 15-membered heterocyclyl, 4- to 10-membered heterocyclyl, 10- to 15-membered heterocyclyl, 5- to 15-membered heterocyclyl, 7- to 15-membered heterocyclyl, etc. Optionally, the heterocyclyl contains 1 to 3 heteroatoms, or 1 to 2 heteroatoms, or 1 heteroatom, etc. Each heteroatom is independently selected from the group consisting of O, N, S, etc. Further optionally, the heterocyclyl is azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, triazolyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, dioxacyclohexenyl, azacycloheptanyl, diazacycloheptanyl (e.g., 1,4-diazacycloheptanyl, 4,5 ... Heptanyl, or 1,3-diazacycloheptanyl, etc.), azabicyclohexyl (e.g., 3-azabicyclo[3.1.0]hexyl, etc.), azabicycloheptanyl (e.g., 3-azabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.2.0]heptanyl, etc.), azabicyclooctyl (e.g., cis-7-azabicyclo[3.3.0]octyl, etc.), and spiroheterocyclyl (e.g., 7-azaspiro[3.5]nonanyl, 3-azaspiro[5.5]undecanyl, etc.).The heterocyclyl may be unsubstituted or substituted (e.g., mono-, di-, tri-, or poly-substituted) as clearly defined, where the substituents are optionally deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, carbonyl, ester, imido, phosphine oxide, trifluoromethoxy, oxo, optionally deuterated 1-C alkyl, halogenated C1-C6 alkyl, optionally deuterated 3-C6 cycloalkyl, optionally deuterated 1-C6 alkyl, optionally deuterated 2 ... and any combination thereof. Preferably, the substituents are selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated 1-C6 alkyl, halogenated C1-C6 alkyl, optionally deuterated 3-C6 cycloalkyl, optionally deuterated 1-C6 alkoxy, C1-C4 alkyl-NH-, NH2-C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, and any combination thereof. a1 is a substituted heterocyclyl and the heterocyclyl substituent is a substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C-C 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C 10cycloalkyl, and substituted or unsubstituted C3-C6 cycloalkyl; optionally, cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl or C5-C 15 Spirocycloalkyl or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged cycloalkyl or C5-C 15 Bridged cycloalkyl or C7-C 15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy, Further, R is selected from the group consisting of hydroxy, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. a1 is a substituted heterocyclyl and the substituent of the heterocyclyl is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl is a substituted or unsubstituted C5-C 20 Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl and substituted or unsubstituted C5-C10 aryl, etc.); optionally, the aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; the aryl is an optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. a1is a substituted heterocyclyl and the heterocyclyl substituent is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is selected from the group consisting of substituted or unsubstituted 5-25 membered heteroaryl (e.g., substituted or unsubstituted 5-20 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl, or substituted or unsubstituted 5-10 membered heteroaryl); optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl , xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl phenyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Further, R; a1 is a substituted heterocyclyl, and the heterocyclyl substituent is a substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is a substituted or unsubstituted 4- to 20-membered heterocyclyl (e.g., a substituted or unsubstituted 4- to 15-membered heterocyclyl, a substituted or unsubstituted 4- to 10-membered heterocyclyl, or a substituted or unsubstituted 4- to 8-membered heterocyclyl, etc.) (optionally, the substituted or unsubstituted heterocyclyl is azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohex ... azacyclohexenyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl or 5- to 15-membered bridged heterocyclyl or 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (e.g., 4- to 15-membered spiroheterocyclyl or 5- to 15-membered spiroheterocyclyl or 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); the substituted or unsubstituted heterocyclyl is optionally substituted. The number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and the substituents are, for example, selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0096] In embodiment 45), a compound of formula I according to any one of embodiments 1) to 44), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein R a2 is selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocyclyl, or R a2 is absent; and when X3 represents CO, R a2 does not exist and R a1 is not hydrogen or deuterium, and R a2 represents hydrogen or deuterium, X3 represents CR1 or N, and R a1 is not hydrogen or deuterium.

[0097] In embodiment 46), compounds of formula I according to embodiment 45) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a2 is hydrogen, deuterium, substituted or unsubstituted C5-C 30 Aryl, substituted or unsubstituted 5-30 membered heteroaryl, substituted or unsubstituted C3-C 30 cycloalkyl, or substituted or unsubstituted 4- to 30-membered heterocyclyl, or R a2 does not exist.

[0098] In embodiment 47) compounds of formula I according to embodiment 45) or 46) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a2 is hydrogen, deuterium, substituted or unsubstituted C5-C 20 Aryl, substituted or unsubstituted 5-20 membered heteroaryl, substituted or unsubstituted C3-C 20 cycloalkyl, or substituted or unsubstituted 4- to 20-membered heterocyclyl, or R a2 does not exist.

[0099] In embodiment 48), the compound of formula I according to any one of embodiments 45) to 47), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein R a2 is selected from hydrogen.

[0100] In embodiment 49), the compound of formula I according to any one of embodiments 45) to 47), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein R a2 is selected from deuterium.

[0101] In embodiment 50), compounds of formula I according to embodiment 45) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a2 is a substituted or unsubstituted C5-C 20 Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl, substituted or unsubstituted C5-C 10The aryl may be a monocyclic aryl or a polycyclic aryl. In some embodiments, the monocyclic aryl includes, but is not limited to, phenyl, biphenyl, terphenyl, quaterphenyl, penta-biphenyl, and the like. The polycyclic aryl includes, but is not limited to, naphthyl, anthryl, phenanthryl, pyrenyl, perylenyl, fluorenyl, and the like. The fluorenyl may be substituted, for example, 9,9'-dimethylfluorenyl, 9,9'-diphenylfluorenyl, and the like. Preferably, R a2is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, and 9,9'-dimethylfluorenyl. Two of the substituents may be bonded to each other to form a spiro ring structure, such as 9,9'-spirobifluorenyl. The aryl is an optionally substituted aryl. Substituted aryl refers to an aryl substituted once or multiple times (e.g., 1-4, 1-3, or 1-2 times) with a substituent (e.g., an aryl mono-, di-, or tri-substituted with a substituent), where the substituent is optionally selected from, for example, deuterated C1-C6 alkyl, deuterated C3-C6 cycloalkyl, deuterium, hydroxy, amino, mercapto, halogen, cyano, nitro, carbonyl, ester group, imide group, phosphine oxide group, trifluoromethoxy, deuterated C1-C6 alkoxy, and C1-C4 alkylamino. , halogenated C1-C6 alkyl, amino substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, alkyl, substituted or unsubstituted cycloalkyl, alkenyl, substituted or unsubstituted aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino group, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, acenaphthenyl, and any combination thereof. Preferably, the substituents are selected from the group consisting of deuterated C1-C6 alkyl, deuterated C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, and any combination thereof. a2 is a substituted aryl and the substituent of the aryl is a substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C 20Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C 10 cycloalkyl, and substituted or unsubstituted C3-C6 cycloalkyl; optionally, cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl or C5-C 15 Spirocycloalkyl or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged cycloalkyl or C5-C 15 Bridged cycloalkyl or C7-C 15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy, Further, R is selected from the group consisting of hydroxy, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. a2 is a substituted aryl, and the substituent of the aryl is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl is a substituted or unsubstituted C5-C20 Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl and substituted or unsubstituted C5-C 10 aryl, etc.) (optionally, the substituted or unsubstituted aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; the substituted or unsubstituted aryl is an optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituent is selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof). Furthermore, R a2is substituted aryl and the aryl substituent is substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is selected from the group consisting of substituted or unsubstituted 5-25 membered heteroaryl (e.g., substituted or unsubstituted 5-20 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl, or substituted or unsubstituted 5-10 membered heteroaryl); optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, xanthyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, quinazolinyl, quinazinyl, quinoxalinyl, naphthyridinyl, acridinyl, quinazolinyl, quinazinyl, quinazinyl, quinazinyl, quinazinyl, quinazinyl, quinazinyl, quinazinyl, naphthyridinyl, acridinyl, quinazin ... inthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, selected from the group consisting of indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Further, R; a2 is a substituted aryl and the aryl substituent is a substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is selected from the group consisting of substituted or unsubstituted 4-20 membered heterocyclyl (e.g., substituted or unsubstituted 4-15 membered heterocyclyl, substituted or unsubstituted 4-10 membered heterocyclyl, or substituted or unsubstituted 4-8 membered heterocyclyl, etc.); optionally, the heterocyclyl is selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, dioxacyclohexenyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl or 5- to 15-membered bridged heterocyclyl or 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (e.g., 4- to 15-membered spiroheterocyclyl or 5- to 15-membered spiroheterocyclyl or 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); heterocyclyl is optionally substituted. The number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0102] In embodiment 51) compounds of formula I according to embodiment 45) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a2 is selected from the group consisting of substituted or unsubstituted 5- to 25-membered heteroaryl (preferably substituted or unsubstituted 5- to 20-membered heteroaryl, or substituted or unsubstituted 5- to 15-membered heteroaryl); more preferably, R a2is pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyraziny Heteroaryl is selected from the group consisting of benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, and naphthobenzothienyl, wherein the heteroaryl may be substituted or unsubstituted.Substituted heteroaryl refers to a heteroaryl substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent, wherein the substituents are optionally selected from the group consisting of C-C alkyl, C-C cycloalkyl, hydroxy, amino, mercapto, halogen, deuterium, nitro, carbonyl, an ester group, an imido group, a phosphine oxide group, trifluoromethoxy, C-C alkoxy, C-C alkylamino, halogenated C-C alkyl, amino-substituted C-C alkylene, C-C alkyl-NHC(O)—, C-C alkyl-C(O)NH—, cyano, alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino group, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, acenaphthenyl, or any combination thereof. Preferably, the substituents are optionally selected from the group consisting of C1-C3 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen, C1-C3 alkoxy, C1-C3 alkylamino, halogenated C1-C3 alkyl, amino-substituted C1-C3 alkylene, C1-C3 alkyl-NHC(O)-, C1-C3 alkyl-C(O)NH-, cyano, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or any combination thereof. a1 is a substituted heteroaryl and the substituent of the heteroaryl is a substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C 10cycloalkyl, and substituted or unsubstituted C3-C6 cycloalkyl; optionally, cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl or C5-C 15 Spirocycloalkyl or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged cycloalkyl or C5-C 15 Bridged cycloalkyl or C7-C 15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy, Further, R is selected from the group consisting of hydroxy, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. a2 is a substituted heteroaryl, and the substituent of the heteroaryl is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl is a substituted or unsubstituted C5-C 20 Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl and substituted or unsubstituted C5-C10 aryl, etc.); optionally, the aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; the aryl is an optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. a2is a substituted heteroaryl, and the substituent of the heteroaryl is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5-25 membered heteroaryl (e.g., a substituted or unsubstituted 5-20 membered heteroaryl, a substituted or unsubstituted 5-15 membered heteroaryl, or a substituted or unsubstituted 5-10 membered heteroaryl) (optionally, the substituted or unsubstituted heteroaryl is pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, , xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl phenyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The substituted or unsubstituted heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are optionally selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Further, R; a2 is a substituted heteroaryl, and the heteroaryl substituent is a substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is selected from the group consisting of substituted or unsubstituted 4- to 20-membered heterocyclyl (e.g., substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted 4- to 10-membered heterocyclyl, or substituted or unsubstituted 4- to 8-membered heterocyclyl, etc.); optionally, the heterocyclyl is selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, Pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, dioxacyclohexenyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl or 5- to 15-membered bridged heterocyclyl or 7- to 15-membered bridged heterocyclyl) 5-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (for example, 4- to 15-membered spiroheterocyclyl or 5- to 15-membered spiroheterocyclyl or 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); heterocyclyl is an optionally substituted heterocyclyl, and the number of substituents is preferably one or more (for example, 1-5, 1-4, 1-3, 1- 2 or 1), for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0103] In embodiment 52) ​​compounds of formula I according to embodiment 45) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a2 is selected from the group consisting of substituted or unsubstituted 4- to 20-membered heterocyclyl (e.g., substituted or unsubstituted 4- to 15-membered heterocyclyl); preferably, R a2is azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, dioxacyclohexenyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- 15-membered bridged heterocyclyl or 5- to 15-membered bridged heterocyclyl or 7- to 15-membered bridged heterocyclyl, for example, azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (for example, 4- to 15-membered spiroheterocyclyl or 5- to 15-membered spiroheterocyclyl or 7- to 15-membered spiroheterocyclyl, for example, 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl). The heterocyclyl may be unsubstituted or substituted (e.g., mono-, di-, tri-, or poly-substituted) as clearly defined, where the substituents are optionally deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, carbonyl, ester, imido, phosphine oxide, trifluoromethoxy, oxo, optionally deuterated 1-C alkyl, halogenated C-C alkyl, optionally deuterated 3-C cycloalkyl ... 6 alkoxy, C1-C4 alkyl-NH-, NH2-C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino group, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, acenaphthenyl, and any combination thereof.Preferably, the substituents are selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated 1-C6 alkyl, halogenated C1-C6 alkyl, optionally deuterated 3-C6 cycloalkyl, optionally deuterated 1-C6 alkoxy, C1-C4 alkyl-NH-, NH2-C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, and any combination thereof. a2 is a substituted heterocyclyl and the heterocyclyl substituent is a substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C-C 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C 10 cycloalkyl, and substituted or unsubstituted C3-C6 cycloalkyl; optionally, cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl or C5-C 15 Spirocycloalkyl or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged cycloalkyl or C5-C 15 Bridged cycloalkyl or C7-C 15bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy, Further, R is selected from the group consisting of hydroxy, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. a2 is a substituted heterocyclyl and the substituent of the heterocyclyl is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl is a substituted or unsubstituted C5-C 20 Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl and substituted or unsubstituted C5-C 10 aryl, etc.); optionally, the aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; the aryl is an optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. a2is a substituted heterocyclyl and the heterocyclyl substituent is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is selected from the group consisting of substituted or unsubstituted 5-25 membered heteroaryl (e.g., substituted or unsubstituted 5-20 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl, or substituted or unsubstituted 5-10 membered heteroaryl); optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl , xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl phenyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Further, R; a2 is a substituted heterocyclyl, and the heterocyclyl substituent is a substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is a substituted or unsubstituted 4- to 20-membered heterocyclyl (e.g., a substituted or unsubstituted 4- to 15-membered heterocyclyl, a substituted or unsubstituted 4- to 10-membered heterocyclyl, or a substituted or unsubstituted 4- to 8-membered heterocyclyl, etc.) (optionally, the substituted or unsubstituted heterocyclyl is azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, aryl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, dioxacyclohexenyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl or 5- to 15-membered bridged heterocyclyl or 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (e.g., 4- to 15-membered spiroheterocyclyl or 5- to 15-membered spiroheterocyclyl or 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); the substituted or unsubstituted heterocyclyl is an optionally substituted heterocyclyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0104] In embodiment 53) compounds of formula I according to embodiment 45) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a2 is a substituted or unsubstituted C3-C 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 cycloalkyl); preferably, R a2 is cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl or C5-C 15 Spirocycloalkyl or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged cycloalkyl or C5-C 15 Bridged cycloalkyl or C7-C 15and bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl, wherein the "cycloalkyl" is optionally substituted, and the substituents are preferably trifluoromethyl, mercapto, hydroxy, amino, halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl, deuterium, nitro, carbonyl, ester group, imido group, amino, phosphine oxide group, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, deuterated alkyl, amino-substituted alkylene, and aryl. and one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents selected from the group consisting of alkyl-NHC(O)-, alkyl-C(O)NH-, substituted or unsubstituted cycloalkyl, deuterated cycloalkyl, alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, acenaphthenyl, oxo group, or any combination thereof. Furthermore, the substituents are preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents selected from the group consisting of trifluoromethyl, mercapto, hydroxy, amino, halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or any combination thereof. a2 is a substituted cycloalkyl, and the cycloalkyl substituent is a substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C 10cycloalkyl, and substituted or unsubstituted C3-C6 cycloalkyl, etc. (optionally, the substituted or unsubstituted cycloalkyl may be cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl or C5-C 15 Spirocycloalkyl or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged cycloalkyl or C5-C 15 Bridged cycloalkyl or C7-C 15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; the substituted or unsubstituted cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy, , C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. a2 is a substituted cycloalkyl, and the substituent of the cycloalkyl is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl is a substituted or unsubstituted C5-C 20 Aryl (e.g., substituted or unsubstituted C5-C15 Aryl, substituted or unsubstituted C5-C 10 aryl, etc.); optionally, the aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; the aryl is an optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. a2is a substituted cycloalkyl and the cycloalkyl substituent is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is selected from the group consisting of substituted or unsubstituted 5-25 membered heteroaryl (e.g., substituted or unsubstituted 5-20 membered heteroaryl, substituted or unsubstituted 5-15 membered heteroaryl, or substituted or unsubstituted 5-10 membered heteroaryl); optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl , xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl phenyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Further, R; a2 is substituted cycloalkyl and the cycloalkyl substituent is substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is selected from the group consisting of substituted or unsubstituted 4-20 membered heterocyclyl (e.g., substituted or unsubstituted 4-15 membered heterocyclyl, substituted or unsubstituted 4-10 membered heterocyclyl, or substituted or unsubstituted 4-8 membered heterocyclyl, etc.); optionally, heterocyclyl is selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, cyclohexenyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl or 5- to 15-membered bridged heterocyclyl or 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (e.g., 4- to 15-membered spiroheterocyclyl or 5- to 15-membered spiroheterocyclyl or 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); heterocyclyl is an optionally substituted heterocyclyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0105] In embodiment 54), the compound of formula I according to any one of embodiments 45) to 53), or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein the substituted R a2 is optionally one or more substituents selected from the group consisting of deuterium, halogen, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, halogenated C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, linear or branched C1-C5 alkyl, halogenated C1-C5 alkyl, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted heterocyclyl. Further, optionally substituted alkyl can be, for example, optionally substituted C1-C 30 Alkyl, optionally substituted C-C 20 Alkyl, optionally substituted C-C 15 Alkyl and optionally substituted C-C 10The optionally substituted alkyl may be, for example, C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. The optionally substituted aryl may be, for example, an optionally substituted C5-C 30 Aryl, optionally substituted C5-C 25 Aryl, optionally substituted C5-C 15 Aryl and optionally substituted C5-C 10and aryl, wherein the substituents of the optionally substituted aryl are, for example, selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. The optionally substituted heteroaryl is, for example, an optionally substituted 5-30 membered heteroaryl, a substituted or unsubstituted 5-15 membered, 5-12 membered, 5-11 membered, 5-10 membered, 5-9 membered, 5-8 membered, 5-7 membered, 5-6 membered, 6-15 membered, or 6-9 membered heteroaryl, wherein the substituent of the optionally substituted heteroaryl is, for example, selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.The optionally substituted heterocyclyl is an optionally substituted 4- to 30-membered heterocyclyl, an optionally substituted 4- to 25-membered heterocyclyl, an optionally substituted 4- to 20-membered heterocyclyl, an optionally substituted 4- to 15-membered heterocyclyl, an optionally substituted 4- to 10-membered heterocyclyl, or an optionally substituted 10- to 15-membered heterocyclyl, wherein the substituents of the optionally substituted heterocyclyl are, for example, C1-C6 alkyl, C3-C6 cycloalkyl, hydroxyl ... and any combination thereof.

[0106] In embodiment 55), with respect to compounds of formula I according to embodiment 45) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a2 does not exist.

[0107] In embodiment 56), with respect to compounds of formula I according to embodiment 45) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a1 , R a2 cannot be both hydrogen and deuterium at the same time.

[0108] In embodiment 57), with respect to compounds of formula I according to embodiment 45) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a2 If is not present, X3 represents CO.

[0109] In embodiment 58), with respect to a compound of formula I according to any one of embodiments 1 to 53), 55), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, R a2 teeth [ka] selected from the group consisting of: wherein X6 is selected from the group consisting of deuterium, halogen, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, halogenated C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, halogenated C1-C6 alkyl, or straight or branched C1-C6 alkyl. Optionally, the halogen can be, for example, F, Cl, Br, or I. Optionally, the C1-C6 alkoxy can include, for example, but not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentoxy, isopentyloxy, n-hexyloxy, 3,3-dimethylbutoxy, 2-ethylbutoxy, and the like. Optionally, the halogenated C1-C6 alkoxy can be, for example, trifluoromethoxy, and the like. Optionally substituted or unsubstituted amino may include amino, N-methylamino, N-ethylamino, N-phenylamino, N,N-dimethylamino, N,N-diethylamino, etc. Optionally substituted or unsubstituted silyl may be, for example, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, vinyldimethylsilyl, propyldimethylsilyl, triphenylsilyl, diphenylsilyl, phenylsilyl, etc. Optionally substituted or unsubstituted boryl may include, for example, trimethylboryl, triethylboryl, tert-butyldimethylboryl, triphenylboryl, phenylboryl, etc. Optionally, the straight or branched C1-C6 alkyl includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methyl-butyl, 1-ethyl-butyl, pentyl, n-pentyl, isopentyl, neopentyl, and tert-pentyl, and the straight or branched C1-C6 alkyl is optionally substituted, wherein the substituent is optionally one or more substituents selected from the group consisting of D (i.e., deuterium), halogen, hydroxy, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl (e.g., a 4- to 8-membered heterocycle), or any combination thereof; m is an integer of 0, 1, 2, 3, 4, or 5, and when m is an integer of 2, 3, 4, or 5, each X6 is the same or different; X7 and X9 are each independently selected from CH or N; each X8 is independently selected from the group consisting of O, S, or NH; R 17is selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, halogenated C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, halogenated C1-C5 alkyl, or straight or branched C1-C5 alkyl, where optionally, halogen can be, for example, F, Cl, Br, or I. Optionally, C1-C6 alkoxy can include, but is not limited to, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentoxy, isopentyloxy, n-hexyloxy, 3,3-dimethylbutoxy, 2-ethylbutoxy, etc. Optionally, halogenated C1-C6 alkoxy can be, for example, trifluoromethoxy, etc. Optionally substituted or unsubstituted amino may include amino, N-methylamino, N-ethylamino, N-phenylamino, N,N-dimethylamino, N,N-diethylamino, etc. Optionally substituted or unsubstituted silyl may be, for example, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, vinyldimethylsilyl, propyldimethylsilyl, triphenylsilyl, diphenylsilyl, phenylsilyl, etc. Optionally substituted or unsubstituted boryl may include, for example, trimethylboryl, triethylboryl, tert-butyldimethylboryl, triphenylboryl, phenylboryl, etc. Optionally, straight or branched C1-C5 alkyl includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methyl-butyl, 1-ethyl-butyl, pentyl, n-pentyl, isopentyl, neopentyl, and tert-pentyl, and said straight or branched C1-C5 alkyl is optionally substituted, where the substituent is optionally one or more substituents selected from the group consisting of D (i.e., deuterium), halogen, hydroxy, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl (e.g., a 4- to 8-membered heterocycle), or any combination thereof.

[0110] In embodiment 59), compounds of formula I according to any one of embodiments 1 to 58) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a is selected from the group consisting of deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, halogenated alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted straight or branched chain alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0111] In embodiment 60), compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a is deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, halogenated C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched C1-C5 alkyl, substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted C5-C 15 It is selected from the group consisting of aryl, or substituted or unsubstituted 5- to 15-membered heteroaryl.

[0112] In embodiment 61), compounds of formula I according to embodiment 59) or 60) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a is deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, trifluoromethoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched C1-C5 alkyl, substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted C5-C 15It is selected from the group consisting of aryl, or substituted or unsubstituted 5- to 15-membered heteroaryl.

[0113] In embodiment 62), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is deuterium.

[0114] In embodiment 63), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a halogen, optionally wherein the halogen is F, Cl, Br, or I.

[0115] In embodiment 64), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is nitro.

[0116] In embodiment 65), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is cyano.

[0117] In embodiment 66), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is an amino.

[0118] In embodiment 67), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is hydroxy.

[0119] In embodiment 68), with respect to compounds of formula I according to embodiment 59), or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is mercapto.

[0120] In embodiment 69), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is alkoxy. a is an alkoxy, the alkoxy is a C1-C6 alkoxy. The C1-C6 alkoxy may include, but is not limited to, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentoxy, isopentyloxy, n-hexyloxy, 3,3-dimethylbutoxy, 2-ethylbutoxy, etc.

[0121] In embodiment 70), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a halogenated alkoxy. a is a halogenated alkoxy, wherein said halogenated alkoxy is a halogenated C1-C6 alkoxy; further optionally, said halogenated C1-C6 alkoxy is trifluoromethoxy, etc.

[0122] In embodiment 71), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a substituted or unsubstituted amino. Optionally substituted or unsubstituted amino includes amino, N-methylamino, N-ethylamino, N-phenylamino, N,N-dimethylamino, N,N-diethylamino, and the like.

[0123] In embodiment 72), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a substituted or unsubstituted silyl. Optionally, the substituted or unsubstituted silyl is specifically trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, vinyldimethylsilyl, propyldimethylsilyl, triphenylsilyl, diphenylsilyl, phenylsilyl, and the like.

[0124] In embodiment 73), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a substituted or unsubstituted boryl. Optionally, the substituted or unsubstituted boryl is specifically trimethylboryl, triethylboryl, tert-butyldimethylboryl, triphenylboryl, phenylboryl, and the like.

[0125] In embodiment 74), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a substituted or unsubstituted straight or branched chain alkyl. Optionally, the number of carbon atoms may be, for example, C-C 30 , C1-C 25 , C1-C 20 , C1-C 15 , C1-C 10 , C1-C5, C1-C3, etc. Preferably, it is a straight or branched C1-C 10 and optionally straight or branched C-C alkyl. 10 Alkyl includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methylbutyl, 1-ethylbutyl, pentyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 4-methyl-2-pentyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl, n-heptyl, 1-methylhexyl, cyclopentylmethyl, cyclohexylmethyl, octyl, n-octyl, tert-octyl, 1-methylheptyl, 2-ethylhexyl, 2-propylpentyl, n-nonyl, 2,2-dimethylheptyl, 1-ethylpropyl, 1,1-dimethylpropyl, isohexyl, 4-methylhexyl, 5-methylhexyl, etc. Optionally, straight or branched C-C 10Alkyl includes, but is not limited to, methyl, ethyl, propyl, etc. Here, the alkyl is optionally substituted, and the substituent may be, for example, one or more substituents selected from the group consisting of deuterium, halogen, cyano, nitro, hydroxy, mercapto, carbonyl, ester group, imido group, amino, phosphine oxide group, alkoxy, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, deuterated alkyl, alkyl halide, amino-substituted alkylene, alkyl-NHC(O)-, alkyl-C(O)NH-, cycloalkyl, deuterated cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, acenaphthenyl, oxo group, or any combination thereof. The substituent is preferably D (i.e., deuterium), halogen, hydroxy, cyano, C 1-3 Alkyl, C 1-3 It is one or more substituents selected from the group consisting of alkoxy, trifluoromethyl, heterocyclyl (for example, a 4- to 8-membered heterocycle), or any combination thereof.

[0126] In embodiment 75), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a substituted or unsubstituted cycloalkyl. a When is a substituted or unsubstituted cycloalkyl, it is preferably 3 to 20 carbon atoms (i.e., C 3-20 cycloalkyl), or 3 to 15 carbon atoms (i.e., C 3-15 cycloalkyl), 3 to 12 carbon atoms (i.e., C 3-12 cycloalkyl), or 3 to 11 carbon atoms (i.e., C 3-11 cycloalkyl), or 3 to 10 carbon atoms (i.e., C 3-10 cycloalkyl), or 3 to 8 carbon atoms (i.e., C 3-8cycloalkyl), or 3 to 7 carbon atoms (i.e., C 3-7 cycloalkyl), or 3 to 6 carbon atoms (i.e., C 3-6 Preferably, R1 is a substituted or unsubstituted C3-C 15 cycloalkyl. Optionally, C3-C 15 Cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl or C5-C 15 Spirocycloalkyl or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl, and the like. Optionally, C-C 15Cycloalkyl includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and the like. wherein the cycloalkyl is optionally substituted, and the substituent is optionally one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents selected from the group consisting of trifluoromethyl, mercapto, hydroxy, amino, halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl, deuterium, nitro, carbonyl, ester group, imido group, amino, phosphine oxide group, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, deuterated alkyl, amino-substituted alkylene, alkyl-NHC(O)—, alkyl-C(O)NH—, cycloalkyl, deuterated cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, acenaphthenyl, oxo group, or any combination thereof. The substituents are preferably one or more substituents selected from the group consisting of trifluoromethyl, mercapto, hydroxy, amino, halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl, or any combination thereof.

[0127] In embodiment 76), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a substituted or unsubstituted heterocyclyl. ais a substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is a substituted or unsubstituted 4- to 30-membered heterocyclyl, 4- to 25-membered heterocyclyl, 4- to 20-membered heterocyclyl, 4- to 15-membered heterocyclyl, 4- to 10-membered heterocyclyl, 10- to 15-membered heterocyclyl, 5- to 15-membered heterocyclyl, or 7- to 15-membered heterocyclyl, etc. Optionally, the heterocyclyl contains 1 to 3 heteroatoms, or 1 to 2 heteroatoms, or 1 heteroatom, etc. Each heteroatom is independently selected from the group consisting of O, N, S, etc. Further optionally, the heterocyclyl is azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, dioxacyclohexenyl, azacycloheptanyl, diazacycloheptanyl (e.g., 1,4-diazacycloheptanyl, 4,5-diazacycloheptanyl, or 1,3-diazacycloheptanyl), azacycloheptanyl, cyclohex ...

[0033] Cis-7-azabicyclo[3.3.0]octyl, and the like.

[0034] Cis-7-azabicyclo[3.3.0]octyl, and the like.

[0035] Cis-7-azabicyclo[3.3.0]octyl, and the like.

[0036] Cis-7-azabicyclo[3.3.0]octyl, and the like.

[0037] Cis-7-azabicyclo[3.3.0]octyl, and the like.

[0038] Cis-7-azabicyclo[3.3.0]octyl, and the like. [0039 ...The heterocyclyl may be unsubstituted or substituted (e.g., mono-, di-, tri- or polysubstituted) as clearly defined, where the substituents are optionally selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, carbonyl, ester, imido, phosphine oxide, trifluoromethoxy, oxo, optionally deuterated 1-C6 alkyl, halogenated C1-C6 alkyl, optionally deuterated 3-6 cycloalkyl, optionally deuterated 1-C6 alkoxy, C1-4 alkyl-NH-, NH2-C1-6 alkylene, C1-4 alkyl-NHC(O)-, C1-4 alkyl-C(O)NH-, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino, heteroaryl, acenaphthenyl, and any combination thereof. Preferably, the substituents are selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo group, optionally deuterated 1-C6 alkyl, halogenated C1-C6 alkyl, optionally deuterated 3-6 cycloalkyl, optionally deuterated 1-C6 alkoxy, C1-4 alkyl-NH-, NH2-C1-6 alkylene, C1-4 alkyl-NHC(O)-, C1-4 alkyl-C(O)NH- and any combination thereof.

[0128] In embodiment 77), with respect to compounds of formula I according to embodiment 59) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a substituted or unsubstituted aryl. Optionally, the substituted or unsubstituted aryl is a substituted or unsubstituted C5- 30 Optionally, substituted or unsubstituted C5- 30 The aryl in the formula (I) is a substituted or unsubstituted C5- 25 , C5- 20 , or C5- 15 Optionally, C5- 30The aryl may be a monocyclic aryl or a polycyclic aryl. In some embodiments, monocyclic aryls include, but are not limited to, phenyl, biphenyl, terphenyl, quaterphenyl, and quinquephenyl. Polycyclic aryls include, but are not limited to, naphthyl, anthryl, phenanthryl, pyrenyl, perylenyl, and fluorenyl. Fluorenyl may be substituted, such as 9,9'-dimethylfluorenyl and 9,9'-diphenylfluorenyl. Two substituents may be bonded to each other to form a spiro ring structure, such as 9,9'-spirobifluorenyl. The aryl may be optionally substituted. Substituted aryl refers to an aryl substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent (e.g., an aryl mono-, di-, or tri-substituted with a substituent), where the substituents are optionally selected from the group consisting of, for example, optionally deuterated C1-C6 alkyl, deuterated C3-6 cycloalkyl, deuterium, hydroxy, amino, mercapto, halogen, cyano, nitro, carbonyl, ester group, imido group, phosphine oxide group, trifluoromethoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)—, C1-C4 alkyl-C(O)NH—, alkyl, cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, acenaphthenyl, and any combination thereof. Preferably, the substituents are selected from the group consisting of deuterated C1-C6 alkyl, deuterated C3-6 cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0129] In embodiment 78), with respect to compounds of formula I according to embodiment 59), or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a substituted or unsubstituted heteroaryl. ais a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5- to 30-membered heteroaryl. Optionally, the substituted or unsubstituted 5- to 30-membered heteroaryl is a substituted or unsubstituted 5- to 15-membered, 5- to 12-membered, 5- to 11-membered, 5- to 10-membered, 5- to 9-membered, 5- to 8-membered, 5- to 7-membered, 5- to 6-membered, 6- to 15-membered, or 6- to 9-membered heteroaryl. Optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, cinnolinyl, naphthyridinyl, acridinyl, xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyrazolopyridyl, pyrazolopyrimidinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyrazinyl, Examples of heteroaryl include, but are not limited to, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, isobenzofuranyl, dibenzothienyl, dibenzofuranyl, indazolyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, pyrrolopyridinyl, pyrrolothiazolyl, imidazothiazolyl, pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, and naphthothianaphthenyl, etc., wherein the heteroaryl may be substituted or unsubstituted.Substituted heteroaryl refers to heteroaryl substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent, wherein the substituent is optionally selected from the group consisting of C-C alkyl, C-C cycloalkyl, hydroxy, amino, mercapto, halogen, deuterium, nitro, carbonyl, an ester group, an imido group, a phosphine oxide group, trifluoromethoxy, C-C alkoxy, C-C alkylamino, halogenated C-C alkyl, amino-substituted C-C alkylene, C-C alkyl-NHC(O)—, C-C alkyl-C(O)NH—, cyano, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, acenaphthenyl, or any combination thereof. Preferably, the substituents are optionally selected from the group consisting of C1-C3 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen, C1-C3 alkoxy, C1-C3 alkylamino, halogenated C1-C3 alkyl, amino-substituted C1-C3 alkylene, C1-C3 alkyl-NHC(O)-, C1-C3 alkyl-C(O)NH-, cyano, or any combination thereof.

[0130] In embodiment 79), compounds of formula I according to any one of embodiments 1 to 78) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, alkoxy halide, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, and substituted or unsubstituted straight or branched chain alkyl.

[0131] In embodiment 80), compounds of formula I according to any one of embodiments 1-78) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R b1 , Rb2 , R b3 , R b4 , R b5 are each independently selected from the group consisting of hydrogen, deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, halogenated C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, or substituted or unsubstituted straight or branched chain C1-C5 alkyl.

[0132] In embodiment 81), compounds of formula I according to any one of embodiments 1-78) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from the group consisting of hydrogen, deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, trifluoromethoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, or substituted or unsubstituted straight or branched chain C1-C5 alkyl.

[0133] In embodiment 82), with respect to a compound of formula I according to any one of embodiments 1 to 78, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, R b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from hydrogen.

[0134] In embodiment 83), with respect to compounds of formula I according to embodiment 81) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from deuterium.

[0135] In embodiment 84), with respect to compounds of formula I according to embodiment 81) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from halogen. b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from halogen, the halogen is F, Cl, Br, or I.

[0136] In embodiment 85), with respect to compounds of formula I according to embodiment 81) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from nitro.

[0137] In embodiment 86), with respect to compounds of formula I according to embodiment 81), or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from cyano.

[0138] In embodiment 87), with respect to compounds of formula I according to embodiment 81) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from amino.

[0139] In embodiment 88), with respect to compounds of formula I according to embodiment 81), or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R b1 , R b2 , R b3, R b4 , R b5 are each independently selected from hydroxy.

[0140] In embodiment 89), with respect to compounds of formula I according to embodiment 81) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from mercapto.

[0141] In embodiment 90), with respect to compounds of formula I according to embodiment 81) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from alkoxy. b1 , R b2 , R b3 , R b4 , R b5 is independently selected from alkoxy, the alkoxy is C1-C6 alkoxy. Further optionally, alkoxy may include, but is not limited to, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentoxy, isopentyloxy, n-hexyloxy, 3,3-dimethylbutoxy, 2-ethylbutoxy, etc.

[0142] In embodiment 91), with respect to compounds of formula I according to embodiment 81) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from halogenated alkoxy. b1 , R b2 , R b3 , Rb4 , R b5 are each independently selected from halogenated alkoxy, the halogenated alkoxy is halogenated C1-C6 alkoxy. Further, the halogenated C1-C6 alkoxy may be trifluoromethoxy or the like.

[0143] In embodiment 92), with respect to compounds of formula I according to embodiment 81) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from the group consisting of substituted or unsubstituted amino, including, but not limited to, amino, N-methylamino, N-ethylamino, N-phenylamino, N,N-dimethylamino, N,N-diethylamino, and the like.

[0144] In embodiment 93), with respect to compounds of formula I according to embodiment 81) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from the group consisting of substituted or unsubstituted silyl, where the optionally substituted or unsubstituted silyl is specifically trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, vinyldimethylsilyl, propyldimethylsilyl, triphenylsilyl, diphenylsilyl, phenylsilyl, and the like.

[0145] In embodiment 94), with respect to compounds of formula I according to embodiment 81) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R b1 , R b2 , R b3 , R b4 , R b5are each independently selected from the group consisting of substituted or unsubstituted boryl, where the optionally substituted or unsubstituted boryl is specifically trimethylboryl, triethylboryl, tert-butyldimethylboryl, triphenylboryl, phenylboryl, and the like.

[0146] In embodiment 95), with respect to compounds of formula I according to embodiment 81) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R b1 , R b2 , R b3 , R b4 , R b5 are each independently selected from the group consisting of substituted or unsubstituted straight or branched chain alkyl. Optionally, the number of carbon atoms may be, for example, C-C 30 , C1-C 25 , C1-C 20 , C1-C 15 , C1-C 10 , C1-C5 or C1-C3, etc. Preferably, it is a straight or branched C1-C 10 and optionally straight or branched C-C alkyl. 10 Alkyl includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methylbutyl, 1-ethylbutyl, pentyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 4-methyl-2-pentyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl, n-heptyl, 1-methylhexyl, cyclopentylmethyl, cyclohexylmethyl, octyl, n-octyl, tert-octyl, 1-methylheptyl, 2-ethylhexyl, 2-propylpentyl, n-nonyl, 2,2-dimethylheptyl, 1-ethylpropyl, 1,1-dimethylpropyl, isohexyl, 4-methylhexyl, and 5-methylhexyl, and the like. 10Alkyl includes, but is not limited to, methyl, ethyl, and propyl. The alkyl is optionally substituted, and the substituents include, for example, deuterium, halogen, cyano, nitro, hydroxy, mercapto, carbonyl, ester group, imide group, amino, phosphine oxide group, alkoxy, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, deuterated alkyl, alkyl halide, amino-substituted alkylene, alkyl-NHC(O)-, alkyl-C(O)NH-, cycloalkyl, deuterated cycloalkyl, and alkyl. The substituents may be selected from the group consisting of alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, acenaphthenyl, oxo group, or any combination thereof, and are preferably one or more substituents selected from the group consisting of D (i.e., deuterium), halogen, hydroxy, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl (e.g., 4- to 8-membered heterocycle), or any combination thereof.

[0147] In embodiment 96), with respect to a compound of formula I according to any one of embodiments 1 to 95), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, n is an integer of 0, 1, 2, or 3, and when n is an integer of 2 or 3, each R a In some embodiments, n represents an integer of 0, 1, or 2.

[0148] In embodiment 97), with respect to a compound of formula I according to any one of embodiments 1 to 96), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, R a1 For better representation, it is further represented as -L2-L3. The chemical structure of the compound is represented by Formula I-1 or Formula I-2. [ka] Formula I-1 [ka] Formula I-2 In Formula I-1 or Formula I-2, X, L1, X1 to X2, R a , R b1 , R b2 , R b3 , R b4 , R b5 wherein n is as defined for compounds of formula I according to any one of embodiments 1) to 96) above; L2 is a substituted or unsubstituted C5-C 30 Arylene, substituted or unsubstituted 5- to 30-membered heteroarylene, substituted or unsubstituted C3-C 30 cycloalkylene, or substituted or unsubstituted 4- to 30-membered heterocyclylene, or L2 is absent; L3 is a substituted or unsubstituted C5-C 30 Aryl, substituted or unsubstituted 5-30 membered heteroaryl, substituted or unsubstituted C3-C 30 cycloalkyl, or substituted or unsubstituted 4- to 30-membered heterocyclyl; R a2 is a substituted or unsubstituted C5-C 30 Aryl, substituted or unsubstituted 5-30 membered heteroaryl, substituted or unsubstituted C3-C 30 cycloalkyl, or substituted or unsubstituted 4- to 30-membered heterocyclyl; wherein in Formula I-1, X3 is selected from CR1 or N, and in Formula I-2, X3 is selected from the group consisting of CR1, N, or CO, where R1 is as defined in the compounds of Formula I according to any one of embodiments 1) to 96).

[0149] In embodiment 98), with respect to the compound of formula I-1 or I-2 according to embodiment 97), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, L2 is selected from the group consisting of substituted or unsubstituted 5- to 20-membered heteroarylene (e.g., substituted or unsubstituted 5- to 15-membered heteroarylene); preferably, the heteroarylene is selected from the group consisting of pyridylene, pyrrolylene, pyrimidinylene, pyridazinylene, furanylene, thienylene, imidazolylene, pyrazolylene, oxazolylene, isopropyl, ... xazolylene, thiazolylene, isothiazolylene, triazolylene, oxadiazolylene, thiadiazolylene, tetrazolylene, pyranylene, thiopyranylene, pyrazinylene, pyridazinylene, thiazinylene, triazinylene, tetrazinylene, quinolinylene, isoquinolinylene, quinazolinylene, quinoxalinylene, cinnolinylene, naphthyridinylene, acridinylene, xanthenylene, phenanthridinylene, diazanaphthylene, triazaindenylene, indolylene, Indolinylene, indolizinylene, phthalazinylene, pyrazolopyridylene, pyrazolopyrimidinylene, pyridopyrimidinylene, pyridopyrazinylene, pyrazinopyrazinylene, benzothiazolylene, benzoxazolylene, benzimidazolylene, benzothienylene, benzofuranylene, isobenzofuranylene, dibenzothienylene, dibenzofuranylene, indazolylene, carbazolylene, benzocarbazolylene, dibenzocarbazolylene, indolocarbazolylene, indene and n-, 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12-, 13-, 14-, 15-, 16-, 17-, 18-, 19-, 20-, 21-, 22-, 23-, 24-, 25-, 26-, 27-, 28-, 29-, 30-, 31-, 32-, 33-, 34-, 35-, 36-, 37-, 38-, 39-, 40-, 41-, 42-, 43-, 44-, 45-, 46-, 47-, 48-, 49-, 50-, 51-, 52-, 53-, 54-, 55-, 56-, 57-, 58-, 59-, 60-, 61-, 62-, 63-, 64-, 65-, 66-, 67-, 68-, 69-, 70-, 71-, 72-, 73-, 74-, 75-, 76-, 77-, 78-, 79-, 80-, 81-, 82-, 83-, 84-, 85-, 86-, 87-, 88-, 89-, 90-, 91-, 92-, 93-, 94-, 95-, 96-, 97-, 98-, 99-, 100-, 101-, 102-, 103-,Substituted heteroarylene refers to a heteroarylene substituted one or more times (e.g., 1 to 4, 1 to 3, or 1 to 2 times) with substituents, where the substituents are optionally selected from the group consisting of C-C alkyl, C-C cycloalkyl, hydroxy, amino, mercapto, halogen, deuterium, nitro, carbonyl, an ester group, an imido group, a phosphine oxide group, trifluoromethoxy, C-C alkoxy, C-C alkylamino, halogenated C-C alkyl, amino-substituted C-C alkylene, C-C alkyl-NHC(O)—, C-C alkyl-C(O)NH—, cyano, alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino group, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, acenaphthenyl, or any combination thereof. Preferably, the substituents are optionally selected from the group consisting of C1-C3 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen, C1-C3 alkoxy, C1-C3 alkylamino, halogenated C1-C3 alkyl, amino-substituted C1-C3 alkylene, C1-C3 alkyl-NHC(O)-, C1-C3 alkyl-C(O)NH-, cyano, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or any combination thereof. Furthermore, when L2 is substituted heteroarylene and the heteroarylene substituent is substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl may be substituted or unsubstituted C3-C6 cycloalkyl. 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C 10cycloalkyl and substituted or unsubstituted C3-C6 cycloalkyl); optionally, cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl, C5-C 15 Spirocycloalkyl, or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged Cycloalkyl, C5-C 15 Bridged cycloalkyl, or C7-C 15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy,

[0033] Furthermore, when L2 is a substituted heteroarylene and the substituent of the heteroarylene is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl may be selected from the group consisting of substituted or unsubstituted C5-C6 alkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. 20 Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl and substituted or unsubstituted C5-C 10aryl, etc.); optionally, the aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; the aryl is an optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1). For example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Furthermore, when L2 is a substituted heteroarylene and the heteroarylene substituent is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is selected from the group consisting of a substituted or unsubstituted 5- to 25-membered heteroaryl (e.g., a substituted or unsubstituted 5- to 20-membered heteroaryl, a substituted or unsubstituted 5- to 15-membered heteroaryl, or a substituted or unsubstituted 5- to 10-membered heteroaryl);Optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinyl, selected from the group consisting of dinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1). For example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Furthermore, when L2 is a substituted heteroarylene and the heteroarylene substituent is a substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is selected from the group consisting of substituted or unsubstituted 4-20 membered heterocyclyl (e.g., substituted or unsubstituted 4-15 membered heterocyclyl, substituted or unsubstituted 4-10 membered heterocyclyl, or substituted or unsubstituted 4-8 membered heterocyclyl, etc.); optionally, the heterocyclyl is selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, dioxacyclohexenyl, azacyclohepta; nyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl, 5- to 15-membered bridged heterocyclyl, or 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (e.g., 4- to 15-membered spiroheterocyclyl, 5- to 15-membered spiroheterocyclyl, or 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); heterocyclyl is optionally substituted heterocyclyl; The number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0150] In embodiment 99), the compound of formula I-1, formula I-2 or a salt, enantiomer, stereoisomer, polymorph or solvate thereof according to embodiment 97), wherein L2 is a substituted or unsubstituted C3-C 20 Cycloalkylene (e.g., substituted or unsubstituted C3-C 15 Preferably, L2 is selected from the group consisting of cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decalinylene, octahydrocyclopentalenylene, octahydro-1H-indenylene, spirocycloalkylene (e.g., C3-C 15 Spirocycloalkylene, C5-C 15 Spirocycloalkylene, or C7-C 15spirocycloalkylene, such as spiro[3.3]heptylene, spiro[2.5]octylene, spiro[3.5]nonylene, spiro[4.4]nonylene, spiro[4.5]decylene, or spiro[5.5]undecylene), or bridged cycloalkylene (e.g., C-C 15 Bridged Cycloalkylene, C5-C 15 Bridged cycloalkylene or C7-C 15and bridged cycloalkylenes, such as adamantanylene, noradamantanylene, bornylene, biscyclo[2.2.1]heptylene, 2-oxobiscyclo[2.2.1]heptylene, or biscyclo[2.2.1]heptenylene), wherein the "cycloalkylene" is optionally substituted, and the substituents are preferably trifluoromethyl, mercapto, hydroxy, amino, halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl, deuterium, nitro, carbonyl, ester group, imido group, phosphine oxide group, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, deuterated alkyl, amino-substituted alkylene, aryl and one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents selected from the group consisting of alkyl-NHC(O)-, alkyl-C(O)NH-, substituted or unsubstituted cycloalkyl, deuterated cycloalkyl, alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, acenaphthenyl, oxo group, or any combination thereof. Furthermore, the substituents are preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents selected from the group consisting of trifluoromethyl, mercapto, hydroxy, amino, halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or any combination thereof. Furthermore, when L2 is substituted cycloalkylene and the cycloalkylene substituent is substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl is preferably substituted or unsubstituted C3-C 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C 10cycloalkyl, substituted or unsubstituted C3-C6 cycloalkyl, etc.; optionally, the cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl, C5-C 15 Spirocycloalkyl, or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged Cycloalkyl, C5-C 15 Bridged cycloalkyl, or C7-C 15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy,

[0033] In addition, when L2 is a substituted cycloalkylene and the substituent of the cycloalkylene is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl may be selected from the group consisting of substituted or unsubstituted C5-C6 alkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. 20 Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl and substituted or unsubstituted C5-C10aryl, etc.); optionally, the aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; the aryl is an optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1). For example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Furthermore, when L2 is a substituted cycloalkylene and the cycloalkylene substituent is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is selected from the group consisting of substituted or unsubstituted 5- to 25-membered heteroaryl (e.g., substituted or unsubstituted 5- to 20-membered heteroaryl, substituted or unsubstituted 5- to 15-membered heteroaryl, or substituted or unsubstituted 5- to 10-membered heteroaryl);Optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinyl, selected from the group consisting of dinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1). For example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Furthermore, when L2 is a substituted cycloalkylene and the cycloalkylene substituent is a substituted or unsubstituted heterocyclyl, the heterocyclyl is selected from the group consisting of substituted or unsubstituted 4- to 20-membered heterocyclyl (e.g., substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted 4- to 10-membered heterocyclyl, or substituted or unsubstituted 4- to 8-membered heterocyclyl, etc.); optionally, the heterocyclyl is selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxa cyclohexyl, dioxacyclohexenyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl, 5- to 15-membered bridged heterocyclyl, or 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (e.g., 4- to 15-membered spiroheterocyclyl, 5- to 15-membered spiroheterocyclyl, or 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); heterocyclyl is an optionally substituted heterocyclyl, and the number of substituents is preferably one or more; The number of substituents is several (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0151] In embodiment 100), the compound of formula I-1 or I-2 or a salt, enantiomer, stereoisomer, polymorph or solvate thereof according to embodiment 97), wherein L2 is a substituted or unsubstituted C5-C 20 Arylene (e.g., substituted or unsubstituted C5-C 15Preferably, L2 is selected from the group consisting of phenylene, biphenylene, terphenylene, naphthylene, anthrylene, phenanthrylene, fluorenylene, and 9,9'-dimethylfluorenylene. The arylene is an optionally substituted arylene. Substituted arylene refers to an arylene substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent, for example, the arylene is mono-, di-, or tri-substituted with a substituent, wherein the substituent is optionally selected from, for example, deuterated C1-C6 alkyl, deuterated C3-C6 cycloalkyl, deuterium, hydroxy, amino, mercapto, halogen, cyano, nitro, carbonyl, an ester group, an imide group, a phosphine oxide group, trifluoromethoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, and the like. and any combination thereof. Preferably, the substituents are selected from the group consisting of deuterated C1-C6 alkyl, deuterated C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, and any combination thereof. Furthermore, when L2 is a substituted arylene and the arylene substituent is substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl can be substituted or unsubstituted C3-C 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15Cycloalkyl, substituted or unsubstituted C3-C 10 cycloalkyl and substituted or unsubstituted C3-C6 cycloalkyl); optionally, cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl, C5-C 15 Spirocycloalkyl, or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged Cycloalkyl, C5-C 15 Bridged cycloalkyl, or C7-C 15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy,

[0033] In addition, when L2 is a substituted arylene and the substituent of the arylene is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl may be selected from the group consisting of substituted or unsubstituted C5-C6 alkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. 20 Aryl (e.g., substituted or unsubstituted C5-C 15Aryl and substituted or unsubstituted C5-C 10aryl, etc.) (optionally, aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; aryl is optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof). Furthermore, when L2 is a substituted arylene and the arylene substituent is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is selected from the group consisting of substituted or unsubstituted 5- to 25-membered heteroaryl (e.g., substituted or unsubstituted 5- to 20-membered heteroaryl, substituted or unsubstituted 5- to 15-membered heteroaryl, and substituted or unsubstituted 5- to 10-membered heteroaryl);Optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinyl, selected from the group consisting of dinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1). For example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Furthermore, when L2 is a substituted arylene and the arylene substituent is a substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is selected from the group consisting of substituted or unsubstituted 4- to 20-membered heterocyclyl (e.g., substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted 4- to 10-membered heterocyclyl, and substituted or unsubstituted 4- to 8-membered heterocyclyl, etc.); optionally, the heterocyclyl is selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, aryl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, dioxacyclohexenyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl, 5- to 15-membered bridged heterocyclyl, or 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (e.g., 4- to 15-membered spiroheterocyclyl, 5- to 15-membered spiroheterocyclyl, or 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl);The heterocyclyl is an optionally substituted heterocyclyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and examples of the substituents include C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-; It is selected from the group consisting of C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0152] In embodiment 101), with respect to the compound of formula I-1 or I-2 according to embodiment 97), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, L2 is selected from the group consisting of substituted or unsubstituted 4- to 20-membered heterocyclylene (e.g., substituted or unsubstituted 4- to 15-membered heterocyclylene); preferably, L2 is selected from the group consisting of azetidinylene, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, dihydropyranylene, tetrahydrothienylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, dioxacyclopent ...

[0049] azacyclohexylene, dioxacyclohexenylene, azacycloheptanylene, diazacycloheptanylene, diazacyclooctylene, bridged heterocyclylene (e.g., 4- to 15-membered bridged heterocyclylene, 5- to 15-membered bridged heterocyclylene, or 7- to 15-membered bridged heterocyclylene, such as azabicyclohexylene, azabicycloheptanylene, diazabicycloheptanylene, azabicyclooctylene), or spiroheterocyclylene (e.g., 4- to 15-membered spiroheterocyclylene, 5- to 15-membered spiroheterocyclylene, or 7- to 15-membered spiroheterocyclylene, such as 3-azaspiro[5.5]undecanylene or 7-azaspiro[3.5]nonanylene).The heterocyclylene may be unsubstituted or substituted (e.g., mono-, di-, tri-, or poly-substituted) as clearly defined, where the substituents are optionally deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, carbonyl, ester group, imido group, phosphine oxide group, trifluoromethoxy, oxo group, optionally deuterated 1-C6 alkyl, halogenated C1-C6 alkyl, optionally deuterated 3-C6 cycloalkyl, optionally deuterated 1- and any combination thereof. Preferably, the substituents are selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated 1-C6 alkyl, halogenated C1-C6 alkyl, optionally deuterated 3-C6 cycloalkyl, optionally deuterated 1-C6 alkoxy, C1-C4 alkyl-NH-, NH2-C1-6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, and any combination thereof. Furthermore, when L2 is substituted heterocyclylene and the heterocyclylene substituent is substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl may be substituted or unsubstituted C3-C6 alkyl. 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C 10cycloalkyl, and substituted or unsubstituted C3-C6 cycloalkyl; optionally, cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl, C5-C 15 Spirocycloalkyl, or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged Cycloalkyl, C5-C 15 Bridged cycloalkyl, or C7-C 15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy,

[0033] Furthermore, when L2 is a substituted heterocyclylene and the substituent of the heterocyclylene is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl may be selected from the group consisting of substituted or unsubstituted C5-C6 alkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. 20 Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl, substituted or unsubstituted C5-C 10aryl, etc.); optionally, the aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; the aryl is an optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1). For example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Furthermore, when L2 is a substituted heterocyclylene and the heterocyclylene substituent is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is selected from the group consisting of a substituted or unsubstituted 5- to 25-membered heteroaryl (e.g., a substituted or unsubstituted 5- to 20-membered heteroaryl, a substituted or unsubstituted 5- to 15-membered heteroaryl, or a substituted or unsubstituted 5- to 10-membered heteroaryl);Optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, bis(triazinyl), tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, selected from the group consisting of pyrazinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1). For example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. When L2 is substituted heterocyclylene and the heterocyclylene substituent is substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is selected from the group consisting of substituted or unsubstituted 4- to 20-membered heterocyclyl (e.g., substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted 4- to 10-membered heterocyclyl, or substituted or unsubstituted 4- to 8-membered heterocyclyl, etc.); optionally, the heterocyclyl is selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetra ... thiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, dioxacyclohexenyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl, 5- to 15-membered bridged heterocyclyl, or 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (e.g., 4- to 15-membered spiroheterocyclyl, 5- to 15-membered spiroheterocyclyl, or; is selected from the group consisting of 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl; the heterocyclyl is an optionally substituted heterocyclyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1). For example, the substituents are selected from the group consisting of C-C alkyl, C-C cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo, C-C alkoxy, deuterated C-C alkoxy, C-C alkylamino, halogenated C-C alkyl, halogenated C-C cycloalkyl, amino-substituted C-C alkylene, C-C alkyl-NHC(O)—, C-C alkyl-C(O)NH—, and any combination thereof.

[0153] In embodiment 102), for compounds of formula I-1 and I-2 or salts, enantiomers, stereoisomers, polymorphs or solvates thereof according to embodiment 97), L2 is absent.

[0154] In embodiment 103), with respect to compounds of formula I-1 and I-2 according to any one of embodiments 97) to 102) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, L2 is [ka] selected from the group consisting of: where: X4 is selected from the group consisting of O, S, or NH; X5 is O, S, or NR 16 where R 16 represents hydrogen or C1-C3 alkyl; R2, R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 , R 13 , R 14 , R 15are each independently selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, halogenated C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, halogenated C1-C5 alkyl, or straight or branched C1-C5 alkyl. Optionally, halogen can be, for example, F, Cl, Br, and I. Optionally, C1-C6 alkoxy can include, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentoxy, isopentyloxy, n-hexyloxy, 3,3-dimethylbutoxy, and 2-ethylbutoxy. Optionally, halogenated C1-C6 alkoxy can be, for example, trifluoromethoxy. Optionally, substituted or unsubstituted amino includes amino, N-methylamino, N-ethylamino, N-phenylamino, N,N-dimethylamino, N,N-diethylamino, etc. Optionally, substituted or unsubstituted silyl can be, for example, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, vinyldimethylsilyl, propyldimethylsilyl, triphenylsilyl, diphenylsilyl, phenylsilyl, etc. Optionally, substituted or unsubstituted boryl can include, for example, trimethylboryl, triethylboryl, tert-butyldimethylboryl, triphenylboryl, phenylboryl, etc. Optionally, the straight or branched chain C1-C5 alkyl includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methyl-butyl, 1-ethyl-butyl, pentyl, n-pentyl, isopentyl, neopentyl, and tert-pentyl, and the straight or branched chain C1-C5 alkyl is optionally substituted, where the substituent is optionally one or more substituents selected from the group consisting of D (i.e., deuterium), halogen, hydroxy, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl (e.g., a 4- to 8-membered heterocycle), or any combination thereof.

[0155] In embodiment 104), with respect to the compounds of formula I-1 and I-2 according to any one of embodiments 97) to 103), or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, L3 is a substituted or unsubstituted C5-C 30 Aryl, substituted or unsubstituted 5-30 membered heteroaryl, substituted or unsubstituted C3-C 30 It is selected from the group consisting of cycloalkyl, or substituted or unsubstituted 4- to 30-membered heterocyclyl.

[0156] In embodiment 105), the compounds of formula I-1 and I-2 according to embodiment 104) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein L3 is a substituted or unsubstituted C5-C 20 Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl, substituted or unsubstituted C5-C 10aryl, etc. Preferably, L3 is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, and 9,9'-dimethylfluorenyl. The aryl may be a monocyclic aryl or a polycyclic aryl. In some embodiments, the monocyclic aryl includes, but is not limited to, phenyl, biphenyl, terphenyl, quaterphenyl, quinquephenyl, etc. The polycyclic aryl includes, but is not limited to, naphthyl, anthryl, phenanthryl, pyrenyl, perylenyl, fluorenyl, etc. The fluorenyl may be substituted, for example, 9,9'-dimethylfluorenyl, 9,9'-diphenylfluorenyl, etc. Preferably, L3 is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, and 9,9'-dimethylfluorenyl. Furthermore, two substituents may be bonded to each other to form a spiro ring structure, for example, 9,9'-spirobifluorenyl, etc. The aryl is an optionally substituted aryl. Substituted aryl refers to an aryl substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent (e.g., an aryl mono-, di-, or tri-substituted with a substituent), where the substituent is optionally selected from, for example, deuterated C1-C6 alkyl, deuterated C3-C6 cycloalkyl, deuterium, hydroxy, amino, mercapto, halogen, cyano, nitro, carbonyl, an ester group, an imide group, a phosphine oxide group, trifluoromethoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, and the like. and any combination thereof.Preferably, the substituents are selected from the group consisting of deuterated C1-C6 alkyl, deuterated C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen, cyano, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, and any combination thereof. Furthermore, when L3 is substituted aryl and the aryl substituent is substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl may be substituted or unsubstituted C3-C4 alkyl. 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C 10 cycloalkyl, substituted or unsubstituted C3-C6 cycloalkyl, etc.; optionally, cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl, C5-C 15 Spirocycloalkyl, or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged Cycloalkyl, C5-C 15 Bridged cycloalkyl, or C7-C 15bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy,

[0033] In addition, when L3 is a substituted aryl and the substituent of the aryl is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl may be selected from the group consisting of substituted or unsubstituted C5-C6 alkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. 20 Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl, substituted or unsubstituted C5-C 10aryl, etc.) (optionally, aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; aryl is optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof). Furthermore, when L3 is a substituted aryl and the substituent of the aryl is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is selected from the group consisting of a substituted or unsubstituted 5- to 25-membered heteroaryl (e.g., a substituted or unsubstituted 5- to 20-membered heteroaryl, a substituted or unsubstituted 5- to 15-membered heteroaryl, or a substituted or unsubstituted 5- to 10-membered heteroaryl);Optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinyl, selected from the group consisting of dinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1). For example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Furthermore, when L3 is a substituted aryl and the aryl substituent is a substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is selected from the group consisting of substituted or unsubstituted 4- to 20-membered heterocyclyl (e.g., substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted 4- to 10-membered heterocyclyl, or substituted or unsubstituted 4- to 8-membered heterocyclyl, etc.); optionally, the heterocyclyl is selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxa azacyclohexyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, dioxacyclohexenyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., a 4- to 15-membered bridged heterocyclyl, a 5- to 15-membered bridged heterocyclyl, or a 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (e.g., a 4- to 15-membered spiroheterocyclyl, a 5- to 15-membered spiroheterocyclyl, or a 7- to 15-membered spiroheterocyclyl; For example, 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); the heterocyclyl is an optionally substituted heterocyclyl, and the number of substituents is preferably one or more (for example, 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C-C alkyl, C-C cycloalkyl, hydroxy, amino, mercapto, halogen (for example, fluorine, chlorine, bromine, iodine, etc.), cyano, oxo, C-C alkoxy, deuterated C-C alkoxy, C-C alkylamino, halogenated C-C alkyl, halogenated C-C cycloalkyl, amino-substituted C-C alkylene, C-C alkyl-NHC(O)—, C-C alkyl-C(O)NH—, and any combination thereof.

[0157] In embodiment 106), the compounds of formulae I-1 and I-2 according to embodiment 104) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein L3 is selected from the group consisting of substituted or unsubstituted 5- to 25-membered heteroaryl (preferably substituted or unsubstituted 5- to 20-membered heteroaryl or substituted or unsubstituted 5- to 15-membered heteroaryl); more preferably, L3 is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl , pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, xanthe nyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, iridyl and n-butyl-1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124,Substituted heteroaryl refers to heteroaryl substituted one or more times (e.g., 1-4, 1-3, or 1-2 times) with a substituent, wherein the substituent is optionally selected from the group consisting of C-C alkyl, C-C cycloalkyl, hydroxy, amino, mercapto, halogen, deuterium, nitro, carbonyl, an ester group, an imido group, a phosphine oxide group, trifluoromethoxy, C-C alkoxy, C-C alkylamino, halogenated C-C alkyl, amino-substituted C-C alkylene, C-C alkyl-NHC(O)—, C-C alkyl-C(O)NH—, cyano, alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, aralkyl, arylalkenyl, alkylaryl, aralkylamino, heteroarylamino, arylamino, arylphosphino group, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, acenaphthenyl, or any combination thereof. Preferably, the substituents are optionally selected from the group consisting of C1-C3 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen, C1-C3 alkoxy, C1-C3 alkylamino, halogenated C1-C3 alkyl, amino-substituted C1-C3 alkylene, C1-C3 alkyl-NHC(O)-, C1-C3 alkyl-C(O)NH-, cyano, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or any combination thereof. Furthermore, when L3 is substituted heteroaryl and the heteroaryl substituent is substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl may be substituted or unsubstituted C3-C6 cycloalkyl. 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C 10cycloalkyl, substituted or unsubstituted C3-C6 cycloalkyl, etc.; optionally, cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl, C5-C 15 Spirocycloalkyl, or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged Cycloalkyl, C5-C 15 Bridged cycloalkyl, or C7-C 15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy,

[0033] In addition, when L3 is a substituted heteroaryl and the substituent of the heteroaryl is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl may be selected from the group consisting of substituted or unsubstituted C5-C6 alkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. 20 Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl, substituted or unsubstituted C5-C 10aryl, etc.); optionally, the aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; the aryl is an optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1). For example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Furthermore, when L3 is a substituted heteroaryl and the substituent of the heteroaryl is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5- to 25-membered heteroaryl (preferably a substituted or unsubstituted 5- to 20-membered heteroaryl, a substituted or unsubstituted 5- to 15-membered heteroaryl, or a substituted or unsubstituted 5- to 10-membered heteroaryl) (optionally, the substituted or unsubstituted heteroaryl is pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetra ... tolazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl,phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl; the substituted or unsubstituted heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-22, 1-23, 1-24, 1-25, 1-26, 1-27, 1-28, 1-29, 1-30, 1-31, 1-32, 1-33, 1-34, 1-35, 1-36, 1-37, 1-38, 1-39, 1-40, 1-41, 1-42, 1-43, 1-44, 1-45, 1-46, 1-47, 1-48, 1-49, 1-50, 1-51, 1-52, 1-53, 1-54, 1-55, 1-56, 1-57, 1-58, 1-5 -2, or 1), for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Furthermore, when L3 is a substituted heteroaryl and the heteroaryl substituent is a substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is selected from the group consisting of substituted or unsubstituted 4- to 20-membered heterocyclyl (e.g., substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted 4- to 10-membered heterocyclyl, or substituted or unsubstituted 4- to 8-membered heterocyclyl, etc.); optionally, the heterocyclyl is selected from the group consisting of azetidinyl, azacyclopentyl, azacyclopentyl, Hexyl, azepanyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl, 5- to 15-membered bridged, Heterocyclyl, or 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, azabicycloheptanyl, azabicyclooctyl, or spiroheterocyclyl (e.g., 4- to 15-membered spiroheterocyclyl, 5- to 15-membered spiroheterocyclyl, or 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); heterocyclyl is an optionally substituted heterocyclyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0158] In embodiment 107) the compounds of formulae I-1 and I-2 according to embodiment 104) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein L3 is selected from the group consisting of substituted or unsubstituted 4- to 20-membered heterocyclyl (e.g., substituted or unsubstituted 4- to 15-membered heterocyclyl); preferably, L3 is selected from the group consisting of azetidinyl, azacyclopentyl, azacyclohexyl, azepanyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothien ... is selected from the group consisting of hydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., a 4- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, azabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (e.g., a 4- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl). The heterocyclyl may be unsubstituted or substituted (e.g., mono-, di-, tri-, or poly-substituted) as clearly defined, where the substituents are optionally deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, carbonyl, ester, imido, phosphine oxide, trifluoromethoxy, oxo, optionally deuterated 1-C alkyl, halogenated C-C alkyl, optionally deuterated 3-C cycloalkyl, optionally deuterated 1-C alkyl, optionally deuterated 2-C cycloalkyl, optionally deuterated 3-C cycloalkyl, optionally deuterated 4-C cycloalkyl, optionally deuterated 5-C cycloalkyl, optionally deuterated 6-C cycloalkyl, optionally deuterated 7-C cycloalkyl, optionally deuterated 8-C cycloalkyl, optionally deuterated 9-C cycloalkyl, optionally deuterated 10-C cycloalkyl, optionally deuterated 11-C cycloalkyl, optionally deuterated 12-C cycloalkyl, optionally deuterated 13-C cycloalkyl, optionally deuterated 14-C cycloalkyl, optionally deuterated 15-C cycloalkyl, optionally deuterated 16-C cycloalkyl, optionally deuterated 17-C cycloalkyl, optionally deuterated 18-C cycloalkyl, optionally deuterated 19 ... and any combination thereof.Preferably, the substituents are selected from the group consisting of deuterium, hydroxy, amino, mercapto, nitro, halogen, cyano, oxo, optionally deuterated 1-C6 alkyl, halogenated C1-C6 alkyl, optionally deuterated 3-C6 cycloalkyl, optionally deuterated 1-C6 alkoxy, C1-C4 alkyl-NH-, NH2-C1-6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, and any combination thereof. Furthermore, when L3 is substituted heterocyclyl and the heterocyclyl substituent is substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl may be substituted or unsubstituted C3-C6 alkyl. 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C 10 cycloalkyl, substituted or unsubstituted C3-C6 cycloalkyl, etc.; optionally, cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl, C5-C 15 Spirocycloalkyl, or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged Cycloalkyl, C5-C 15 Bridged cycloalkyl, or C7-C 15bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy,

[0033] In addition, when L3 is a substituted heterocyclyl and the substituent of the heterocyclyl is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl may be selected from the group consisting of substituted or unsubstituted C5-C6 alkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. 20 Aryl (e.g., substituted or unsubstituted C5-C 15 Aryl, substituted or unsubstituted C5-C 10aryl, etc.); optionally, the aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; the aryl is an optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1). For example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Furthermore, when L3 is a substituted heterocyclyl and the substituent of the heterocyclyl is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is selected from the group consisting of a substituted or unsubstituted 5- to 25-membered heteroaryl (preferably a substituted or unsubstituted 5- to 20-membered heteroaryl, a substituted or unsubstituted 5- to 15-membered heteroaryl, or a substituted or unsubstituted 5- to 10-membered heteroaryl);Optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinyl, selected from the group consisting of dinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1). For example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Furthermore, when L3 is a substituted heterocyclyl and the substituent of the heterocyclyl is a substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is a substituted or unsubstituted 4- to 20-membered heterocyclyl (e.g., a substituted or unsubstituted 4- to 15-membered heterocyclyl, a substituted or unsubstituted 4- to 10-membered heterocyclyl, or a substituted or unsubstituted 4- to 8-membered heterocyclyl, etc.) (optionally, the substituted or unsubstituted heterocyclyl is azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, etc.). azacyclohexyl, dioxacyclohexenyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl or 5- to 15-membered bridged heterocyclyl or 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (e.g., 4- to 15-membered spiroheterocyclyl or 5- to 15-membered spiroheterocyclyl or 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); the substituted or unsubstituted heterocyclyl is optionally substituted heterocyclyl; The number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), and for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0159] In embodiment 108) the compounds of formula I-1 and I-2 according to embodiment 104) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein L3 is a substituted or unsubstituted C3-C 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Preferably, L3 is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl, C5-C 15 Spirocycloalkyl, or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged Cycloalkyl, C5-C 15 Bridged cycloalkyl, or C7-C 15and bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl), wherein the "cycloalkyl" is optionally substituted, and the substituents are preferably trifluoromethyl, mercapto, hydroxy, amino, halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl, deuterium, nitro, carbonyl, ester group, imido group, phosphine oxide group, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, deuterated alkyl, amino-substituted alkylene, alkyl and one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents selected from the group consisting of aryl-NHC(O)-, alkyl-C(O)NH-, substituted or unsubstituted cycloalkyl, deuterated cycloalkyl, alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, acenaphthenyl, oxo group, or any combination thereof. Furthermore, the substituents are preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1) substituents selected from the group consisting of trifluoromethyl, mercapto, hydroxy, amino, halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or any combination thereof. Furthermore, when L3 is a substituted cycloalkyl and the cycloalkyl substituent is a substituted or unsubstituted cycloalkyl, the substituted or unsubstituted cycloalkyl is preferably a substituted or unsubstituted C3-C 20 Cycloalkyl (e.g., substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted C3-C 10cycloalkyl, substituted or unsubstituted C3-C6 cycloalkyl, etc. (optionally, the substituted or unsubstituted cycloalkyl may be cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C3-C 15 Spirocycloalkyl, C5-C 15 Spirocycloalkyl, or C7-C 15 spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C-C 15 Bridged Cycloalkyl, C5-C 15 Bridged cycloalkyl, or C7-C 15 bridged cycloalkyl, such as adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; the substituted or unsubstituted cycloalkyl is optionally substituted cycloalkyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are C1-C6 alkyl, C1-C6 alkoxy, , C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Furthermore, when L3 is a substituted cycloalkyl, and the substituent of the cycloalkyl is a substituted or unsubstituted aryl, the substituted or unsubstituted aryl may be selected from the group consisting of a substituted or unsubstituted C5-C6 alkyl, a hydroxyl group, an amino group, a mercapto group, a halogen group (e.g., fluorine, chlorine, bromine, iodine, etc.), a cyano group, an oxo group, a deuterated C1-C6 alkoxy, a C1-C4 alkylamino, a halogenated C1-C6 alkyl, a halogenated C3-C6 cycloalkyl, an amino-substituted C1-C6 alkylene, a C1-C4 alkyl-NHC(O)-, a C1-C4 alkyl-C(O)NH-, and any combination thereof. 20 Aryl (e.g., substituted or unsubstituted C5-C 15Aryl, substituted or unsubstituted C5-C 10aryl, etc.); optionally, the aryl is selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, 9,9'-dimethylfluorenyl, etc.; the aryl is an optionally substituted aryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1). For example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Furthermore, when L3 is a substituted cycloalkyl and the substituent of the cycloalkyl is a substituted or unsubstituted heteroaryl, the substituted or unsubstituted heteroaryl is selected from the group consisting of a substituted or unsubstituted 5- to 25-membered heteroaryl (preferably a substituted or unsubstituted 5- to 20-membered heteroaryl, a substituted or unsubstituted 5- to 15-membered heteroaryl, or a substituted or unsubstituted 5- to 10-membered heteroaryl);Optionally, heteroaryl is selected from the group consisting of pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, dithiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, acridinyl, xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinyl, selected from the group consisting of dinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl, phenazinyl, imidazopyridinyl, phenanthridinyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl;The heteroaryl is an optionally substituted heteroaryl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1). For example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof. Furthermore, when L3 is a substituted cycloalkyl and the cycloalkyl substituent is a substituted or unsubstituted heterocyclyl, the substituted or unsubstituted heterocyclyl is selected from the group consisting of substituted or unsubstituted 4- to 20-membered heterocyclyl (e.g., substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted 4- to 10-membered heterocyclyl, or substituted or unsubstituted 4- to 8-membered heterocyclyl, etc.); optionally, the heterocyclyl is selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclyl, azacyclohexyl, dioxacyclohexenyl, azacycloheptanyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., 4- to 15-membered bridged heterocyclyl or 5- to 15-membered bridged heterocyclyl or 7- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, diazabicycloheptanyl, azabicyclooctyl), or spiroheterocyclyl (e.g., 4- to 15-membered spiroheterocyclyl or 5- to 15-membered spiroheterocyclyl or 7- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); heterocyclyl is an optionally substituted heterocyclyl, and the number of substituents is preferably one or more (e.g., 1-5, 1-4, 1-3, 1-2, or 1), for example, the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, hydroxy, amino, mercapto, halogen (e.g., fluorine, chlorine, bromine, iodine, etc.), cyano, oxo group, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C1-C4 alkylamino, halogenated C1-C6 alkyl, halogenated C3-C6 cycloalkyl, amino-substituted C1-C6 alkylene, C1-C4 alkyl-NHC(O)-, C1-C4 alkyl-C(O)NH-, and any combination thereof.

[0160] In embodiment 109), the compounds of formulae I-1 and I-2 according to embodiment 104) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein the substituted L3 substituents are optionally one or more substituents selected from the group consisting of deuterium, halogen, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, halogenated C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, linear or branched C1-C5 alkyl or halogenated C1-C5 alkyl.

[0161] In embodiment 110), with respect to compounds of formulae I-1 and I-2 according to any one of embodiments 104) to 109) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, L3 is [ka] selected from the group consisting of: wherein X6 is selected from the group consisting of deuterium, halogen, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, halogenated C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, halogenated C1-C6 alkyl, or straight or branched C1-C6 alkyl; optionally, halogen can be, for example, F, Cl, Br, or I. Optionally, C1-C6 alkoxy can include, but is not limited to, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentoxy, isopentyloxy, n-hexyloxy, 3,3-dimethylbutoxy, 2-ethylbutoxy, etc. Optionally, halogenated C1-C6 alkoxy can be, for example, trifluoromethoxy, etc. Optionally substituted or unsubstituted amino may include amino, N-methylamino, N-ethylamino, N-phenylamino, N,N-dimethylamino, N,N-diethylamino, etc. Optionally substituted or unsubstituted silyl may be, for example, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, vinyldimethylsilyl, propyldimethylsilyl, triphenylsilyl, diphenylsilyl, phenylsilyl, etc. Optionally substituted or unsubstituted boryl may include, for example, trimethylboryl, triethylboryl, tert-butyldimethylboryl, triphenylboryl, phenylboryl, etc. Optionally, the straight or branched C1-C6 alkyl includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methyl-butyl, 1-ethyl-butyl, pentyl, n-pentyl, isopentyl, neopentyl, and tert-pentyl, and the straight or branched C1-C6 alkyl is optionally substituted, wherein the substituent is optionally one or more substituents selected from the group consisting of D (i.e., deuterium), halogen, hydroxy, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl (e.g., a 4- to 8-membered heterocycle), or any combination thereof; m is an integer of 0, 1, 2, 3, 4, or 5, and when m is an integer of 2, 3, 4, or 5, each X6 is the same or different; X7 and X9 are each independently selected from CH or N; each X8 is independently selected from the group consisting of O, S, or NH; R 17is selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, halogenated C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, halogenated C1-C5 alkyl, or straight or branched C1-C5 alkyl, where optionally, halogen can be, for example, F, Cl, Br, or I. Optionally, C1-C6 alkoxy can include, but is not limited to, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentoxy, isopentyloxy, n-hexyloxy, 3,3-dimethylbutoxy, 2-ethylbutoxy, etc. Optionally, halogenated C1-C6 alkoxy can be, for example, trifluoromethoxy, etc. Optionally substituted or unsubstituted amino may include amino, N-methylamino, N-ethylamino, N-phenylamino, N,N-dimethylamino, N,N-diethylamino, etc. Optionally substituted or unsubstituted silyl may be, for example, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, vinyldimethylsilyl, propyldimethylsilyl, triphenylsilyl, diphenylsilyl, phenylsilyl, etc. Optionally substituted or unsubstituted boryl may include, for example, trimethylboryl, triethylboryl, tert-butyldimethylboryl, triphenylboryl, phenylboryl, etc. Optionally, straight or branched chain C1-C5 alkyl includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methyl-butyl, 1-ethyl-butyl, pentyl, n-pentyl, isopentyl, neopentyl, and tert-pentyl, and said straight or branched chain C1-C5 alkyl is optionally substituted, where the substituent is optionally one or more substituents selected from the group consisting of D (i.e., deuterium), halogen, hydroxy, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl (e.g., a 4- to 8-membered heterocycle), or any combination thereof.

[0162] In embodiment 111), with respect to compounds of formula I-1 and I-2 according to any one of embodiments 97) to 110), or salts, enantiomers, stereoisomers, polymorphs, or solvates thereof, R a2 Further options for R are the same as those described in Formula I. a2 and L3 are the same or different; and R a2 must exist.

[0163] Particularly preferred are the compounds in Table 1 of the present invention and salts (especially pharmaceutically acceptable salts such as their hydrochloride salts), enantiomers, stereoisomers, polymorphs or solvates thereof. Table 1. Compounds of the present disclosure [Table 1] TIFF2026502207000021.tif155102TIFF2026502207000022.tif155102TIFF2026502207000023.tif155103TIFF2026502207000024.tif155102TIFF2026502207000025.tif155103TIFF2026502207000026.tif155102TIFF2026502207000027.tif156102TIFF2026502207000028.tif155103TIFF2026502207000029.tif155102TIFF2026502207000030.tif149103TIFF2026502207000031.tif155102TIFF2026502207000032.tif155103TIFF2026502207000033.tif156102TIFF2026502207000034.tif148102TIFF2026502207000035.tif155102TIFF2026502207000036.tif150103TIFF2026502207000037.tif155102TIFF2026502207000038.tif152102TIFF2026502207000039.tif155102TIFF2026502207000040.tif155102TIFF2026502207000041.tif155102TIFF2026502207000042.tif156102TIFF2026502207000043.tif155102TIFF2026502207000044.tif154102TIFF2026502207000045.tif150102TIFF2026502207000046.tif150103TIFF2026502207000047.tif149102TIFF2026502207000048.tif155102TIFF2026502207000049.tif155102TIFF2026502207000050.tif147102TIFF2026502207000051.tif153103TIFF2026502207000052.tif153103TIFF2026502207000053.tif150103TIFF2026502207000054.tif152102TIFF2026502207000055.tif156102TIFF202650 2207000056.tif156102TIFF2026502207000057.tif155102TIFF2026502207000058.tif89102.

[0164] Specifically, the above structures may be further substituted with one or more substituents selected from the group consisting of deuterium, halogen, nitrile, nitro, hydroxy, carbonyl, ester, imide, phosphine oxide, alkoxy, aryloxy, alkylthio, arylthio, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylheteroarylamino, arylphosphino, and heteroaryl.

[0165] In another aspect, the disclosure provides Embodiment A1): a compound of Formula A or a salt (including a pharmaceutically acceptable salt), enantiomer, stereoisomer, polymorph, or solvate thereof, wherein the chemical structure of said compound is represented as follows: [ka] Formula A In Formula A, X is selected from CO or CH2; L1 is selected from S or O; X1 is selected from the group consisting of substituted or unsubstituted straight or branched chain alkylene, or X1 is absent; X a is a structure of formula A1: [ka] Formula A1 wherein ring C is selected from the group consisting of substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, substituted or unsubstituted heterocyclylene, or substituted or unsubstituted cycloalkylene, and w represents an integer of 0 or 1; and Ring D represents a substituted or unsubstituted nitrogen-containing heterocyclyl; R a is selected from the group consisting of deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, halogenated alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R b1 , R b2 , R b3 , R b4 and R b5 are each independently selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, halogenated alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted straight or branched chain alkyl; and n represents an integer of 0, 1, 2, or 3, and when n represents an integer of 2 or 3, each R a are the same or different.

[0166] The compounds of Formula A provided in the present disclosure, or salts (including pharmaceutically acceptable salts), stereoisomers (including enantiomers), polymorphs, or solvates thereof, have CRBN E3 ubiquitin ligase binding activity and contribute to the recruitment of substrate proteins, and therefore may have immunomodulatory activity, anti-inflammatory activity, and antitumor activity, or may have excellent pharmacokinetic properties. The compounds of Formula A provided in the present disclosure, or salts, stereoisomers (including enantiomers), polymorphs, or solvates thereof, may be used as intermediates in the production of the compounds of Formula I of the present disclosure, or salts, stereoisomers (including enantiomers), polymorphs, or solvates thereof.

[0167] Embodiment A2): Compounds of formula A according to embodiment A1) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein X in formula A is CO.

[0168] Embodiment A3): Compounds of formula A according to embodiment A1) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein X in formula A is CH2.

[0169] Embodiment A4): Compounds of formula A according to embodiment A1) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein L1 in formula A is S.

[0170] Embodiment A5): Compounds of formula A according to embodiment A1) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein L1 in formula A is O.

[0171] In embodiment A6), the compound of formula A according to any one of embodiments A1) to A5) or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein X1 is a substituted or unsubstituted linear or branched alkylene. When X1 is a substituted or unsubstituted linear or branched alkylene, said X1 may be a substituted or unsubstituted linear or branched C1-C5 alkylene, or a substituted or unsubstituted linear or branched C1-C3 alkylene, etc.

[0172] In embodiment A7), the present invention relates to a compound of formula A according to any one of embodiments A1) to A6), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein when X1 is a substituted or unsubstituted linear or branched C1-C5 alkylene, the linear or branched C1-C5 alkylene may be methylene, ethylene, propylene, n-propylene, isopropylene, butylene, n-butylene, isobutylene, tert-butylene, sec-butylene, 1-methyl-butylene, 1-ethyl-butylene, pentylene, n-pentylene, isopentylene, neopentylene, tert-pentylene, or the like.

[0173] In embodiment A8), with respect to a compound of formula A according to any one of embodiments A1) to A7), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein when X1 is a substituted or unsubstituted linear or branched C1-C3 alkylene, the linear or branched alkylene can be, for example, methylene, ethylene, propylene, or isopropylene.

[0174] In embodiment A9), the compound of formula A according to any one of embodiments A1) to A8) or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein said X1 is selected from methylene.

[0175] In embodiment A10), the compound of formula A according to any one of embodiments A1) to A8) or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof is substituted with X1, wherein the substituted X1 substituents are optionally selected from the group consisting of deuterium, halogen, cyano, nitro, hydroxy, mercapto, carbonyl, ester, imido, amino, phosphine oxide, alkoxy, halogenated alkoxy, aryloxy, alkylthio, arylthio, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino, and heteroaryl, acenaphthenyl, and the like, or any combination thereof. The optionally substituted substituents of X1 may be, for example, one or more substituents selected from the group consisting of D (i.e., deuterium), halogen, hydroxy, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl (e.g., a 4- to 8-membered heterocycle), nitro, mercapto, carbonyl, ester group, imido group, amino, phosphine oxide group, alkoxy, deuterated alkoxy, trifluoromethoxy, aryloxy, alkylthio group, arylthio group, alkylsulfonyl, arylsulfonyl, silyl, boryl, alkyl, deuterated alkyl, alkyl halide, amino-substituted alkylene, alkyl-NHC(O)-, alkyl-C(O)NH-, cycloalkyl, deuterated cycloalkyl, alkenyl, aryl, aralkyl, arylalkenyl, alkylaryl, alkylamino, aralkylamino, heteroarylamino, arylamino, arylphosphino group, heteroaryl, acenaphthenyl, oxo group, or any combination thereof. Further optionally, the substituents of the substituted X1 may be selected from the group consisting of, for example, deuterium, halogen, nitro, mercapto, hydroxy, cyano, C1-C3 alkyl, C1-C3 alkoxy, halogenated C1-C3 alkoxy, halogenated C1-C3 alkyl, amino, silyl, boryl, or any combination thereof.Further optionally, the "substituted" substituents may be selected from the group consisting of, for example, deuterium, F, Cl, methoxy, methyl, hydroxy, or any combination.

[0176] In embodiment A11), with respect to a compound of formula A according to any one of embodiments A1) to A5), or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, wherein X1 is absent.

[0177] In embodiment A12), a compound of formula A according to any one of embodiments A1) to A11) or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein X a is a structure of formula A1: [ka] Formula A1 represents wherein ring C is a substituted or unsubstituted C5-C 30 arylene, substituted or unsubstituted 5- to 30-membered heteroarylene, substituted or unsubstituted 4- to 30-membered heterocyclylene, or substituted or unsubstituted C3-C 30 cycloalkylene; preferably, ring C is selected from the group consisting of substituted or unsubstituted C-C 20 arylene, substituted or unsubstituted 5- to 20-membered heteroarylene, substituted or unsubstituted 4- to 20-membered heterocyclylene, or substituted or unsubstituted C3-C 20 cycloalkylene; w represents an integer of 0 or 1; and Ring D represents a substituted or unsubstituted 4- to 30-membered nitrogen-containing heterocyclyl; preferably, ring D represents a substituted or unsubstituted 4- to 20-membered nitrogen-containing heterocyclyl.

[0178] In embodiment A13), with respect to a compound of formula A according to any one of embodiments A1) to A12) or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, X a is a structure of formula A1: [ka] Formula A1 represents wherein ring C is a substituted or unsubstituted C5-C 15 arylene, substituted or unsubstituted 5- to 15-membered heteroarylene, substituted or unsubstituted 4- to 15-membered heterocyclylene, or substituted or unsubstituted C3-C 15 cycloalkylene, wherein the substituents of said substituted Ring C are optionally one or more substituents selected from the group consisting of halogen, mercapto, hydroxy, amino, cyano, C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkyl, or any combination thereof; w represents an integer of 0 or 1; and Ring D represents a substituted or unsubstituted 4- to 15-membered nitrogen-containing heterocyclyl.

[0179] In embodiment A14), with respect to compounds of formula A according to any one of embodiments A1) to A13) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, ring C is selected from the group: Azetidinylene, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, dihydropyranylene, tetrahydrothienylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, dioxacyclohexylene, dioxacyclohexenylene, azacyclohepta annylene, azacyclooctylene, diazacycloheptanylene, diazacyclooctylene, bridged heterocyclylene (e.g., a 5- to 15-membered bridged heterocyclylene, such as azabicyclohexylene, azabicycloheptanylene, or azabicyclooctylene), or spiroheterocyclylene (e.g., a 5- to 15-membered spiroheterocyclylene, such as 3-azaspiro[5.5]undecanylene or 7-azaspiro[3.5]nonanylene); or Furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzo isoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2 a]pyridylene, 1H-pyrrolo[3,2-b]pyridylene, 1H-pyrrolo[2,3-b]pyridylene, pyrrolo[2,1-b]thiazolylene and imidazo[2,1-b]thiazolylene; or Cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decalinylene, octahydrocyclopentalenylene, octahydro-1H-indenylene, spirocycloalkylene (e.g., C5-C 15 spirocycloalkylene, such as spiro[3.3]heptylene, spiro[2.5]octylene, spiro[3.5]nonylene, spiro[4.4]nonylene, spiro[4.5]decylene, or spiro[5.5]undecylene), or bridged cycloalkylene (e.g., C-C 15 a bridged cycloalkylene, such as adamantanylene, noradamantanylene, bornylene, biscyclo[2.2.1]heptylene, 2-oxobiscyclo[2.2.1]heptylene or biscyclo[2.2.1]heptenylene); or selected from the group consisting of phenylene or naphthylene; wherein said ring C is further optionally substituted with one or more substituents selected from the group consisting of deuterium, halogen, nitro, mercapto, hydroxy, cyano, C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, halogenated C1-C6 alkyl, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, or any combination thereof.

[0180] In embodiment A15), with respect to compounds of formula A according to any one of embodiments A1) to A14) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, ring D is selected from the group: selected from the group consisting of azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, azacycloheptanyl, azacyclooctyl, diazacycloheptanyl, diazacyclooctyl, nitrogen-containing bridged heterocyclyl (e.g., a 5- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, or azabicyclooctyl), or nitrogen-containing spiroheterocyclyl (e.g., a 5- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); wherein said ring D is further optionally substituted with one or more substituents selected from the group consisting of deuterium, halogen, nitro, mercapto, hydroxy, cyano, oxo, C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, halogenated C1-C6 alkyl, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, or any combination thereof.

[0181] In embodiment A16), with respect to a compound of formula A according to any one of embodiments A1) to A15) or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, X a teeth, [ka] selected from the group consisting of: where R d1 , R d2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, halogenated C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched C1-C5 alkyl; and R d1 , R d2 is not hydrogen at the same time.

[0182] In embodiment A17), compounds of formula A according to embodiment A16) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R d1 , R d2 are each independently selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, halogenated C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched C1-C5 alkyl; and R d1 , R d2is not simultaneously hydrogen. In a specific embodiment, optionally, halogen may be, for example, F, Cl, Br, or I. Optionally, C1-C6 alkoxy may include, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentoxy, isopentyloxy, n-hexyloxy, 3,3-dimethylbutoxy, and 2-ethylbutoxy, etc., but are not limited thereto. Optionally, halogenated C1-C6 alkoxy may be, for example, trifluoromethoxy, etc. Optionally, substituted or unsubstituted amino includes amino, N-methylamino, N-ethylamino, N-phenylamino, N,N-dimethylamino, N,N-diethylamino, etc. Optionally, substituted or unsubstituted silyl can be, for example, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, vinyldimethylsilyl, propyldimethylsilyl, triphenylsilyl, diphenylsilyl, phenylsilyl, etc. Optionally, substituted or unsubstituted boryl can include, for example, trimethylboryl, triethylboryl, tert-butyldimethylboryl, triphenylboryl, phenylboryl, etc. Optionally, straight or branched chain C1-C5 alkyl can include, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methyl-butyl, 1-ethyl-butyl, pentyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, etc. wherein the linear or branched C1-C5 alkyl is optionally substituted, and the substituent is optionally one or more substituents selected from the group consisting of D (i.e., deuterium), halogen, hydroxy, cyano, C1-C3 alkyl, C1-C3 alkoxy, trifluoromethyl, heterocyclyl (e.g., a 4- to 8-membered heterocycle), or any combination thereof.

[0183] In embodiment A18), a compound of formula A according to any one of embodiments A1 to A17) or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein R ais selected from the group consisting of deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, halogenated alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted straight or branched chain alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0184] In embodiment A19), compounds of formula A according to embodiment A18) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a is deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, halogenated C1-C6 alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched C1-C5 alkyl, substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted C5-C 15 It is selected from the group consisting of aryl, or substituted or unsubstituted 5- to 15-membered heteroaryl.

[0185] In embodiment A20), compounds of formula A according to embodiment A18) or A19) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, wherein R a is deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, C1-C6 alkoxy, trifluoromethoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched C1-C5 alkyl, substituted or unsubstituted C3-C 15 Cycloalkyl, substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted C5-C 15 It is selected from the group consisting of aryl, or substituted or unsubstituted 5- to 15-membered heteroaryl.

[0186] In embodiment A21), for compounds of formula A according to embodiment A20) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is deuterium.

[0187] In embodiment A22), for compounds of formula A according to embodiment A20) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a halogen, optionally wherein the halogen is F, Cl, Br, or I.

[0188] In embodiment A23), for compounds of formula A according to embodiment A20) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is nitro.

[0189] In embodiment A24), for compounds of formula A according to embodiment A20) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is cyano.

[0190] In embodiment A25), for compounds of formula A according to embodiment A20) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is an amino.

[0191] In embodiment A26), for compounds of formula A according to embodiment A20) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is hydroxy.

[0192] In embodiment A27), for compounds of formula A according to embodiment A20) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is mercapto.

[0193] In embodiment A28), for compounds of formula A according to embodiment A20) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is alkoxy. ais an alkoxy, the alkoxy is a C1-C6 alkoxy. The C1-C6 alkoxy may include, but is not limited to, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentoxy, isopentyloxy, n-hexyloxy, 3,3-dimethylbutoxy, 2-ethylbutoxy, etc.

[0194] In embodiment A29), for compounds of formula A according to embodiment A20) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a halogenated alkoxy. a is a halogenated alkoxy, said halogenated alkoxy is a halogenated C1-C6 alkoxy; further optionally, said halogenated C1-C6 alkoxy is trifluoromethoxy, etc.

[0195] In embodiment A30), for compounds of formula A according to embodiment A20) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a substituted or unsubstituted amino. Optionally substituted or unsubstituted amino includes amino, N-methylamino, N-ethylamino, N-phenylamino, N,N-dimethylamino, N,N-diethylamino, and the like.

[0196] In embodiment A31), for compounds of formula A according to embodiment A20) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a substituted or unsubstituted silyl. Optionally, the substituted or unsubstituted silyl is specifically trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, vinyldimethylsilyl, propyldimethylsilyl, triphenylsilyl, diphenylsilyl, phenylsilyl, and the like.

[0197] In embodiment A32), for compounds of formula A according to embodiment A20) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, Ra is a substituted or unsubstituted boryl. Optionally, the substituted or unsubstituted boryl is specifically trimethylboryl, triethylboryl, tert-butyldimethylboryl, triphenylboryl, phenylboryl, and the like.

[0198] In embodiment A33), for compounds of formula A according to embodiment A20) or salts, enantiomers, stereoisomers, polymorphs or solvates thereof, R a is a substituted or unsubstituted straight or branched chain alkyl. Optionally, the number of carbon atoms may be, for example, C-C 30 , C1-C 25 , C1-C 20 , C1-C 15 , C1-C 10 , C1-C5, C1-C3, etc. Preferably, it is a straight or branched C1-C 10 and optionally straight or branched C-C alkyl. 10 Alkyl includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methylbutyl, 1-ethylbutyl, pentyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 4-methyl-2-pentyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl, n-heptyl, 1-methylhexyl,...

Claims

1. A compound of the chemical structure represented by formula I, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, 【Chemistry 1】 Formula I In Formula I, X is CO or CH ２ Selected from: L １ is selected from S or O; X １ is selected from the group consisting of substituted or unsubstituted straight or branched chain alkylene, or X １ does not exist; X ２ represents a structure of formula II, 【Chemistry 2】 Formula II In Formula II, ring A and ring B are each independently selected from the group consisting of substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, substituted or unsubstituted heterocyclylene, or substituted or unsubstituted cycloalkylene; t represents an integer of 0, 1, or 2; and The symbol # is X ３ represents the connection point with; X ３ is CR １ , N, or CO, where R １ is selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, trifluoromethoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched alkyl, or substituted or unsubstituted cycloalkyl; R ａ１ is selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocyclyl; R ａ２ is selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocyclyl, or R ａ２ does not exist; and X ３ When represents CO, R ａ２ does not exist and R ａ１ is not hydrogen or deuterium, and R ａ２ When represents hydrogen or deuterium, X ３ is CR １ or N, and R ａ１ is not hydrogen or deuterium; R ａ is selected from the group consisting of deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, halogenated alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R ｂ１ , R ｂ２ , R ｂ３ , R ｂ４ and R ｂ５ are each independently selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, halogenated alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted straight or branched chain alkyl; and n represents an integer of 0, 1, 2, or 3, and when n represents an integer of 2 or 3, each R ａ are the same or different compounds or salts, enantiomers, stereoisomers, polymorphs or solvates thereof.

2. X １ is a substituted or unsubstituted straight or branched chain C １ -C ５ represents alkylene, or X １ does not exist; and / or X ２ represents a structure of formula II, 【Transformation 3】 Formula II In formula II, ring A is a substituted or unsubstituted C ５ -C ３０ arylene, substituted or unsubstituted 5- to 30-membered heteroarylene, substituted or unsubstituted 4- to 30-membered heterocyclylene, or substituted or unsubstituted C ３ -C ３０ cycloalkylene; preferably, ring A is selected from the group consisting of substituted or unsubstituted C ５ -C ２０ arylene, substituted or unsubstituted 5- to 20-membered heteroarylene, substituted or unsubstituted 4- to 20-membered heterocyclylene, or substituted or unsubstituted C ３ -C ２０ cycloalkylene; Ring B is a substituted or unsubstituted C ５ -C ３０ arylene, substituted or unsubstituted 5- to 30-membered heteroarylene, substituted or unsubstituted 4- to 30-membered heterocyclylene, or substituted or unsubstituted C ３ -C ３０ cycloalkylene; preferably, ring B is selected from the group consisting of substituted or unsubstituted C ５ -C ２０ arylene, substituted or unsubstituted 5- to 20-membered heteroarylene, substituted or unsubstituted 4- to 20-membered heterocyclylene, or substituted or unsubstituted C ３ -C ２０ cycloalkylene; t represents an integer of 0, 1, or 2; preferably, t represents an integer of 0 or 1; and The symbol # is X ３ represents the connection point with; and / or R １ is hydrogen, deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, trifluoromethoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched C １ -C １０ Alkyl, or substituted or unsubstituted C ３ -C １５ cycloalkyl; and / or R ａ１ is hydrogen, deuterium, substituted or unsubstituted C ５ -C ３０ Aryl, substituted or unsubstituted 5- to 30-membered heteroaryl, substituted or unsubstituted C ３ -C ３０ cycloalkyl, or substituted or unsubstituted 4- to 30-membered heterocyclyl; preferably, R ａ１ is hydrogen, deuterium, substituted or unsubstituted C ５ -C ２０ Aryl, substituted or unsubstituted 5- to 20-membered heteroaryl, substituted or unsubstituted C ３ -C ２０ selected from the group consisting of cycloalkyl, or substituted or unsubstituted 4- to 20-membered heterocyclyl; and / or R ａ２ is hydrogen, deuterium, substituted or unsubstituted C ５ -C ３０ Aryl, substituted or unsubstituted 5- to 30-membered heteroaryl, substituted or unsubstituted C ３ -C ３０ cycloalkyl, or substituted or unsubstituted 4- to 30-membered heterocyclyl, or R ａ２ is absent; preferably, R ａ２ is hydrogen, deuterium, substituted or unsubstituted C ５ -C ２０ Aryl, substituted or unsubstituted 5- to 20-membered heteroaryl, substituted or unsubstituted C ３ -C ２０ cycloalkyl, or substituted or unsubstituted 4- to 20-membered heterocyclyl, or R ａ２ does not exist; and / or R ａ is deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, C １ -C ６ Alkoxy, halogenated C １ -C ６ Alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted straight or branched chain C １ -C ５ Alkyl, substituted or unsubstituted C ３ -C １５ Cycloalkyl, substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted C ５ -C １５ aryl, or substituted or unsubstituted 5- to 15-membered heteroaryl; preferably, R ａ is deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, C １ -C ６ Alkoxy, trifluoromethoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted straight or branched chain C １ -C ５ Alkyl, substituted or unsubstituted C ３ -C １５ Cycloalkyl, substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted C ５ -C １５ aryl, or substituted or unsubstituted 5-15 membered heteroaryl; and / or R ｂ１ , R ｂ２ , R ｂ３ , R ｂ４ and R ｂ５ are each independently hydrogen, deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, C １ -C ６ Alkoxy, halogenated C １ -C ６ Alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, or substituted or unsubstituted straight or branched chain C １ -C ５ alkyl; preferably, R ｂ１ , R ｂ２ , R ｂ３ , R ｂ４ and R ｂ５ are each independently hydrogen, deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, C １ -C ６ Alkoxy, trifluoromethoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, or substituted or unsubstituted straight or branched chain C １ -C ５ 2. The compound of claim 1, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, characterized in that:

3. The chemical structure of the compound is as shown in Formula I-1 or Formula I-2, 【Chemistry 4】 Formula I-1 【Transformation 5】 Formula I-2 In formula I-1 or formula I-2, X, L １ , X １ ~X ２ , R ａ , R ｂ１ , R ｂ２ , R ｂ３ , R ｂ４ and R ｂ５ , n is as defined in claim 1 or claim 2; L ２ is a substituted or unsubstituted C ５ -C ３０ Arylene, substituted or unsubstituted 5- to 30-membered heteroarylene, substituted or unsubstituted C ３ -C ３０ cycloalkylene, or substituted or unsubstituted 4- to 30-membered heterocyclylene, or L ２ Not present; L ３ is a substituted or unsubstituted C ５ -C ３０ Aryl, substituted or unsubstituted 5- to 30-membered heteroaryl, substituted or unsubstituted C ３ -C ３０ cycloalkyl, or substituted or unsubstituted 4- to 30-membered heterocyclyl; R ａ２ is a substituted or unsubstituted C ５ -C ３０ Aryl, substituted or unsubstituted 5- to 30-membered heteroaryl, substituted or unsubstituted C ３ -C ３０ cycloalkyl, or substituted or unsubstituted 4- to 30-membered heterocyclyl; Here, in formula I-1, X ３ is CR １ or N, and in formula I-2, X ３ is CR １ , N, or CO, where R １ 3. A compound according to claim 1 or 2, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, characterized in that:

4. X １ is selected from the group consisting of methylene, ethylene, propylene or isopropylene, or X １ The compound according to any one of claims 1 to 3, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein:

5. X ２ represents a structure of formula II, 【Transformation 6】 Formula II In formula II, ring A is a substituted or unsubstituted C ５ -C １５ arylene, substituted or unsubstituted 5- to 15-membered heteroarylene, substituted or unsubstituted 4- to 15-membered heterocyclylene, or substituted or unsubstituted C ３ -C １５ cycloalkylene, wherein the substituents of said substituted ring A are optionally selected from the group consisting of halogen, mercapto, hydroxy, amino, cyano, C １ -C ６ Alkyl, C １ -C ６ Alkoxy, halogenated C １ -C ６ one or more substituents selected from the group consisting of alkyl, aryl, arylsulfonyl ... Ring B is a substituted or unsubstituted C ５ -C １５ arylene, substituted or unsubstituted 5- to 15-membered heteroarylene, substituted or unsubstituted 4- to 15-membered heterocyclylene, or substituted or unsubstituted C ３ -C １５ wherein the substituents of said substituted Ring B are optionally selected from the group consisting of halogen, mercapto, hydroxy, amino, cyano, C １ -C ６ Alkyl, C １ -C ６ Alkoxy, halogenated C １ -C ６ one or more substituents selected from the group consisting of alkyl, aryl, arylsulfonyl ... t represents an integer of 0, 1, or 2; preferably, t represents an integer of 0 or 1; and The symbol # is X ３ The compound according to any one of claims 1 to 3, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, characterized in that it represents a connection point with

6. Ring A and ring B each independently represent one of the following groups: Azetidinylene, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, dihydropyranylene, tetrahydrothienylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, dioxacyclohexylene, dioxacyclohexenylene, azacyclohepta annylene, azacyclooctylene, diazacycloheptanylene, diazacyclooctylene, bridged heterocyclylene (e.g., a 5- to 15-membered bridged heterocyclylene, such as azabicyclohexylene, azabicycloheptanylene, or azabicyclooctylene), or spiroheterocyclylene (e.g., a 5- to 15-membered spiroheterocyclylene, such as 3-azaspiro[5.5]undecanylene or 7-azaspiro[3.5]nonanylene); or Furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzo isoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2a]pyridylene, 1H-pyrrolo[3,2-b]pyridylene, 1H-pyrrolo[2,3-b]pyridylene, pyrrolo[2,1-b]thiazolylene and imidazo[2,1-b]thiazolylene; or Cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decalinylene, octahydrocyclopentalenylene, octahydro-1H-indenylene, spirocycloalkylene (e.g., C ５ -C １５ spirocycloalkylene, for example spiro[3.3]heptylene, spiro[2.5]octylene, spiro[3.5]nonylene, spiro[4.4]nonylene, spiro[4.5]decylene, or spiro[5.5]undecylene), or bridged cycloalkylene (for example, C ５ -C １５ a bridged cycloalkylene, such as adamantanylene, noradamantanylene, bornylene, biscyclo[2.2.1]heptylene, 2-oxobiscyclo[2.2.1]heptylene, or biscyclo[2.2.1]heptenylene; or selected from the group consisting of phenylene or naphthylene; wherein the ring A and the ring B each independently optionally further include deuterium, halogen, nitro, mercapto, hydroxy, cyano, C １ -C ６ Alkyl, C １ -C ６ Alkoxy, halogenated C １ -C ６ Alkoxy, halogenated C １ -C ６ The compound according to any one of claims 1 to 3, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, characterized in that it is substituted with one or more substituents selected from the group consisting of alkyl, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, or any combination thereof.

7. X ２ teeth, 【Transformation 7】 selected from the group consisting of: Here, R ｄ１ , R ｄ２ are each independently hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, C １ -C ６ Alkoxy, halogenated C １ -C ６ Alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted straight or branched chain C １ -C ５ alkyl; and R ｄ１ , R ｄ２ 6. The compound according to claim 3 or 5, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein is not simultaneously hydrogen.

8. R ａ２ If there exists X ３ is selected from CH or N; R ａ２ If does not exist, X ３ 2. The compound of claim 1, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein represents CO.

9. L ２ is selected from the group consisting of substituted or unsubstituted 5- to 20-membered heteroarylene (e.g., substituted or unsubstituted 5- to 15-membered heteroarylene); preferably, the heteroarylene is selected from the group consisting of pyridylene, pyrrolylene, pyrimidinylene, pyridazinylene, furanylene, thienylene, imidazolylene, pyrazolylene, oxazolylene, isoxazolylene, thiazolylene, isothiazolylene, triazolylene, oxadiazolylene, thiadiazolylene, tetrazolium, Rylene, pyranylene, thiopyranylene, pyrazinylene, pyridazinylene, thiazinylene, triazinylene, tetrazinylene, quinolinylene, isoquinolinylene, quinolinylene, quinazolinylene, quinoxalinylene, cinnolinylene, naphthyridinylene, acridinylene, xanthenylene, phenanthridinylene, diazanaphthylene, triazaindenylene, indolylene, indolinylene, indolizinylene, phthalazinylene, pyrazolopyridylene , pyrazolopyrimidinylene, pyridopyrimidinylene, pyridopyrazinylene, pyrazinopyrazinylene, benzothiazolylene, benzoxazolylene, benzimidazolylene, benzothienylene, benzofuranylene, isobenzofuranylene, dibenzothienylene, dibenzofuranylene, indazolylene, carbazolylene, benzocarbazolylene, dibenzocarbazolylene, indolocarbazolylene, indenocarbazolylene, phenazinylene, imidazolyl selected from the group consisting of imidazopyridinylene, phenazinylene, phenanthridinylene, phenanthrolinylene, phenothiazinylene, imidazopyridinylene, imidazophenanthridinylene, pyrrolopyridinylene, pyrrolothiazolylene, imidazothiazolylene, benzimidazoquinazolinylene, benzimidazophenanthridinylene, pyrenylene, dinaphthofuranylene, naphthobenzofuranylene, dinaphthothienylene, or naphthobenzothienylene; and / or L ２ is a substituted or unsubstituted C ３ -C ２０ Cycloalkylene (e.g., substituted or unsubstituted C ３ -C １５ cycloalkylene); preferably, L ２ is cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decalinylene, octahydrocyclopentalenylene, octahydro-1H-indenylene, spirocycloalkylene (e.g., C ５ -C １５ spirocycloalkylene, for example spiro[3.3]heptylene, spiro[2.5]octylene, spiro[3.5]nonylene, spiro[4.4]nonylene, spiro[4.5]decylene, or spiro[5.5]undecylene), or bridged cycloalkylene (for example, C ５ -C １５ bridged cycloalkylene, for example, adamantanylene, noradamantanylene, bornylene, biscyclo[2.2.1]heptylene, 2-oxobiscyclo[2.2.1]heptylene, or biscyclo[2.2.1]heptenylene; and / or L ２ is a substituted or unsubstituted C ５ -C ２０ Arylene (e.g., substituted or unsubstituted C ５ -C １５ arylene); preferably, L ２ is selected from the group consisting of phenylene, biphenylene, terphenylene, naphthylene, anthrylene, phenanthrylene, fluorenylene, 9,9′-dimethylfluorenylene; and / or L ２ is selected from the group consisting of substituted or unsubstituted 4- to 20-membered heterocyclylene (e.g., substituted or unsubstituted 4- to 15-membered heterocyclylene); preferably, L ２ is azetidinylene, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, dihydropyranylene, tetrahydrothienylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, dioxacyclohexylene, dioxacyclohexenylene, azacycloheptanylene, azacyclooctyl hexylene, diazacycloheptanylene, diazacyclooctylene, bridged heterocyclylene (e.g., 5- to 15-membered bridged heterocyclylene, such as azabicyclohexylene, azabicycloheptanylene, diazabicycloheptanylene, azabicyclooctylene), or spiroheterocyclylene (e.g., 5- to 15-membered spiroheterocyclylene, such as 3-azaspiro[5.5]undecanylene or 7-azaspiro[3.5]nonanylene); Here, the substituted L ２ The substituents may optionally be deuterium, halogen, nitro, mercapto, hydroxy, cyano, halogenated C １ -C ６ Alkyl straight or branched chain C １ -C ６ Alkyl, halogenated C １ -C ６ Alkoxy, C １ -C ６ Alkoxy, halogenated C １ -C ６ one or more substituents selected from the group consisting of alkyl, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, or any combination thereof; Or, L ２ 4. The compound of claim 3, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein:

10. L ２ teeth, 【Transformation 8】 selected from the group consisting of: Where: X ４ is selected from the group consisting of O, S, or NH; X ５ is O, S, or NR １６ where R １６ is hydrogen or C １ -C ３ represents alkyl; R ２ , R ３ , R ４ , R ５ , R ６ , R ７ , R ８ , R ９ , R １０ , R １１ , R １２ , R １３ , R １４ and R １５ are each independently hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, C １ -C ６ Alkoxy, halogenated C １ -C ６ Alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, linear or branched C １ -C ５ Alkyl or halogenated C １ -C ５ alkyl, wherein preferably said halogenated C １ -C ６ alkoxy is selected from trifluoromethoxy; or L ２ 10. The compound according to claim 3 or 9, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein:

11. L ３ , R ａ２ are each independently substituted or unsubstituted C ５ -C ２０ Aryl (e.g., substituted or unsubstituted C ５ -C １５ aryl); preferably, L ３ , R ａ２ are each independently selected from the group consisting of biphenyl, terphenyl, naphthyl, anthryl, phenanthryl, fluorenyl, and 9,9'-dimethylfluorenyl; and / or L ３ , R ａ２ are each independently selected from the group consisting of substituted or unsubstituted 5- to 25-membered heteroaryl (preferably substituted or unsubstituted 5- to 20-membered heteroaryl, or substituted or unsubstituted 5- to 15-membered heteroaryl); more preferably, L ３ , R ａ２ are each independently pyridyl, pyrrolyl, pyrimidinyl, pyridazinyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyrazinyl, oxazinyl, thiazinyl, triazinyl, tetrazinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, cinnolinyl, naphthyridinyl, acridinyl, xanthenyl, phenanthridinyl, diazanaphthyl, triazaindenyl, indolyl, indolinyl, indolizinyl, phthalazinyl, pyridopyrimidinyl, pyridopyraziny yl, pyrazinopyrazinyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzothienyl, benzofuranyl, dibenzothienyl, dibenzofuranyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl, phenazinyl, imidazopyridyl, phenanthrolinyl, phenothiazinyl, imidazopyridinyl, imidazophenanthridinyl, benzimidazoquinazolinyl, benzimidazophenanthridinyl, spiro[fluorene-9,9'-xanthene], pyrenyl, dinaphthofuranyl, naphthobenzofuranyl, dinaphthothienyl, or naphthobenzothienyl; and / or L ３ , R ａ２ are each independently selected from the group consisting of substituted or unsubstituted 4- to 20-membered heterocyclyl (e.g., substituted or unsubstituted 4- to 15-membered heterocyclyl); preferably, L ３ , R ａ２ are each independently selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, tetrahydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxacyclohexyl, dioxacyclohexenyl, azacycloheptanyl, azacyclooctyl, diazacycloheptanyl, diazacyclooctyl, bridged heterocyclyl (e.g., a 5- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, or azabicyclooctyl), or spiroheterocyclyl (e.g., a 5- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); and / or L ３ , R ａ２ are each independently substituted or unsubstituted C ３ -C ２０ Cycloalkyl (e.g., substituted or unsubstituted C ３ -C １５ cycloalkyl); preferably, L ３ , R ａ２ are each independently cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, decalinyl, octahydropentalenyl, octahydro-1H-indenyl, spirocycloalkyl (e.g., C ５ -C １５ spirocycloalkyl, such as spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, spiro[4.4]nonyl, spiro[4.5]decyl, or spiro[5.5]undecyl), or bridged cycloalkyl (e.g., C ５ -C １５ bridged cycloalkyl, for example, adamantanyl, noradamantanyl, bornyl, biscyclo[2.2.1]heptyl, 2-oxobiscyclo[2.2.1]heptyl, or bicyclo[2.2.1]heptenyl; Here, the substituted L ３ , R ａ２ The substituents are each independently optionally selected from deuterium, halogen, nitro, cyano, hydroxy, mercapto, C １ -C ６ Alkoxy, halogenated C １ -C ６ Alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, linear or branched C １ -C ５ Alkyl or halogenated C １ -C ５ 4. The compound of claim 3, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, characterized in that one or more substituents are selected from the group consisting of alkyl.

12. L ３ , R ａ２ are each independently 【Chemistry 9】 selected from the group consisting of: Here, X ６ is deuterium, halogen, nitro, cyano, hydroxy, mercapto, C １ -C ６ Alkoxy, halogenated C １ -C ６ Alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, linear or branched C １ -C ６ Alkyl or halogenated C １ -C ６ selected from the group consisting of alkyl; m is an integer of 0, 1, 2, 3, 4, or 5, and when m is an integer of 2, 3, 4, or 5, each X6 is the same or different; X ７ , X ９ are each independently selected from CH or N; Each X ８ are each independently selected from the group consisting of O, S, or NH; R １７ is hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, C １ -C ６ Alkoxy, halogenated C １ -C ６ Alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, linear or branched C １ -C ５ Alkyl or halogenated C １ -C ５ alkyl, wherein preferably halogenated C １ -C ６ 12. The compound or a salt, enantiomer, stereoisomer, polymorph or solvate thereof according to claim 3 or 11, characterized in that alkoxy is selected from trifluoromethoxy.

13. The chemical structure of the compound is as follows:

2. The compound according to claim 1, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, which is any one selected from the group consisting of:

14. 14. The compound of formula I according to any one of claims 1 to 13, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, which is a hydrohalide (including hydrochloride and hydrobromide), sulfate, citrate, maleate, methanesulfonate, citrate, lactate, L-tartrate, fumarate, L-malate, phosphate, dihydrogen phosphate, pyrophosphate, metaphosphate, oxalate, malonate, benzoate, mandelate, succinate, trifluoroacetate, hippurate, hydroxyacetate, or p-toluenesulfonate salt of the compound of formula I.

15. 1. A compound of formula A or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, [Chemistry 18] Formula A In Formula A, X is CO or CH ２ Selected from: L １ is selected from S or O; X １ is selected from the group consisting of substituted or unsubstituted straight or branched chain alkylene, or X １ does not exist; X ａ has the structure of formula A1: 【Chemistry 19】 Formula A1 In formula A1, Ring C is selected from the group consisting of substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, substituted or unsubstituted heterocyclylene, or substituted or unsubstituted cycloalkylene, and w represents an integer of 0 or 1; and Ring D represents a substituted or unsubstituted nitrogen-containing heterocyclyl; R ａ is selected from the group consisting of deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, halogenated alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R ｂ１ , R ｂ２ , R ｂ３ , R ｂ４ and R ｂ５ are each independently selected from the group consisting of hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, alkoxy, halogenated alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted straight or branched chain alkyl; and n represents an integer of 0, 1, 2, or 3, and when n represents an integer of 2 or 3, each R ａ are the same or different, compounds of formula A or salts, enantiomers, stereoisomers, polymorphs or solvates thereof.

16. X １ is a substituted or unsubstituted straight or branched chain C １ -C ５ represents alkylene, or X １ does not exist; and / or X ａ has the structure of formula A1: 【Chemistry 20】 Formula A1 In formula A1, Ring C is a substituted or unsubstituted C ５ -C ３０ arylene, substituted or unsubstituted 5- to 30-membered heteroarylene, substituted or unsubstituted 4- to 30-membered heterocyclylene, or substituted or unsubstituted C ３ -C ３０ cycloalkylene; preferably, ring C is selected from the group consisting of substituted or unsubstituted C ５ -C ２０ arylene, substituted or unsubstituted 5- to 20-membered heteroarylene, substituted or unsubstituted 4- to 20-membered heterocyclylene, or substituted or unsubstituted C ３ -C ２０ cycloalkylene; w represents an integer of 0 or 1; and Ring D represents a substituted or unsubstituted 4- to 30-membered nitrogen-containing heterocyclyl; preferably, Ring D represents a substituted or unsubstituted 4- to 20-membered nitrogen-containing heterocyclyl; and / or R ａ is deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, C １ -C ６ Alkoxy, halogenated C １ -C ６ Alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted straight or branched chain C １ -C ５ Alkyl, substituted or unsubstituted C ３ -C １５ Cycloalkyl, substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted C ５ -C １５ aryl, or substituted or unsubstituted 5- to 15-membered heteroaryl; preferably, R ａ is deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, C １ -C ６ Alkoxy, trifluoromethoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted straight or branched chain C １ -C ５ Alkyl, substituted or unsubstituted C ３ -C １５ Cycloalkyl, substituted or unsubstituted 4- to 15-membered heterocyclyl, substituted or unsubstituted C ５ -C １５ aryl, or substituted or unsubstituted 5-15 membered heteroaryl; and / or R ｂ１ , R ｂ２ , R ｂ３ , R ｂ４ and R ｂ５ are each independently hydrogen, deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, C １ -C ６ Alkoxy, halogenated C １ -C ６ Alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, or substituted or unsubstituted straight or branched chain C １ -C ５ alkyl; preferably, R ｂ１ , R ｂ２ , R ｂ３ , R ｂ４ and R ｂ５ are each independently hydrogen, deuterium, F, Cl, Br, I, nitro, cyano, hydroxy, mercapto, C １ -C ６ Alkoxy, trifluoromethoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, or substituted or unsubstituted straight or branched chain C １ -C ５ 16. The compound of formula A according to claim 15, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, characterized in that: is selected from the group consisting of alkyl.

17. X １ represents methylene, ethylene, propylene or isopropylene, or X １ 16. The compound of formula A according to claim 15, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein: is absent.

18. X ａ has the structure of formula A1: 【Chemistry 21】 Formula A1 represents In formula A1, the ring C is a substituted or unsubstituted C ５ -C １５ arylene, substituted or unsubstituted 5- to 15-membered heteroarylene, substituted or unsubstituted 4- to 15-membered heterocyclylene, or substituted or unsubstituted C ３ -C １５ cycloalkylene, wherein the substituents of said substituted ring C are optionally selected from the group consisting of halogen, mercapto, hydroxy, amino, cyano, C １ -C ６ Alkyl, C １ -C ６ Alkoxy, halogenated C １ -C ６ one or more substituents selected from the group consisting of alkyl, aryl, arylsulfonyl ... w represents an integer of 0 or 1; and 16. The compound of formula A according to claim 15, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, wherein ring D represents a substituted or unsubstituted 4-15 membered nitrogen-containing heterocyclyl.

19. (1) The ring C is one of the following groups: Azetidinylene, oxetanylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, dihydropyranylene, tetrahydrothienylene, tetrahydrothiopyranylene, oxazolidinylene, thiazolidinylene, piperidinylene, piperazinylene, morpholinylene, thiomorpholinylene, dioxacyclohexylene, dioxacyclohexenylene, azacyclohepta annylene, azacyclooctylene, diazacycloheptanylene, diazacyclooctylene, bridged heterocyclylene (e.g., a 5- to 15-membered bridged heterocyclylene, such as azabicyclohexylene, azabicycloheptanylene, or azabicyclooctylene), or spiroheterocyclylene (e.g., a 5- to 15-membered spiroheterocyclylene, such as 3-azaspiro[5.5]undecanylene or 7-azaspiro[3.5]nonanylene); or Furanylene, oxazolylene, isoxazolylene, oxadiazolylene, thienylene, thiazolylene, isothiazolylene, thiadiazolylene, pyrrolylene, imidazolylene, pyrazolylene, triazolylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, isoindolylene, benzofuranylene, isobenzofuranylene, benzothienylene, indazolylene, benzimidazolylene, benzoxazolylene, benzo isoxazolylene, benzothiazolylene, benzisothiazolylene, benzotriazolylene, benzo[2,1,3]oxadiazolylene, benzo[2,1,3]thiadiazolylene, benzo[1,2,3]thiadiazolylene, quinolinylene, isoquinolinylene, naphthyridinylene, cinnolinylene, quinazolinylene, quinoxalinylene, phthalazinylene, pyrazolo[1,5-a]pyridylene, pyrazolo[1,5-a]pyrimidinylene, imidazo[1,2a]pyridylene, 1H-pyrrolo[3,2-b]pyridylene, 1H-pyrrolo[2,3-b]pyridylene, pyrrolo[2,1-b]thiazolylene and imidazo[2,1-b]thiazolylene; or Cyclopropylene, cyclobutylene, cyclopentylene, cyclopentenylene, cyclohexylene, cyclohexenylene, cycloheptylene, cyclooctylene, decalinylene, octahydrocyclopentalenylene, octahydro-1H-indenylene, spirocycloalkylene (e.g., C ５ -C １５ spirocycloalkylene, for example spiro[3.3]heptylene, spiro[2.5]octylene, spiro[3.5]nonylene, spiro[4.4]nonylene, spiro[4.5]decylene, or spiro[5.5]undecylene), or bridged cycloalkylene (for example, C ５ -C １５ a bridged cycloalkylene, such as adamantanylene, noradamantanylene, bornylene, biscyclo[2.2.1]heptylene, 2-oxobiscyclo[2.2.1]heptylene, or biscyclo[2.2.1]heptenylene; or selected from the group consisting of phenylene or naphthylene; wherein the ring C may further optionally be deuterium, halogen, nitro, mercapto, hydroxy, cyano, C １ -C ６ Alkyl, C １ -C ６ Alkoxy, halogenated C １ -C ６ Alkoxy, halogenated C １ -C ６ substituted with one or more substituents selected from the group consisting of alkyl, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, or any combination thereof; and / or (2) said Ring D is selected from the group consisting of the following groups: azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidyl, oxazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, azacycloheptanyl, azacyclooctyl, diazacycloheptanyl, diazacyclooctyl, nitrogen-containing bridged heterocyclyl (e.g., a 5- to 15-membered bridged heterocyclyl, such as azabicyclohexyl, azabicycloheptanyl, or azabicyclooctyl), or nitrogen-containing spiroheterocyclyl (e.g., a 5- to 15-membered spiroheterocyclyl, such as 3-azaspiro[5.5]undecanyl or 7-azaspiro[3.5]nonanyl); wherein the ring D may further optionally be a deuterium, a halogen, a nitro, a mercapto, a hydroxy, a cyano, an oxo group, C １ -C ６ Alkyl, C １ -C ６ Alkoxy, halogenated C １ -C ６ Alkoxy, halogenated C １ -C ６ 16. The compound of formula A according to claim 15, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, characterized in that it is substituted with one or more substituents selected from the group consisting of alkyl, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, or any combination thereof.

20. X ａ teeth, 【Chemistry 22】 selected from the group consisting of: Here, R ｄ１ , R ｄ２ are each independently hydrogen, deuterium, halogen, nitro, cyano, hydroxy, mercapto, C １ -C ６ Alkoxy, halogenated C １ -C ６ Alkoxy, substituted or unsubstituted amino, substituted or unsubstituted silyl, substituted or unsubstituted boryl, substituted or unsubstituted straight or branched chain C １ -C ５ alkyl; and R ｄ１ , R ｄ２ 16. The compound of formula A according to claim 15, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, characterized in that: is not simultaneously hydrogen.

21. 3-(5-(azetidin-3-ylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-(pyrrolidin-3-ylthio)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-(piperidin-4-ylthio)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-(azepan-4-ylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(azetidin-3-ylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(azetidin-3-ylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(azetidin-3-ylthio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-azaspiro[3.5]nonan-2-yl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-azaspiro[5.5]undecan-9-yl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((octahydrocyclopenta[c]pyrrol-5-yl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,3-difluoropiperidin-4-yl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-azabicyclo[3.2.0]heptan-6-yl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-azabicyclo[3.1.0]hexane-6-yl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((3-azabicyclo[3.1.1]heptan-1-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(((5-(azetidin-3-yl)pyridin-3-yl)methyl)thio)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-(azetidin-3-yloxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-(pyrrolidin-3-yloxy)isoindolin-2-yl)piperidine-2,6-dione; 3-(1-oxo-5-(piperidin-4-yloxy)isoindolin-2-yl)piperidine-2,6-dione; 3-(5-(azepan-4-yloxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(4-(azetidin-3-yloxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(6-(azetidin-3-yloxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(7-(azetidin-3-yloxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((7-azaspiro[3.5]nonan-2-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((octahydrocyclopenta[c]pyrrol-5-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-azaspiro[5.5]undecan-9-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3,3-difluoropiperidin-4-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-azabicyclo[3.2.0]heptan-6-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-azabicyclo[3.1.0]hexane-6-yl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 3-(5-((3-azabicyclo[3.1.1]heptan-1-yl)methoxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; and 16. The compound of formula A according to claim 15, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, characterized in that it is selected from the group consisting of 3-(5-((5-(azetidin-3-yl)pyridin-3-yl)methoxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione.

22. 22. The compound of formula A according to any one of claims 15 to 21, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, which is a hydrohalide (including hydrochloride and hydrobromide), sulfate, citrate, maleate, methanesulfonate, citrate, lactate, L-tartrate, fumarate, L-malate, phosphate, dihydrogen phosphate, pyrophosphate, metaphosphate, oxalate, malonate, benzoate, mandelate, succinate, trifluoroacetate, hippurate, hydroxyacetate, or p-toluenesulfonate salt of the compound of formula A.

23. A compound according to any one of claims 1 to 14 or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, and at least one pharmaceutically acceptable carrier or excipient; or A compound of formula A according to any one of claims 15-22 or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, and at least one pharmaceutically acceptable carrier or excipient; and optionally at least one additional therapeutic agent, such as an anti-cancer agent.

24. A compound according to any one of claims 1 to 14 or a pharmaceutically acceptable salt thereof; or A compound of formula A according to any one of claims 15 to 22 or a pharmaceutically acceptable salt thereof; or A pharmaceutical or reagent kit comprising the pharmaceutical composition of claim 23.

25. 15. A compound according to any one of claims 1 to 14, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, for use as a medicament.

26. A compound of formula A according to any one of claims 15 to 22 or a salt, enantiomer, stereoisomer, polymorph or solvate thereof for use as a medicament.

27. 27. A compound of claim 25, or a compound of formula A of claim 26, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, for use in treating a cereblon protein-related disease or condition.

28. Use of a compound according to any one of claims 1-14, or a compound of formula A according to any one of claims 15-22, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, or a pharmaceutical composition according to claim 23, in the manufacture of a medicament for treating a disease or condition associated with a cereblon protein.

29. A method for treating or preventing a cereblon protein-associated disease or condition, comprising administering to a subject a therapeutically effective amount of a compound of any one of claims 1-14, or a compound of formula A of any one of claims 15-22, or a salt, enantiomer, stereoisomer, polymorph or solvate thereof, or a pharmaceutical composition of claim 23.

30. The compound, use or method according to any one of claims 27 to 29, wherein the cereblon protein-associated disease or condition is selected from the group consisting of tumors, infectious diseases, inflammatory diseases, immune system diseases, anemia, hemorrhagic shock, transplant rejection, multiple organ dysfunction syndrome, sarcoidosis, adult respiratory distress syndrome, cardiovascular diseases, Richter syndrome (RS), acute liver failure or diabetes.

31. The cereblon protein-associated diseases or conditions include bone marrow aneurysms (e.g., multiple myeloma, plasma cell myeloma, smoldering myeloma, smoldering multiple myeloma); myelofibrosis; bone marrow disorders; myelodysplastic syndromes; previously treated myelodysplastic syndromes; transplant-associated cancers; neutropenia; leukemias (e.g., acute myeloid leukemia, chronic granulocytic leukemia, B-cell chronic lymphocytic leukemia, leukemia-associated anemia, acute myeloid leukemia, monocytic leukemia, acute lymphocytic leukemia (ALL), acute B-cell lymphoblastic leukemia, acute T-cell lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, and the like). lymphomas (e.g., diffuse large B-cell lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, anaplastic lymphoma, anaplastic large cell lymphoma, CD20-positive lymphoma, mantle cell lymphoma, follicular lymphoma (FL), Burkitt's lymphoma, primary lymphoma, B-cell lymphoma, recurrent B-cell non-Hodgkin's lymphoma, recurrent diffuse large B-cell lymphoma, recurrent mediastinal (thymic) large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, recurrent transformation Refractory transformed non-Hodgkin's lymphoma, refractory B-cell non-Hodgkin's lymphoma, refractory diffuse large B-cell lymphoma, refractory primary mediastinal (thymic) large B-cell lymphoma, refractory transformed non-Hodgkin's lymphoma; thyroid cancer; melanoma; lung cancer (e.g., lung adenocarcinoma, lung squamous cell carcinoma, non-small cell lung carcinoma, and small cell lung carcinoma); inflammatory myofibroblastic tumor; colorectal cancer; intestinal cancer; brain glioma; astroblastoma; glioma; peripheral neuroepithelioma; ovarian cancer; bronchogenic carcinoma; prostate cancer; breast cancer (e.g., triple-negative breast cancer, incidental breast cancer, and Cowden's disease); pancreatic Cancer; central nervous system cancer; neuroblastoma; extramedullary plasmacytoma; plasmacytoma; gastric cancer; gastrointestinal stromal tumor; esophageal cancer; colorectal adenocarcinoma; esophageal squamous cell carcinoma; liver cancer; renal cell carcinoma; bladder cancer; endometrial cancer; uterine cancer; head and neck cancer; brain cancer; oral cancer; sarcoma (including, for example, rhabdomyosarcoma, various lipogenic tumors, Ewing's sarcoma / primitive neuroectodermal tumor, and leiomyosarcoma); urothelial carcinoma; basal cell carcinoma; oral squamous cell carcinoma; bile duct cancer; bone cancer; cervical cancer; skin cancer; bone tumor; brain tumor; lung or mesothelial tumor; colon tumor; ureter tumor; Richter syndrome (RS); pyogenic syndrome;Autoimmune diseases (e.g., rheumatoid arthritis, autoimmune encephalomyelitis, ankylosing spondylitis, psoriasis, systemic lupus erythematosus, multiple sclerosis, recurrent oral ulcers, Kawasaki disease, polymyositis / dermatomyositis, Sjogren's syndrome, atopic dermatitis, vitiligo, experimental autoimmune encephalomyelitis, including Arthus reaction); keratoconjunctivitis sicca; inflammatory diseases (e.g., Crohn's disease and ulcerative colitis, pneumonia, osteoarthritis, synovitis, systemic inflammatory response syndrome, airway inflammation, bronchitis, rheumatoid spondylitis, gouty arthritis, eczema, psoriasis, dermatitis, uveitis, conjunctivitis, acute respiratory distress syndrome, bacteremia, endotoxemia, stomatitis, gingivitis, pancreatitis, regional ileitis, atrophic gastritis, peritonitis, peptic ulcer, or irritable bowel syndrome (IBS).

31. The compound, use, or method of claim 30, wherein the compound is selected from the group consisting of: cerebral malaria; infectious diseases (e.g., viral pneumonia, AIDS, COVID-19, gram-negative bacterial infections, gram-positive bacterial infections, tuberculosis); septic shock; tuberculosis; bacterial meningitis; chronic obstructive pulmonary disease; asthma; hemorrhagic shock; organ or tissue transplant rejection (kidney, heart, lung, or tissue transplant rejection); diabetes; sarcoidosis; adult respiratory distress syndrome; anemia; pediatric aplastic anemia; cardiovascular diseases (e.g., coronary heart disease, congestive heart failure, myocardial infarction, atherosclerosis); multiple organ failure due to cachexia and septic shock; or acute liver failure.

32. 23. Use of a compound of formula A according to any one of claims 15 to 22, or a salt, enantiomer, stereoisomer, polymorph, or solvate thereof, for the manufacture of a cereblon protein (CRBN) binding agent.

33. 23. Use of a compound of formula A, or a salt, enantiomer, polymorph or solvate thereof, according to any one of claims 15 to 22, for use in the preparation of a compound, or a salt, enantiomer, polymorph or solvate thereof, according to claim 1.

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