Compounds for use in the prevention or treatment of a lipid metabolism related disease

Abstract

The present application relates to the field of biological medicine, and in particular to a "LC3-binding moiety-lipid droplet-binding moiety-conjugate" formed by covalently linking a structure capable of binding LC3 and a structure capable of binding lipid droplets together, a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopically-substituted compound, metabolite or prodrug thereof, and use in the preparation of a medicament for preventing or treating a disease related to lipid metabolism.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, and more particularly to compounds of formula (I), pharmaceutically acceptable salts, stereoisomers, solvates, polymorphs, tautomers, isotopic compounds, metabolites or prodrugs, and their use in the preparation of medicaments for the prevention or treatment of lipid metabolism-related diseases. Background Technology

[0002] Lipid droplets (LDs), also known as liposomes, are conserved organelles present in all cells, storing neutral lipids within the cell. The composition of neutral lipids may vary in different tissues, but they are primarily triglycerides and sterol esters. Lipid droplets are highly dynamic organelles that not only store neutral lipids but also participate in various physiological and pathological processes, such as metabolic disorders, immune responses, and pathogen infections. Their quantity and level are associated with various diseases; many common metabolic diseases, such as metabolic syndrome and obesity, often lead to abnormal accumulation of lipid droplets in non-adipose tissues. For example, abnormal accumulation of lipid droplets in the liver is also known as hepatic steatosis. New evidence suggests that intracellular lipid droplet (LD) deposition is involved in lipid toxicity and precedes neurodegeneration.

[0003] Many diseases are caused by excessively high levels of lipid droplets in specific cells or tissues. For such diseases, a common treatment strategy is to reduce lipid or lipid droplet levels. Currently, many methods for controlling lipid or lipid droplet levels are still in the basic research stage and have poor specificity. Therefore, a feasible treatment strategy is to control lipid or lipid droplet levels using compounds that reduce the number and size of lipid droplets (hereinafter referred to as compounds).

[0004] Therefore, there is an urgent need in the field for effective compounds that can be used to treat or prevent lipid droplet-related diseases. Summary of the Invention

[0005] In one aspect, the present invention provides compounds of formula (I), or pharmaceutically acceptable salts, stereoisomers, solvates, polymorphs, tautomers, isotopic compounds, metabolites, or prodrugs thereof.

[0006] LCM―L―TM (I)

[0007] in:

[0008] LCM is the LC3 bonding portion;

[0009] L represents the connector section;

[0010] TM represents the lipid droplet binding region.

[0011] The LCM portion is the part that has an affinity for the LC3 protein, and the TM portion is the part that can interact non-covalently with lipid droplets.

[0012] In another aspect, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite, or prodrug thereof, or the use of a pharmaceutical composition of the present invention in the preparation of a medicament for treating lipid metabolism-related diseases. In one embodiment, the lipid metabolism-related diseases are selected from MADD, obesity, NAFLD, type II diabetes, hepatocellular carcinoma, Alzheimer's disease, and atherosclerosis.

[0013] In another aspect, the present invention provides a method for preparing the compounds of the present invention, comprising: covalently linking a structure capable of binding LC3 with a structure capable of binding lipid droplets, thereby forming an "LC3-binding portion-lipid droplet-binding portion coupling" ("coupling compound").

[0014] In another aspect, the present invention provides a method for reducing intracellular lipid droplets, comprising contacting a coupling compound comprising an LC3-binding portion and a lipid droplet-binding portion with cells or tissues containing lipid droplets, wherein the lipid droplets are contained in the cells under physiological or pathological conditions, and / or are induced to form in the cells. In one embodiment, the coupling compound is a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite, or prodrug thereof. Attached Figure Description

[0015] In the attached figures, C1 represents compound 1A, C2 represents compound 2A, C3 represents compound 3A, C4 represents compound 4A, C5 represents compound 5A, C6 represents compound 6, C7 represents compound 7, C8 represents compound 8, C9 represents compound 9, C10 represents compound 10A, C11 represents compound 11A, and OA represents sodium oleate. SIV or ORBB represents Sudan IV (Oil Red BB), SIII represents Sudan III, GW5074 represents compound A1, DP or AN2 represents compound A5, and Linker represents 10-bromo-1-decyl alcohol.

[0016] Figure 1 Compound 1A 1 H NMR and 1 H- 1 H NOESY spectrum. Among them... 1 H- 1 The two intersecting auxiliary lines and the auxiliary circle at the intersection in the H NOESY spectrum show the correlation signals between Ha and Hb in the graph.

[0017] Figure 2 Compound 2A 1 H NMR and 1H- 1 H NOESY spectrum. Among them... 1 H- 1 The two intersecting auxiliary lines and the auxiliary circle at the intersection in the H NOESY spectrum show the correlation signals between Ha and Hb in the graph.

[0018] Figures 3 to 12 : NMR spectra of compounds 3A, 4A, 5A, 6, 7, 8, 9, 10A, 10B and 11A, respectively.

[0019] Figure 13 Representative diagrams of lipid droplet induction (green: lipid droplets; blue: cell nuclei) in wild-type, Atg5 knockout MEF cells, and SH-SY5Y cells. Compound concentrations are shown in the figure. Treatment time was 24 h. Lipid droplets were induced using... 493 / 503 staining, scale bar = 50 μm.

[0020] Figure 14 Extracellular oleic acid (OA) treatment induces lipid droplets. BODIPY493 / 503 staining images show the staining results of cells induced with OA for 6 hours and the control without OA.

[0021] Figure 15 (A) Uncoupled LC3-binding compounds or lipid droplet-binding compounds do not affect BODIPY signal. (B) No decrease in lipid droplet signal was observed when lipid droplets in OA-induced SH-SY5Y cells were stained with BODIPY in the presence of 50 μM Sudan IV. (C) BODIPY493 / 503 staining results of lipid droplets in OA-induced cells treated with uncoupled LC3-binding compounds or lipid droplet-binding compounds.

[0022] Figure 16A Left image: Representative illustration of compound 1A reducing lipid droplet-induced lipid droplet formation in wild-type MEF cells (green: lipid droplets; blue: cell nuclei). Compound concentrations are shown in the figure. Treatment time was 24 h. Lipid droplets were... 493 / 503 staining, scale bar = 50 μm. Right figure: Statistical analysis of lipid droplet number and size changes (n = 8 for each concentration). Statistical analysis was performed using one-way ANOVA and Dunnett's post-hoc analysis comparing with the DMSO group.

[0023] Figure 16B Left image: Representative diagram of compound 2A reducing lipid droplet-induced lipid droplets in wild-type MEF cells (green: lipid droplets; blue: cell nuclei). Compound concentrations are shown in the figure. Treatment time: 24 h. Lipid droplets were... 493 / 503 staining, scale bar = 50 μm. Right figure: Statistical analysis of lipid droplet number and size changes (n = 9 for each concentration). Statistical analysis was performed using one-way ANOVA and Dunnett's post-hoc analysis comparing with the DMSO group.

[0024] Figure 17 Left image: Representative illustration showing that compounds 1A and 2A do not reduce lipid droplets (green: lipid droplets; blue: nuclei) in autophagy-deficient MEF cells. Treatment with compounds 1A or 2A (concentrations shown in the figure) did not alter the autophagy-deficient MEF (Atg5) cell type. - / - Cellular lipid droplet levels, compound treatment time 24 h, lipid droplets used 493 / 503 staining, scale bar = 50 μm. Right figure: Statistical analysis of lipid droplet number and size changes (n = 6 for each concentration). Statistical analysis was performed using one-way ANOVA and Dunnett's post-hoc analysis comparing with the DMSO group.

[0025] Figure 18A and Figure 18B Compound 1A ( Figure 18A ) and compound 2A ( Figure 18B Representative diagram (left) and quantitative analysis (right) of lipid droplets (green: lipid droplets; blue: nuclei) in SH-SY5Y cells. Autophagy was induced by starvation with EBSS for 4 h (EBSS) or inhibited by treatment with 5 mM NH4Cl, significantly reducing or slightly increasing lipid droplet levels, respectively. Treatment with compound 1A or compound 2A (concentrations shown in the figure) significantly reduced lipid droplet levels in SH-SY5Y cells. The treatment time was 24 h, and lipid droplets were... 493 / 503 staining, scale bar = 50 μm. Right figure: Statistical analysis of lipid droplet number and size changes (n = 9 for each concentration). Statistical analysis was performed using one-way ANOVA and Dunnett's post-hoc analysis comparing with the DMSO group.

[0026] Figure 19 Left image: Representative illustration showing that compounds 1A and 2A did not reduce lipid droplet levels in SH-SY5Y cells (green: lipid droplets; blue: nuclei) in the presence of the autophagy inhibitor NH4Cl (5mM). Treatment with either compound 1A or compound 2A (concentrations shown in the figure) along with NH4Cl (5mM) did not alter lipid droplet levels in SH-SY5Y cells. The treatment time was 24 hours. (The text then repeats the last sentence about lipid droplet levels.) 493 / 503 staining, scale bar = 50 μm. Right figure: Statistical analysis of lipid droplet number and size changes (n = 6 for each concentration). Statistical analysis was performed using one-way ANOVA and Dunnett's post-hoc analysis comparing with the DMSO group.

[0027] Figure 20A and Figure 20B Compounds in SH-SY5Y cells ( Figure 20A ) and wild-type MEF cells ( Figure 20B Representative diagram (left) and quantification (right) of the effect of compound on OA-induced lipid droplets (green: lipid droplets; blue: cell nuclei). Compound concentrations are shown in the figure. Treatment time was 24 h. Lipid droplets were... 493 / 503 staining, scale bar = 50 μm. Right figure: Statistical analysis of changes in lipid droplet number and size (Figure A: n = 9 per concentration; Figure B: n = 6 per concentration). Statistical analysis was performed using one-way ANOVA and Dunnett's post-hoc analysis comparing with the DMSO group. Uncoupled LC3-binding compounds or lipid droplet probes did not reduce the number and nucleus size of lipid droplets in SH-SY5Y or MEF cells.

[0028] Figure 21 The image above shows a representative view of adipocytes differentiated from 3T3-L1 adipocyte precursor cells (green: lipid droplets; blue: nucleus) without induction. The compound significantly reduced lipid droplets in WAC. Treatment with 5 mM NH4Cl to inhibit autophagy resulted in a slight increase in lipid droplets, while other control compounds had no effect on lipid droplets. The compound treatment time was 24 h, and lipid droplets were... 493 / 503 staining, scale bar = 50 μm. Right figure: Statistical analysis of lipid droplet number and size changes (n = 15). Statistical analysis was performed using one-way ANOVA and Dunnett's post-hoc analysis comparing with the DMSO group.

[0029] Figure 22 MST was used to measure the affinity interactions between the coupling compound Kd and LC3B, including Sudan III, Sudan IV, and LC3B. No affinity was observed between the lipid droplet probe and LC3B in the sub-micromolar to micromolar range for the coupling compound Kd.

[0030] Figure 23 Left: Schematic diagram of a method for measuring ternary complex formation using an improved ELISA; Right: ELISA signal of the sample after blank correction (n=3).

[0031] Figure 24 Left image: Aggregates (red) of the autophagosome marker protein LC3B indicated by mCherry show autophagosomes. 493 / 503 staining indicates lipid droplets (green), and DAPI indicates cell nuclei (blue). The average size of lipid droplets is larger than that of autophagosomes. The proportion of red overlapping or closely adhering to green indicates colocalization of autophagosomes with lipid droplets. Right figure: Percentage of lipid droplets in the sample colocalized with autophagosomes. Experimental results are from two independent transfection batches. Analysis was performed using one-way ANOVA and Dunnett's post-hoc analysis compared with the DMSO group.

[0032] Figure 25 Lipid droplets in wild-type and LC3B knockout HEK293T cells were treated with the compound. BODIPY493 / 503 staining was performed. Scale bar: 20 μm.

[0033] Figure 26 The compound did not affect the level of autophagy. (A) In MEF cells transfected with mCherry-LC3B treated with the compound, the number of LC3B signal spots did not change. (B) Lysotracker staining showed no change in the number of lysosomes. (C) MEF cells transfected with mRFP-GFP-LC3B treated with the compound or starved (replaced with EBSS for 4 hours). Color: Only red dots represent autolysosomes, and yellow dots represent autophagosomes. Autolysosomes (ALYS; red) were observed. + ,green - ) / Autophagosomes (APHG; Red) + ,green + The ratio of ( ) remained unchanged, indicating that the compound had no effect on autophagy flux. (D) Western blot analysis showed that LC3B and SQSTM1 / p62 levels in MEF cells treated with the compound remained unchanged, LC3-II indicated autophagosomes, and Tubulin was used as the internal control. Statistical results are shown in the figure below. Statistical analysis was performed using one-way ANOVA and Dunnett's post-hoc analysis comparing the results with the DMSO group.

[0034] Figure 27 (AB) Representative staining images (from >3 replicates) show that the compound did not damage the nuclear membrane (A, Lamin B1 immunostaining) or cell membrane (B, CellMask). TM (C) Red indicates healthy mitochondria (MitoTracker) TM Red: Green indicates total mitochondria (MitoTracker) TM Green). For each hole, the total red. + green + The ratio of area to green+ area indicates the proportion of healthy mitochondria, representing the integrity of the mitochondrial membrane.

[0035] Figure 28 Representative diagram (n=6) of endogenous lipid droplets (green: lipid droplets; blue: nuclei) in the normal human hepatocyte cell line QSG7701 under non-induction conditions. Compounds 1A and 2A significantly reduced lipid droplets in WAC. Treatment with 5 mM NH4Cl to inhibit autophagy resulted in a slight increase in lipid droplets. Other control compounds had no effect on lipid droplets. Treatment time was 24 h. Lipid droplets were... 493 / 503 staining, scale bar = 50 μm. Due to the scarcity and small size of endogenous lipid droplets in this hepatocyte line, accurate statistical analysis was impossible, therefore no statistical results were obtained.

[0036] Figure 29 The image above shows how the compound reduces lipid droplet induction in wild-type MEF cells. The compound concentration was 5 μM, the treatment time was 24 h, and the lipid droplets were... 493 / 503 staining, scale bar = 50 μm. Left, right, and bottom panels: statistical analysis of lipid droplet number and size changes, and results of measuring cellular TAG levels. Statistical analysis employed one-way ANOVA and Dunnett's post-hoc analysis comparing with the DMSO group.

[0037] Figure 30 (A) Left panel: Body weight (measured daily and normalized to the mean body weight on day 0), Middle panel: Body fat / lean body mass ratio (after 12 days of injection) and liver weight (after 14 days of injection, endpoint measurement). (B) Endpoint measurement of liver triglyceride (TAG) and total cholesterol (TC) levels (after 14 days of injection). (C) Serum triglyceride (TAG) and total cholesterol (TC) levels in db / db mice at different time points after injection. (D) Endogenous lipid droplets in liver sections stained with BODIPY493 / 503 from mice 14 days after injection. For statistical analysis, images from at least 3 sections were averaged for each mouse. (E) Absolute quantitative lipidomics of the livers of db / db mice (4 mice per group). Left panel: Lipid concentrations in the samples, shown in log10. Darker red or brighter green indicates lower concentrations. Cyan dashed boxes indicate several key areas. DMSO data are placed in the middle for comparison. Right figure: Log2 FC of different lipids (X-axis) compared to DMSO. A few lipids with extremely low abundance (total concentration <1 μg / g) were ignored. The area of ​​each symbol represents the abundance of lipids in the DMSO group. Red indicates significant changes (absolute log2 FC value > 0.6, p < 0.05, verified by a two-tailed unpaired t-test). For measurements at multiple time points, statistical analysis employed two-way ANOVA and Dunnett's post-hoc analysis comparing with the DMSO group. For endpoint measurements across multiple groups, one-way ANOVA and Dunnett's post-hoc analysis comparing with the DMSO group were used.

[0038] Figure 31 (A) Measurement of compound 3A concentration in liver and plasma samples collected at specified time points after intraperitoneal injection of compound 3A (30 mg / kg). (B) Body weight, serum TC, and TAG levels in db / db mice injected with and without DMSO. The results showed that DMSO did not decrease these parameters; on the contrary, it caused a slight increase in serum TAG. The DMSO group and... Figure 25 The same groups were used. (C) A similar experiment was conducted in NASH mice to (B). Here, the DMSO group was the same as... Figure 33 The same groups are used here. (D) Weight-normalized food and water intake, which is the same as... Figure 25 , Figure 30 The same groups are shown. The WT_DMSO group is identical to the Chow_DMSO group. Note that in db mice, compounds 4A and 3A resulted in a slightly significant increase, rather than a decrease, in body weight-normalized food and water intake. Serum (E) and endpoint liver (F) free fatty acid (FFA) levels are shown for the groups (EF). Figure 25 , Figure 30 The same groups are displayed. For measurements at multiple time points, statistical analysis was performed using two-way ANOVA and Dunnett's post-hoc analysis comparing with the DMSO group. For endpoint measurements in multiple groups, one-way ANOVA and Dunnett's post-hoc analysis comparing with the DMSO group were performed.

[0039] Figure 32 Typical lipid analysis of the liver based on lipidomics data. (A) ChE, TAG, PE, or PI levels for different fatty acid chain carbon numbers (chain carbon number #). The numbers in parentheses indicate the overall change in mouse liver samples treated with the compound compared to the DMSO control.

[0040] Figure 33 (A) Left panel: Body weight (measured daily and normalized to the mean body weight on day 0); Middle panel: Body fat / lean body mass ratio (after 12 days of injection) and liver weight (measured at the endpoint after 14 days of injection). (B) Endpoint measurements of liver triglyceride (TAG) and total cholesterol (TC) levels (after 14 days of injection). (C) Serum triglyceride (TAG) and total cholesterol (TC) levels in NASH mice at different time points after injection. (D) Endogenous lipid droplets in mouse liver sections stained with BODIPY493 / 503 14 days after injection, scale bar = 50 μm. (E) Interstitial fibrosis in mouse liver samples assessed by pico-sirius staining 14 days after injection. (Red) + Area relative to green +Area was normalized to assess the degree of liver fibrosis. For measurements at multiple time points, statistical analysis was performed using two-way ANOVA and Dunnett's post-hoc analysis comparing with the DMSO group. For endpoint measurements across multiple groups, one-way ANOVA and Dunnett's post-hoc analysis comparing with the DMSO group were used. Detailed Implementation

[0041] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In case of any conflict, the definitions provided herein shall prevail. When trade names appear herein, they are intended to refer to the corresponding product or its active ingredient. All patents, published patent applications, and publications cited herein are incorporated herein by reference.

[0042] General terms and definitions

[0043] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In case of any conflict, the definitions provided herein shall prevail. When trade names appear herein, they are intended to refer to the corresponding product or its active ingredient. All patents, published patent applications, and publications cited herein are incorporated herein by reference.

[0044] The terms “comprising,” “including,” “having,” “containing,” or “involving,” and their other variations herein, are inclusive or open-ended and do not exclude other elements or method steps not listed. Those skilled in the art will understand that the foregoing term “comprising” encompasses the meaning of “consisting of.”

[0045] The term "one or more species" or similar expression "at least one species" can mean, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more species.

[0046] When the lower and upper limits of a numerical range are disclosed, any numerical value falling within that range and any included range are specifically disclosed. In particular, each range of values ​​disclosed herein should be understood as representing each numerical value and range encompassed within a wider range.

[0047] The expression "mn" as used in this article refers to the range from m to n, the subranges consisting of individual point values, and the individual point values ​​themselves. For example, the expression "C1-C8" or "C1-8" covers the range of 1 to 8 carbon atoms and should be understood to also cover any subranges and individual point values ​​within it, such as C2-C5, C3-C4, C1-C2, C1-C3, C1-C4, C1-C5, C1-C6, C1-C7, etc., and C1, C2, C3, C4, C5, C6, C7, C8, etc. For example, the expression "C3-C 10 "or "C 3-10 "It should also be understood in a similar way, for example, it can cover any subrange and point value contained therein, such as C3-C9, C6-C9, C6-C8, C6-C7, C7-C..." 10 C7-C9, C7-C8, C8-C9, etc., as well as C3, C4, C5, C6, C7, C8, C9, C 10 For example, the expression "three to ten yuan" should be understood as encompassing any subrange and each point value within it, such as three to five yuan, three to six yuan, three to seven yuan, three to eight yuan, four to five yuan, four to six yuan, four to seven yuan, four to eight yuan, five to seven yuan, five to eight yuan, six to seven yuan, six to eight yuan, nine to ten yuan, etc., as well as three, four, five, six, seven, eight, nine, ten yuan, etc. Other similar expressions in this article should also be understood in a similar manner.

[0048] The term “optional” or “optionally” means that the event or situation described below may or may not occur, including both the occurrence and non-occurrence of the event or situation.

[0049] The terms "substitution" and "substituted" refer to the selective replacement of one or more (e.g., one, two, three, or four) hydrogen atoms on a specified atom by a designated group, provided that the substitution does not exceed the normal valence of the specified atom in the present case and that the substitution forms a stable compound. Combinations of substituents and / or variables are permitted only if such combinations form a stable compound. When describing the absence of a substituent, it should be understood that the substituent can be one or more hydrogen atoms, provided that the structure allows the compound to reach a stable state.

[0050] When each carbon atom in the descriptive group can be optionally replaced by a heteroatom, the condition is that the valence of all atoms in the group is not exceeded in the present case, and a stable compound is formed.

[0051] If a substituent is described as "optionally...substituted", then the substituent may be unsubstituted or may be substituted. If an atom or group is described as being optionally substituted by one or more of the substituents in the list, then one or more hydrogen atoms on that atom or group may be substituted by independently selected, optional substituents. When the substituent is oxo (i.e., =O), it means that two hydrogen atoms are substituted.

[0052] Unless otherwise specified, as used herein, the connection point of a substituent may be any suitable location of the substituent. When the bond of a substituent is such that it is a bond that passes through the ring and connects two atoms, such a substituent may be bonded to either cyclic atom in the substituted ring.

[0053] When any variable (e.g., R), and variables with labels (e.g., R) X1 R X2 R X3 R 2 R 7 R 8 R a1 R b1 R c1 R a2 R b2 R c2 R 19 R E R F R G R a R b R c R d When a group (e.g., R) appears more than once in the composition or structure of a compound, its definition is independent in each instance. For example, if a group is substituted by 0, 1, 2, 3, or 4 R substituents, the group may optionally be substituted by up to four R substituents, and the options for each R substituent in each instance are independent of each other.

[0054] The terms “halogen” or “halogenated” should be understood to refer to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I) atoms, preferably fluorine, chlorine or bromine atoms.

[0055] The term "alkyl" refers to a straight-chain or branched saturated aliphatic hydrocarbon group consisting of carbon and hydrogen atoms, connected to the rest of the molecule by single bonds. Alkyl groups can have 1-8 carbon atoms, i.e., "C1-C8 alkyl", such as C1-4 alkyl, C1-3 alkyl, C1-2 alkyl, C3 alkyl, C4 alkyl, C1-6 alkyl, C... 3-6Alkyl. Non-limiting examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl, or 1,2-dimethylbutyl, or their isomers. A "subunit" is a group obtained by removing a hydrogen atom from a carbon atom containing a free valence electron, having two connection sites for attachment to the rest of the molecule. For example, "alkylene" or "alkyl subunit" refers to a saturated straight-chain or branched divalent hydrocarbon group. When the described groups are linked together, it should be understood that the number of connection sites for each linked group increases. For example, if an alkyl group is further linked to other groups to give the alkyl group two connection sites, the alkyl group can be considered to have formed an alkylene group.

[0056] The term "alkylene," when used alone or in combination with other groups herein, refers to a straight-chain or branched saturated divalent hydrocarbon group. For example, the term "C 1-8 "Alkylene" refers to alkylene groups having 1-8 carbon atoms, such as methylene, ethylene, propylene, butylene, pentylene, hexylene, 1-methylethylene, 2-methylethylene, methylpropylene, or ethylpropylene. The term "cycloalkylene" refers to a cyclic, saturated divalent hydrocarbon group. For example, the term "C..." 3-6 "Cycloalkylene" refers to cycloalkyl subunits having 3-6 carbon atoms, such as cyclopropyl subunits, cyclobutyl subunits, cyclopentyl subunits, cyclohexyl subunits, etc. The term "alkoxy subunit" refers to "-O-alkylene" or "alkylene-O-". "C 1-8 Examples of "alkoxy subunits" include, but are not limited to, -O-methylene, -O-ethylene, -O-propylene, -O-butylene, methylene-O-, ethylene-O-, propylene-O-, butylene-O-, etc.

[0057] The term "alkenyl" refers to an unsaturated aliphatic hydrocarbon group consisting of a straight or branched chain of carbon and hydrogen atoms, with at least one double bond. Alkenyl groups can have 2-8 carbon atoms, i.e., "C6H ... 2-8 "Alkenyl", for example, C 2-4 alkenyl, C 3-4Alkenyl. Non-limiting examples of alkenyl groups include, but are not limited to, vinyl, allyl, (E)-2-methylvinyl, (Z)-2-methylvinyl, (E)-but-2-enyl, (Z)-but-2-enyl, (E)-but-1-enyl, (Z)-but-1-enyl, etc. When an alkenyl group is further linked to other groups to provide two linkage sites, the alkenyl group can be considered to form an alkenyl subunit.

[0058] The term "alkynyl" refers to a straight-chain or branched unsaturated aliphatic hydrocarbon group consisting of carbon and hydrogen atoms, with at least one triple bond. Alynyl groups can have 2-8 carbon atoms, i.e., "C6H ... 2-8 "Alkyne group", such as C 2-4 alkynyl group, C 3-4 Alkyne group. Non-limiting examples of alkynyl groups include, but are not limited to, ethynyl, prop-1-alkynyl, prop-2-alkynyl, but-1-alkynyl, but-2-alkynyl, but-3-alkynyl, etc. When an alkynyl group is further linked to other groups to give the alkynyl group two linkage sites, the alkynyl group can be considered to form an alkynyl subunit.

[0059] The term "cyclic hydrocarbon group" refers to a saturated or unsaturated non-aromatic cyclic hydrocarbon group composed of carbon and hydrogen atoms, preferably containing one or two rings. The cyclic hydrocarbon group can be a monocyclic, fused polycyclic, bridged, or spirocyclic structure. The cyclic hydrocarbon group can have 3-10 carbon atoms, i.e., "C 3-10 "Cyclic hydrocarbon group", such as C 3-8 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon groups, C5 cyclic hydrocarbon groups, C6 cyclic hydrocarbon groups, and C7 cyclic hydrocarbon groups. Non-limiting examples of cyclic hydrocarbon groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclic [2.2.1]heptyl, and spiro[3.3]heptyl. The term also covers cases where the C atom can be substituted with an oxygen (=O). When a cyclic hydrocarbon group is further linked to other groups to give the cyclic hydrocarbon group two linkage sites, the cyclic hydrocarbon group can be considered to form a subcyclic hydrocarbon group.

[0060] The term "cycloalkyl" refers to a saturated cycloalkyl group. A "cycloalkyl" group can have 3-10 carbon atoms, i.e., "C60"... 3-10 "Cycloalkyl", for example, C 3-8 cycloalkyl, C 3-6 Cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C7 cycloalkyl. When a cycloalkyl group is further linked to other groups to give the cycloalkyl group two linkage sites, the cycloalkyl group can be considered to form a cycloalkylene group.

[0061] The term "heterocyclic group" or "heterocyclic hydrocarbon group" refers to a monocyclic or bicyclic cyclic system (ternary to decacyclic, ternary to octagonal, ternary to heptary, quaternary to hexacyclic) having, for example, 3 to 10 (suitably 3 to 8, more preferably 3 to 7, especially 4 to 6) ring atoms, wherein at least one ring atom (e.g., 1, 2, or 3) is a heteroatom selected from N, O, S, and P, and the remaining ring atoms are C. The cyclic system can be saturated (or understood as the corresponding "heterocyclic alkyl") or unsaturated (i.e., having one or more double and / or triple bonds within the ring). "Heterocyclic group" or "heterocyclic hydrocarbon group" is not aromatic. The term also covers cases where the C atom can be substituted with an oxo (=O) and / or the S atom on the ring can be substituted with one or two oxo (=O) atoms and / or the P atom on the ring can be substituted with one or two oxo (=O) atoms. When a heterocyclic group is further linked to other groups to give the heterocyclic group two connection sites, the heterocyclic group can be considered to form a heterocyclic subunit.

[0062] The heterocyclic group can be, for example, a four-membered ring, such as azahexacyclobutane or oxacyclobutane; or a five-membered ring, such as tetrahydrofuranyl, dioxolinyl, pyrrolyl, imidazoalkyl, pyrazolyl, pyrrolinyl, oxopyrrolyl, or 2-oxoimidazolidin-1-yl; or a six-membered ring, such as tetrahydropyranyl, piperidinyl, morpholinyl, dithiaalkyl, thiomorpholinyl, piperazine, 1,1-dioxo-1,2-thiazin-2-yl, or trithiaalkyl; or a seven-membered ring, such as diazacyclobutane. The heterocyclic group may optionally be benzofused.

[0063] Heterocyclic groups can be bicyclic, without limitation, such as five-membered fused five-membered rings, such as hexahydrocyclopentane[c]pyrrole-2(1H)-yl ring; or five-membered fused six-membered bicyclic rings, such as hexahydropyrrolo[1,2-a]pyrazine-2(1H)-yl ring.

[0064] As mentioned above, heterocycles can be unsaturated, meaning they can contain one or more double bonds without limitation. For example, unsaturated heterocycles containing nitrogen atoms can be 1,6-dihydropyrimidine, 1,2-dihydropyrimidine, 1,4-dihydropyrimidine, 1,6-dihydropyridine, 1,2-dihydropyridine, 1,4-dihydropyridine, 2,3-dihydro-1H-pyrrole, 3,4-dihydro-1H-pyrrole, 2,5-dihydro-1H-pyrroleyl, 4H-[1,3,4]thiadiazinyl, 4,5-dihydrooxazolyl, or 4H-[1,4]thiazinyl rings. Unsaturated heterocycles containing oxygen atoms can be 2H-pyran, 4H-pyran, or 2,3-dihydrofuran. Unsaturated heterocycles containing sulfur atoms can be 2H-thiaran or 4H-thiaran. Heterocycles can be benzofused without limitation, such as dihydroisoquinoline rings.

[0065] The term "aryl" refers to an aromatic ring group consisting of an all-carbon monocyclic or fused polycyclic (e.g., bicyclic) ring with a conjugated π-electron system. For example, an aryl group can have 6-14 carbon atoms, suitably 6-10, and more preferably 6 or 10. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, and anthracene. When an aryl group is further linked to other groups to provide two linkage sites, the aryl group can be considered to have formed an aryl subunit.

[0066] The term "heteroaryl" should be understood to preferably refer to a monovalent monocyclic, bicyclic, or tricyclic aromatic ring system having 5, 6, 7, 8, 9, or 10 ring atoms ("pentacyclic to decacyclic heteroaryl"), particularly 5, 6, 9, or 10 ring atoms, and the ring atoms contain at least one (suitably 1-4, more preferably 1, 2, or 3) heteroatoms that may be the same or different, said heteroatoms being, for example, oxygen, nitrogen, or sulfur. Furthermore, in each case, the heteroaryl group may be benzofused. Specifically, the heteroaryl group is selected from thienyl, furanyl, pyrroleyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, etc., and their benzo[derivatives], such as benzofuranyl, benzothienyl, benzooxazolyl, benzoisooxazolyl, benzoimidazolyl, benzotriazolyl, indazole, indolyl, isindolyl, etc.; or pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, etc., and their benzo[derivatives], such as quinolinyl, quinazolinyl, isoquinolinyl, etc.; or azocinyl, inazinyl, purinyl, etc., and their benzo[derivatives]; or cyclophosphinyl, phthalazinyl, quinazolinyl, quinoxolinyl, naphridinyl, carbazole, acridinyl, etc. When a heteroaryl group is further linked to other groups to give the heteroaryl group two linkage sites, the heteroaryl group can be considered to form a heteroaryl subunit.

[0067] The term "hydrocarbon chain" refers to a chain-like group composed of carbon and hydrogen atoms, which can be straight or branched. The hydrocarbon chain can be saturated (i.e., alkylene) or unsaturated, meaning it can contain one or more (preferably one) carbon-carbon double or triple bonds. Non-limiting examples of alkylene groups include, but are not limited to, methylene (-CH2-), 1,1-ethylene (-CH(CH3)-), 1,2-ethylene (-CH2CH2-), 1,1-propylene (-CH(CH2CH3)-), 1,2-propylene (-CH2CH(CH3)-), 1,3-propylene (-CH2CH2CH2-), 1,4-butylene (-CH2CH2CH2CH2-), and 1,7-heptene (-CH2CH2CH2CH2CH2CH2-).

[0068] In this text, when describing chemical bonds connecting a molecule or a part of a molecule, if the specific atoms connected by the chemical bonds are not described, it means that the chemical bond can connect to any atom of the molecule or the part of the molecule, as long as a stable structure can be formed. For example, a part of the molecule can be described and placed in brackets, such as parentheses or square brackets; when describing other parts of the molecule connected to the part in brackets by chemical bonds, if the specific atoms connected by the chemical bonds in the brackets are not described, it means that the chemical bond can connect to any atom of the part in the brackets, as long as a stable structure can be formed.

[0069] The term "pharmaceutical acceptable" means that, within the bounds of normal medical judgment, contact with a patient's tissues will not cause undue toxicity, irritation, allergic reactions, etc., and that the benefits and risks are reasonable and that the product is effective for its intended use.

[0070] Pharmaceutically acceptable salts of the compounds of the present invention include their acid addition salts and base addition salts. Suitable acid addition salts are formed by acids that form pharmaceutically acceptable salts. Examples include hydrochlorides, acetates, aspartates, benzoates, bicarbonates / carbonates, glucono-p-glucose, gluconates, nitrates, orotates, palmitates, and other similar salts. Suitable base addition salts are formed by bases that form pharmaceutically acceptable salts. Examples include aluminum salts, arginine salts, choline salts, magnesium salts, and other similar salts. Methods for preparing pharmaceutically acceptable salts of the compounds of the present invention are known to those skilled in the art.

[0071] The compounds of this invention can exist in specific geometric or stereoisomeric forms. This invention contemplates all such compounds, including cis and trans isomers, (-)- and (+)- enantiomers, (R)- and (S)- enantiomers, diastereomers, (D)- isomers, (L)- isomers, and racemic mixtures thereof, as well as other mixtures, such as mixtures enriched with enantiomers or diastereomers, all of which are within the scope of this invention. Additional asymmetric carbon atoms may be present in substituents such as alkyl groups. All such isomers and mixtures thereof are included within the scope of this invention. In some embodiments, the preferred compounds are those isomers exhibiting superior biological activity. Purified or partially purified isomers and stereoisomers of the compounds of this invention, or racemic mixtures or diastereomer mixtures, are also included within the scope of this invention. Purification and separation of such substances can be achieved using standard techniques known in the art.

[0072] Optically pure enantiomers can be obtained by resolving racemic mixtures using conventional methods, such as by forming diastereomer salts using optically active acids or bases, or by forming covalent diastereomers. Mixtures of diastereomers can be separated into individual diastereomers based on their physical and / or chemical differences using methods known in the art (e.g., by chromatography or fractional crystallization). An optically active enantiomer base or acid is then released from the separated diastereomer salt. Another method for separating racemic enantiomers uses chiral chromatography (e.g., chiral HPLC columns), where the separated chiral isomers may be conventionally derivatized or not derivatized prior to separation, depending on which method allows for more efficient separation of the chiral isomers. Enzymatic methods can also be used to separate derivatized or underivatized chiral isomers. Similarly, optically pure compounds of the present invention can be obtained via chiral synthesis using optically active starting materials.

[0073] Furthermore, the compounds of the present invention can exist in the form of tautomers. The present invention includes all possible tautomers of the compounds of the present invention, as well as single tautomers or any mixtures of said tautomers in any proportion.

[0074] The compounds of the present invention can exist in the form of solvates (preferably hydrates), wherein the compounds of the present invention contain a polar solvent, particularly, for example, water, methanol, or ethanol, as a structural element of the lattice of the compound. The amount of the polar solvent, particularly water, can be stoichiometric or non-stoichiometric.

[0075] This invention also covers all possible crystalline forms or polymorphs of the compounds of this invention, which may be a single polymorph or a mixture of more than one polymorph in any proportion.

[0076] The present invention also includes all pharmaceutically acceptable isotopically labeled compounds that are identical to the compounds of the present invention, except that one or more atoms are replaced by atoms having the same atomic number but with an atomic mass or mass number different from the dominant atomic mass or mass number in nature.

[0077] The scope of this invention also includes metabolites of the compounds of this invention, i.e., substances formed in the body upon administration of the compounds of this invention. Metabolites of the compounds can be identified using techniques known in the art, and their activity can be characterized by experimental methods. Such products can be generated, for example, by oxidation, reduction, hydrolysis, amidation, deamidation, esterification, enzymatic hydrolysis, etc., of the administered compound. Therefore, this invention includes metabolites of the compounds of this invention, including compounds obtained by methods that expose the compounds of this invention to mammals for a time sufficient to produce their metabolites.

[0078] This invention further includes, within its scope, prodrugs of the compounds of this invention, which are certain derivatives of the compounds of this invention that may themselves have little or no pharmacological activity, and which, when administered to or onto the body, can be converted, for example, by hydrolysis and cleavage into the compounds of this invention having the desired activity. Typically, such prodrugs are functional group derivatives of the compounds that are readily converted in vivo into the compounds with the desired therapeutic activity. For a review of prodrugs and methods of their preparation, see, for example, J. Rautio et al., Nature Reviews Drug Discovery (2008) 7, 255-270 and Prodrugs: Challenges and Rewards (V. Stella et al. ed., Springer, 2007). The prodrugs of this invention can be prepared, for example, by replacing suitable functional groups present in the compounds of this invention with certain portions known to those skilled in the art as “pro-moiety.”

[0079] The term “polymorph” or “polymorphic material” refers to a single polymorph or a mixture of more than one polymorph in any proportion.

[0080] The term "crystal form" or "crystal" refers to any solid substance that exhibits a three-dimensional arrangement, as opposed to amorphous solid substances, and produces characteristic X-ray powder diffraction patterns with clearly defined peaks.

[0081] The term "amorphous" refers to any solid substance that is not ordered in three dimensions.

[0082] The term "hydrate" describes a solvate containing a drug with stoichiometric or non-stoichiometric amounts of water.

[0083] The term "pharmaceutically acceptable carrier" refers to substances that do not cause significant irritation to the organism and do not impair the biological activity and properties of the active compound. "Pharmaceutically acceptable carriers" include, but are not limited to, flow aids, sweeteners, diluents, preservatives, dyes / colorants, flavoring agents, surfactants, wetting agents, dispersants, disintegrants, stabilizers, solvents, or emulsifiers. Non-limiting examples of such carriers include calcium carbonate, calcium phosphate, various sugars and starches, cellulose derivatives, gelatin, vegetable oils, and polyethylene glycol.

[0084] The terms "administration" or "giving" refer to methods that enable the delivery of a compound or composition to a desired biological site of action. These methods include, but are not limited to, oral or parenteral administration (including intraventricular, intravenous, subcutaneous, intraperitoneal, intramuscular, and intravascular injection or infusion), local administration, and rectal administration. In particular, injection or oral administration.

[0085] As used herein, the term "treatment" includes relieving, reducing, or improving a disease or symptom; preventing other symptoms; improving or preventing underlying metabolic factors of symptoms; inhibiting a disease or symptom, for example, preventing the development of a disease or symptom; reducing a disease or symptom; promoting the remission of a disease or symptom; or causing the symptom of a disease or symptom to cease; and extends to include prevention. "Treatment" also includes achieving therapeutic and / or preventive benefits. A therapeutic benefit refers to the eradication or improvement of the condition being treated. Furthermore, a therapeutic benefit is achieved by eradicating or improving one or more physical symptoms associated with an underlying disease, and an improvement in the patient's condition can be observed even though the patient may still have the underlying disease. A preventive benefit refers to the use of a composition by a patient to prevent the risk of a certain disease, or the use by a patient when experiencing one or more physical symptoms of a disease, even though the disease has not yet been diagnosed.

[0086] The terms “active ingredient,” “therapeutic agent,” “active substance,” or “active agent” refer to a chemical entity that can effectively treat or prevent a target disorder, disease, or symptom.

[0087] For the purposes of pharmaceuticals, pharmaceutical units, or active ingredients, the terms "effective amount," "therapeutic effective amount," or "preventive effective amount" refer to a sufficient quantity of a drug or agent that provides acceptable side effects while achieving the desired therapeutic effect. The determination of the effective amount varies from person to person, depending on the individual's age and general condition, as well as the specific active substance. The appropriate effective amount in a given case can be determined by a person skilled in the art based on routine testing.

[0088] As used herein, “individual” includes both human and non-human animals. Exemplary human individuals include human individuals suffering from a disease (such as the disease described herein) (referred to as patients) or normal individuals. In this invention, “non-human animals” includes all vertebrates, such as non-mammals (e.g., birds, amphibians, reptiles) and mammals, such as non-human primates, livestock, and / or domesticated animals (e.g., sheep, dogs, cats, cows, pigs, etc.).

[0089] Lipid droplets (LDs) are conserved organelles within cells that store neutral lipids. The surface of lipid droplets is covered by a single phospholipid membrane, upon which lipid droplet proteins are embedded. The composition of neutral lipids stored in lipid droplets may vary in different tissues, but is primarily composed of triglycerides and sterol esters. Depending on the cell type, some other endogenous neutral lipids (such as retinyl esters, ether lipids, and free cholesterol) may also be stored in LDs. Major proteins on the surface of lipid droplets include, for example, the Perilipin family of proteins (PAT family proteins), whose members include: Perilipin1, Perilipin2 (PLIN2, also known as Adipophilin or ADRP), Perilipin3 (PLIN3, also known as TIP47), Perilipin4 (PLIN4, also known as S3-12), and Perilipin5 (PLIN5, or OXPAT / LSDP5).

[0090] The term "lipid" refers to organic compounds that possess lipophilic or amphiphilic properties. In this document, it specifically refers to lipophilic organic compounds present in living organisms. Lipid molecules containing acidic groups such as carboxyl, phosphate / phosphate ester, or sulfonic acid groups are acidic lipids; examples include, but are not limited to, fatty acids and phospholipids. Lipid molecules without acidic groups are neutral lipids; examples include, but are not limited to, triglycerides, steroids (e.g., sterols), steroid esters (e.g., sterol esters), ether lipids, and neutral glycolipids. Examples of sterols include, but are not limited to, cholesterol. Examples of ether lipids include, but are not limited to, alkylglycerols (AKG) and alkyl-phospholipids. In this document, neutral lipids specifically refer to those stored in lipid droplets.

[0091] The term "steroid," also known as a steroidal body, refers to a derivative of cyclopentanoperhydrophenanthrene. The term "sterol" refers to a steroid containing a hydroxyl group, also known as a sterol. Sterols are preferably steroids containing 3-OH, such as cholesterol (also known as cholesterol steroid).

[0092] The term "steroid ester" or "sterol ester" refers to an ester formed from a steroid (sterol, also known as a steroidal alcohol) containing a hydroxyl group and an acid, particularly an ester formed from a fatty acid. Examples of steroid esters include, but are not limited to, cholesterol esters, such as cholesterol oleate, linoleate, etc.

[0093] The term "lipophilic probe" refers to known small molecules used to indicate lipid droplets. Some lipid droplet probes can be detected by optical signals under suitable conditions. The optical signal can be fluorescence, with wavelengths in the visible light region or invisible to the naked eye, such as infrared, near-infrared, etc. Preferably, the "lipophilic probe" is more likely to partition in lipids than in the aqueous phase. It should be understood that for some environmentally sensitive probes, although they emit a stronger signal in a lipophilic environment, this does not necessarily mean that they are more likely to partition in lipids.

[0094] The terms "lipid-binding structure," "lipid-binding compound," and "lipid-binding moiety" refer to structures, compounds, or molecular parts capable of binding lipid droplets, and preferably selectively binding lipid droplets in cells. Lipid-binding compounds, as used herein, include known lipid drop probes, compounds capable of binding lipid drop-labeled proteins, or compounds capable of binding neutral lipids in lipid droplets. Lipid drop-labeled proteins include, but are not limited to, Perilipin2 (PLIN2, also known as Adipophilin or ADRP, PMID: 30351430) and Perilipin3 (PLIN3, also known as TIP47, PMID: 25961502). Compounds capable of binding neutral lipids in lipid droplets include, but are not limited to, steroids and steroid esters. Lipid drop probes include, but are not limited to, lipid drop-specific probes and probes that preferentially target lipid droplets in cells, preferably lipid drop-specific probes. Examples of lipid droplet probes include, but are not limited to, lipophilic dye molecules that are affinity for lipid droplets, such as those reported by Fam, et al. ("Recent Advances in Fluorescent Probes for Lipid Droplets." Materials (2018), 11, 1768): lipid droplet-affinity azo dyes (such as Sudan I, Sudan II, Sudan III, Oil Red BB (also known as Sudan IV), Oil Red O (also known as Sudan 5B), Sudan Red G, Sudan Black B (also known as Solvent Black 3), Nile Red). 493 / 503, Monodanthyl pentane (compatible in multicolor, MDH), PyrPy 10d, PyrPy11c, PITE (pyroindole-tetraphenylethylene hybrid), TPE-AmAl, TPA-BI, LipidGreen, LipidGreen2, LD540, AF8, AF10, AFN, NAP AIEgen dyes (e.g., NAP-Ph, NAP-Br, NAP-CF3, NAP-Py), LD-BTD1, LipiDye, Phos 2a, Phos 2b, Phos 3a, Phos 3b, SF44, SF58, FAS, DPAS, BTD-coumarin hybrids (e.g., BTD-Lip), IND-TPA, photoactivated AIE probes (e.g., BZT 3a, BZT 4a), LD-TPZn, LQD, photoactivated AIEgen probes (e.g., PhotoAFN) 2a-c), TPE-AC, TPMN, TTMN, MeTTMN, MeOTTMN, DCMa, DCI, DCFu, NLV-1, StatoMerocynaine dyes (SMCy dyes, such as SMCy 3, SMCy 5.5).

[0095] LC3 protein refers to the microtubule-associated protein 1 light chain 3 (MAP1LC3, LC3) family within the Atg8 protein family. LC3 protein specifically refers to the following members of the human LC3 family: human microtubule-associated protein 1 light chain 3α (MAP1LC3A, LC3A, e.g., see Uniprot Accession: Q9H492-1 and Q9H492-2), human microtubule-associated protein 1 light chain 3β (MAP1LC3B, LC3B, e.g., see Uniprot Accession: Q9GZQ8) or human microtubule-associated protein 1 light chain 3γ (MAP1LC3C, LC3C, e.g., see Uniprot Accession: Q9BXW4), particularly LC3A and LC3B, especially LC3B.

[0096] LC3 proteins, such as LC3A, LC3B, and LC3C, can be located on the membranes of pre-autophagosomes and autophagosomes, and are key proteins in the autophagy process.

[0097] The forms of LC3 proteins that can be used include, for example, LC3-I and LC3-II, but are not limited to these. Specifically, the LC3 proteins that can be used include, but are not limited to, LC3A-I, LC3A-II, LC3B-I, LC3B-II, LC3C-I or LC3C-II, preferably LC3A-II, LC3B-I or LC3B-II, especially LC3B-I or LC3B-II.

[0098] In this paper, homologs of the LC3 protein may be used, as long as they can be used in the methods of the present invention, for example, interacting with lipid droplets.

[0099] The homologs of the LC3 protein used in this article can be derived from eukaryotes, such as yeast, or from other non-human animals, such as insects (e.g., fruit flies), fish, rodents, even-toed ungulates, and primates. Homologs of the LC3 protein can also be derived from other proteins with similar structures and functions, such as GABARAPL1, but are not limited to these. For example, see GABARAPL1 (Uniprot Accession: O95166) and GABARAPL1 (Uniprot Accession: Q9H0R8-1 and Q9H0R8-2), but are not limited to these.

[0100] In this document, fragments of the LC3 protein or its homologs may also be used, provided they are suitable for use in the methods of the present invention, such as interacting with lipid droplets. Such fragments may, for example, have 25% or more, 30% or more, 35% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, or 100% identity with the LC3 protein or its homologs.

[0101] The objectives of this invention can be achieved using proteins or fragments thereof that have the same or similarity to the LC3 protein or its homologs, as long as they are usable in the methods of this invention. For example, such interactions with lipid droplets. For example, such similarity can be 25% or higher, 30% or higher, 35% or higher, 40% or higher, 50% or higher, 60% or higher, 70% or higher, 80% or higher, 90% or higher, 95% or higher, or 100%.

[0102] In an exemplary embodiment, the LC3 protein or its homologs, or fragments thereof, has 25% or more, 30% or more, 35% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, or 100% sequence identity with any of the amino acid sequences in SEQ ID NO:1 to SEQ ID NO:4. Those skilled in the art will understand that this also means that the LC3 protein or its homologs, or fragments thereof, used may contain such sequences.

[0103] Those skilled in the art will also understand that modified or mature forms of LC3 protein or its homologs or fragments thereof can be used. For example, in some cases, amino acids 121-125 at the C-terminus of LC3 protein such as LC3A (e.g., SEQ ID NO:1 or SEQ ID NO:2), LC3B (e.g., SEQ ID NO:3), or LC3C (e.g., SEQ ID NO:4) are cleaved. For example, in some cases, after the C-terminal amino acids are cleaved, the LC3 protein is lipidized to form a phosphatidylethanolamine (PE) modified form. Such a scheme is also within the scope of the LC3 protein described in this invention.

[0104] Those skilled in the art will understand that the LC3 protein or its homologs or fragments thereof can be modified or altered as needed for use in this invention. Such modifications or alterations are also covered within the scope of this invention. Such modifications or alterations may include, but are not limited to, adding tags (such as GST or HIS) or labeling, or substituting, deleting, adding, or replacing certain amino acids. For example, for ease of tag cutting, the end of the sequence in SEQ ID NO:3 can be slightly modified or altered; for example, the M at the N-terminus of SEQ ID NO:3 can be replaced with GG, and then optionally a tag such as GST can be added to the modified or unmodified sequence for use in this invention. Such modified or altered sequences, or sequences having 25% or higher, 30% or higher, 35% or higher, 40% or higher, 50% or higher, 60% or higher, 70% or higher, 80% or higher, 90% or higher, 95% or higher, or 100% sequence identity, are also within the scope of this invention.

[0105] The term "affinity activity screening" refers to the process of detecting the affinity binding between a sample and a target. Detection methods used in affinity activity screening can include, for example, absorbance methods, radiometric methods (e.g., proximity scintillation analysis), fluorescence methods (e.g., fluorescence resonance energy transfer, fluorescence polarization detection, especially time-correlated fluorescence techniques), chemiluminescence methods (e.g., amplified chemiluminescence affinity homogeneous detection, ALPHAScreen), surface plasmon resonance (SPR, which can be implemented, for example, using GE's Biacore series), isothermal titration calorimetry (ITC), micro-thermophoresis (MST), or oblique incidence reflectance method.

[0106] As used herein, “sequence identity” between two amino acid sequences refers to the percentage of identical amino acids between the sequences. “Sequence homology” refers to the percentage of identical or conserved amino acid substitutions. For sequence comparisons, typically one sequence is used as a reference sequence against which the test sequence is compared. When using a sequence comparison algorithm, the test and reference sequences are input into the computer, and subsequence coordinates and sequence algorithm program parameters are specified if necessary. Based on the specified program parameters, the sequence comparison algorithm calculates the percentage of sequence identity of the test sequence relative to the reference sequence. Examples of algorithms suitable for determining sequence identity and sequence similarity percentages include, but are not limited to, the BLAST and BLAST 2.0 algorithms. Software for performing BLAST analysis is available from the National Center for Biotechnology Information (NCBI).

[0107] The terms "small molecule compound," "organic small molecule," or "low molecular weight compound" refer to molecules whose size is comparable to that of organic molecules commonly used in pharmaceuticals. This term excludes biological macromolecules (such as proteins and nucleic acids), but covers small molecular weight proteins or their derivatives, such as dipeptides, tripeptides, tetrapeptides, and pentapeptides.

[0108] As used herein, the term "binding" refers to covalent or non-covalent interaction. Examples of covalent binding include, but are not limited to, covalent binding via orthogonal organic chemical reactions, such as the Click reaction. Preferably, "LC3 binding" refers to an affinity for the LC3 protein (also known as binding affinity), and "lipid droplet binding" refers to a non-covalent interaction with a lipid droplet or a component constituting the lipid droplet. Examples of non-covalent interactions include: affinity interactions, ion-pair interactions, electrostatic interactions involving dipoles, hydrogen bonds, π effects, induced dipole interactions, and hydrophobic effects.

[0109] Affinity can be detected by any known method. For example, it can be a parameter that measures the binding strength between the analyte molecule and the LC3 protein or its homologs or fragments thereof. Depending on the binding assay performed, the aforementioned “parameter” can be varied, but in particular it can be, for example, absorbance value, radioactivity signal and / or its distribution in the sample, fluorescence signal intensity and / or its distribution in the sample, thermal changes, reflected light intensity, reflected light phase changes, etc.

[0110] Non-covalent interactions can be detected by any known method. For example, parameters such as the binding strength of the analyte to neutral lipids can be determined, or its distribution in a sample can be measured. Some methods can be used to predict or infer the distribution of molecules in samples containing neutral lipids, such as determining the solubility of molecules in neutral lipids under suitable conditions, or determining the partitioning of molecules between an aqueous phase and an oil phase formed from neutral lipids under suitable conditions.

[0111] The terms “LC3 binding structure,” “LC3 binding compound,” and “LC3 binding moiety” refer to the structural, compound, or molecular part that can bind LC3 protein or its homologs or fragments thereof.

[0112] The term "coupling," or "linking," or the "connection" of the LC3-binding moiety with the lipid droplet-binding moiety, refers to the covalent connection of structures with specific functions. For example, the expression "LC3-binding moiety coupled with lipid droplet-binding moiety" means covalently connecting a structure capable of binding LC3 with a structure capable of binding lipid droplets, thereby forming an "LC3-binding moiety-lipid droplet-binding moiety-coupling compound," which is also referred to as a "coupling compound" in this document. "Uncoupled" indicates that the LC3-binding compound is not covalently connected to the lipid droplet-binding moiety, or vice versa.

[0113] The term "lipid metabolism-related diseases" refers to diseases caused by lipid metabolism disorders and / or hyperlipidemia, particularly those caused by lipid metabolism disorders (e.g., neutral lipid metabolism disorders). Lipid metabolism-related diseases include, but are not limited to, diseases associated with abnormal accumulation of lipid droplets.

[0114] The term "disorders associated with abnormal lipid droplet accumulation" refers to diseases caused by the abnormal accumulation of lipid droplets in somatic cells or diseases characterized by abnormal enrichment of lipid droplets during their course. Individuals at risk of developing disorders associated with abnormal lipid droplet accumulation can be identified by detecting triglyceride or sterol levels in tissues. Triglycerides and sterols are stored within the lipid droplets discussed herein. Tissues or tissue-based cellular samples can be detected using histochemical methods, such as Oil Red O staining / BODIPY (e.g., ...). 493 / 503 staining, or detection by triglyceride or sterol kits (e.g., commercially available kits). In mouse models of non-alcoholic fatty liver disease (NAFLD), DAG and ceramide levels are elevated in hepatocytes, heart, and muscle LD. Examples of diseases associated with abnormal lipid droplet accumulation include, but are not limited to, neutral lipid storage disease (NLSD), multiple acyl-CoA dehydrogenase deficiency (MADD) in mutant lymphoblasts, obesity, intrahepatic lipid deposition (also known as hepatic steatosis, such as NAFLD, particularly non-alcoholic steatohepatitis (NASH)), type II diabetes, hepatocellular carcinoma, Alzheimer's disease, and atherosclerosis. Examples of NLSD include, but are not limited to, NLSD I (Chanarin-Dorfman syndrome) and neutral lipid storage disease with myopathy (NLSDM).

[0115] Examples of diseases associated with abnormal lipid droplet accumulation include cholesterol ester storage disease (CESD), familial hypercholesterolemia, metabolic syndrome, and stroke. "Conditions associated with abnormal lipid droplet accumulation" encompass the symptoms of these diseases, as well as other pathological conditions or symptoms caused by abnormal lipid accumulation. Secondary hyperlipidemia or dyslipidemia caused by various diseases can produce "lipotoxicity" in organs, cells, or tissues; these are also included in conditions associated with abnormal lipid droplet accumulation.

[0116] The basic mechanisms of autophagy are classified into three different types: macroautophagy, molecular chaperone-mediated autophagy (CMA), and microautophagy. As used herein, "autophagy" is not specifically limited to macroautophagy, CMA, or microautophagy. Preferably, "autophagy" refers to macroautophagy. Macroautophagy is not specifically limited to selective macroautophagy or non-selective macroautophagy. Some literature refers to the macroautophagic form of lipids as lipophagy, or simply lipophage. Some literature suggests that lipophage can selectively recognize lipids. Lipophagy is encompassed within the scope of "autophagy" as described herein.

[0117] The following detailed description of the invention is intended to illustrate non-limiting embodiments, enabling other skilled in the art to more fully understand the technical solutions, principles, and practical applications of the invention, so that other skilled in the art can modify and implement the invention in many forms to best suit the requirements of a particular application.

[0118] The compounds of the present invention

[0119] In one aspect, the present invention provides compounds of formula (I), or pharmaceutically acceptable salts, stereoisomers, solvates, polymorphs, tautomers, isotopic compounds, metabolites, or prodrugs thereof.

[0120] LCM―L―TM(I)

[0121] in:

[0122] LCM is the LC3 bonding portion;

[0123] L represents the connector section;

[0124] TM represents the lipid droplet binding region.

[0125] In one embodiment, the LCM portion and the TM portion are each independently selected from small molecule compounds. In a specific embodiment, the molecular weight of the LCM portion and the TM portion are each independently about 100 to about 2000 Da, preferably about 200 to about 1000 Da, for example about 200 to about 900 Da, about 200 to about 800 Da, about 200 to about 700 Da, about 200 to about 600 Da, or about 200 to about 500 Da.

[0126] In an alternative embodiment, the TM portion binds to lipid droplet-associated targets. The lipid droplet-associated targets are components of the lipid droplet, preferably selected from neutral lipids and lipid droplet-labeling proteins. In one embodiment, the neutral lipids are selected from triglycerides and cholesterol esters. In one embodiment, the lipid droplet-labeling proteins are selected from Perilipin family proteins (e.g., Perilipin 1, Perilipin 2, and Perilipin 3). In yet another embodiment, the lipid droplet-labeling proteins are those detectable by commercially available antibodies against lipid droplet-labeling proteins.

[0127] In another alternative embodiment, in the compound of formula (I), the LCM moiety can be linked to one or more TM moietyes, or vice versa. When more than one TM moiety exists, the TM moiety can be selected independently, and the individual TM moiety can be the same or different. In one embodiment, multiple TM moiety targeting the same target exist. It should be understood that even for the same target, multiple identical or different TM moiety can be used in a coupling compound as needed. When more than one TM moiety is used, the connectors L used can also be selected independently. The target of the TM moiety is a lipid droplet-related target.

[0128] In one embodiment, the LCM portion interacts with the LC3 protein, and the TM portion interacts with the lipid droplets, thereby promoting lipid droplet degradation by increasing autophagosome recognition of the lipid droplets and bringing the lipid droplets closer to the autophagosomes.

[0129] In another implementation, the TM portion itself has no affinity activity for autophagosomes or lysosomes within the cell.

[0130] LCM section

[0131] In one embodiment, the LC3-binding moiety refers to the portion that has an affinity for the LC3 protein. In one embodiment, the LCM moiety is a structure of formula (1) or a pharmaceutically acceptable salt thereof:

[0132]

[0133] in:

[0134] Ring A is a benzene ring;

[0135] The B ring is a saturated or unsaturated five- or six-membered heterocycle, which contains one, two or three heteroatoms each independently selected from N, O and S;

[0136] Ring C is selected from C 6-10 Aryl and five- to ten-membered heteroaryl groups, wherein the aryl or heteroaryl group is optionally selected from one or more independently selected from R X1 Substitution of groups;

[0137] L 1 It is a bond, or a C1-C6 hydrocarbon chain;

[0138] Alternatively, the C-ring does not exist, and L 1 It does not exist;

[0139] R 1 =Y, where Y is O or S, or OR 7 ;

[0140] R2 Each occurrence is independently selected from H, halogen, -NO2, -CN, and C. 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 3-10 Cyclic hydrocarbon group, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl, ternary to ten-membered heterocyclic groups, ternary to ten-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl-C 1-4 Alkyl, =O, =S, =NR a1 -OR a1 -SR a1 -NR a1 R b1 -C(=O)OR a1 -C(=O)NR a1 R b1 -C(=O)R a1 -S(=O)2OR a1 -S(=O)2R a1 -S(=O)2NR a1 R b1 -S(=O)R a1 -C(=S)OR a1 -C(=S)NR a1 R b1 -C(=S)R a1 -P(=O)(OR) a1 OR b1 -C(=NR) a1 )NR b1 R c1 -OCN, -SCN, -N=C=O, -NCS, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more halogens, -NO2, -CN, C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 Alkyne group, =O, =S, -OR a2 -SR a2 -NR a2 R b2 -C(=O)OR a2 -C(=O)NR a2 R b2 -C(=O)R a2 -S(=O)2OR a2 -S(=O)2R a2-S(=O)2NR a2 R b2 -S(=O)R a2 and -C(=NR) a2 )NR b2 R c2 Substituents of the substituents;

[0141] R 3 R 4 R 5 R 6 Each is independently selected from H and R X2 ;

[0142] R X1 and R X2 Each time it appears, it is independently selected from halogen, -NO2, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -OR 7 -SR 7 -NR 7 R 8 -C(=O)OR 7 -C(=O)NR 7 R 8 -OC(=O)R 7 -NC(=O)R 7 R 8 -C(=O)R 7 -S(=O)2OR 7 -S(=O)2R 7 -S(=O)2NR 7 R 8 -OS(=O)2R 7 -NS(=O)2R 7 R 8 -S(=O)R 7 The alkyl, alkenyl, or alkynyl group is optionally selected from one or more halogens, -NO2, -CN, -OH, -O(C 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 alkylene (tri- to seven-membered heterocyclic groups) 2, =O, -COOH and C 1-6 Alkyl substituents;

[0143] R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl-C 1-4 Alkyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic or aryl group is optionally composed of one or more elements selected from halogen, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Substitution of alkyl groups;

[0144] R a1 R b1 R c1 R a2 R b2 R c2Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl, five- to ten-membered heteroaryl-C 1-4 Alkyl, -OR Y1 -SR Y1 -NR Y1 R Y2 -C(=O)OR Y1 -C(=O)NR Y1 R Y2 -C(=O)R Y1 -S(=O)2OR Y1 -S(=O)2R Y1 -S(=O)2NR Y1 R Y2 -S(=O)R Y1 The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more halogens, =O, =S, -OR. Y3 -SR Y3 -NR Y3 R Y4 -C(=O)R Y3 -C(=O)OR Y3 and -C(=O)NR Y3 R Y4 Substituents of the substituents;

[0145] R Y1 R Y2 R Y3 R Y4 Each time it appears, it is independently selected from H and C. 1-8 Alkyl, C 3-10 Cyclic hydrocarbon group, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl, ternary to ten-membered heterocyclic groups, ternary to ten-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl, five- to ten-membered heteroaryl-C 1-4Alkyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more halogens, -NO2, -CN, C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 Substitution of alkynyl, -OH, -SH, -NH2, =O and -COOH groups;

[0146] n is 1 or 2.

[0147] In one implementation scheme, R 1 =O. In another implementation, R 1 =S. In another implementation, R 1 OR 7 .

[0148] In one embodiment, the B ring is a saturated or unsaturated five- or six-membered heterocycle containing one, two, or three heteroatoms each independently selected from N, O, and S. In another embodiment, the B ring is a saturated or unsaturated five-membered heterocycle containing one or two heteroatoms each independently selected from N and O. In another embodiment, the B ring is dihydropyrrole. In yet another embodiment, the B ring is selected from 2,3-dihydro-1H-pyrrole and 3,4-dihydro-1H-pyrrole, preferably 2,3-dihydro-1H-pyrrole. In still another embodiment, the B ring is pyrrolidine.

[0149] In a more preferred embodiment, the AB ring system is Where Y is O or S; and the C ring is a five- to seven-membered heteroaryl, preferably a five- to six-membered heteroaryl, particularly a five-membered heteroaryl, wherein the heteroaryl is optionally composed of 1, 2, 3, 4 or 5 independently selected from R. X1 The group is substituted. In a particular embodiment, the AB ring system is... Furthermore, the C ring is a five- to seven-membered heteroaryl group, preferably a five- to six-membered heteroaryl group, particularly a five-membered heteroaryl group, wherein the heteroaryl group is optionally composed of 1, 2, 3, 4, or 5 independently selected from R. X1 The C ring is substituted with a group. In another embodiment, the C ring contains 1, 2, 3, or 4 heteroatoms, each heteroatom independently selected from N, O, and S, preferably N and O. In yet another embodiment, the C ring contains at least one N atom. In one embodiment, the C ring is a five-membered heteroaryl group containing 1 or 2 N atoms, optionally substituted with 1, 2, 3, 4, or 5 heteroatoms independently selected from R. X1 The group is substituted. In another embodiment, the C ring is selected from pyrrole and imidazole.

[0150] In one embodiment, the B ring is a saturated or unsaturated six-membered heterocycle containing one or two heteroatoms, each independently selected from N and O. In another embodiment, the B ring is a dihydropyrimidine. In a preferred embodiment, the B ring is selected from 1,6-dihydropyrimidine, 1,2-dihydropyrimidine, and 1,4-dihydropyrimidine.

[0151] In a more preferred embodiment, the AB ring system is Where Y is O or S. In a particular embodiment, the AB ring system is...

[0152] In yet another embodiment, the B ring is 2H-pyran or 4H-pyran. In a preferred embodiment, the AB ring system is... Where Y is O or S. In a particular embodiment, the AB ring system is...

[0153] In yet another embodiment, ring C is a phenyl group, optionally surrounded by 1, 2, 3, 4, or 5 groups, each independently selected from R. X1 Substitution of groups.

[0154] In one implementation scheme, L 1 As a key. In another embodiment, L 1 It is a C1-C6 hydrocarbon chain. In a preferred embodiment, L 1 It is a C1-C2 hydrocarbon chain.

[0155] In one implementation scheme, the AB ring system is The C-ring does not exist, and L 1 It does not exist.

[0156] In another implementation:

[0157] Ring A is a benzene ring;

[0158] The B ring is a saturated or unsaturated five- or six-membered heterocycle, which contains one, two or three heteroatoms each independently selected from N, O and S;

[0159] Ring C is selected from C 6-10 Aryl and five- to ten-membered heteroaryl groups, wherein the aryl or heteroaryl group is optionally selected from one or more independently selected from R X1 Substitution of groups;

[0160] L 1 It is a bond, or a C1-C6 hydrocarbon chain;

[0161] R 1 =Y, where Y is O or S, or OR 7 ;

[0162] R 2Each occurrence is independently selected from H, halogen, -NO2, -CN, and C. 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 3-10 Cyclic hydrocarbon group, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl, ternary to ten-membered heterocyclic groups, ternary to ten-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl-C 1-4 Alkyl, =O, =S, =NR a1 -OR a1 -SR a1 -NR a1 R b1 -C(=O)OR a1 -C(=O)NR a1 R b1 -C(=O)R a1 -S(=O)2OR a1 -S(=O)2R a1 -S(=O)2NR a1 R b1 -S(=O)R a1 -C(=S)OR a1 -C(=S)NR a1 R b1 -C(=S)R a1 -P(=O)(OR) a1 OR b1 -C(=NR) a1 )NR b1 R c1 -OCN, -SCN, -N=C=O, -NCS, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more halogens, -NO2, -CN, C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 Alkyne group, =O, =S, -OR a2 -SR a2 -NR a2 R b2 -C(=O)OR a2 -C(=O)NR a2 R b2 -C(=O)R a2 -S(=O)2OR a2 -S(=O)2R a2 -S(=O)2NRa2 R b2 -S(=O)R a2 and -C(=NR) a2 )NR b2 R c2 Substituents of the substituents;

[0163] R 3 R 4 R 5 R 6 Each is independently selected from H and R X2 ;

[0164] R X1 and R X2 Each time it appears, it is independently selected from halogen, -NO2, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -OR 7 -SR 7 -NR 7 R 8 -C(=O)OR 7 -C(=O)NR 7 R 8 -OC(=O)R 7 -NC(=O)R 7 R 8 -C(=O)R 7 -S(=O)2OR 7 -S(=O)2R 7 -S(=O)2NR 7 R 8 -OS(=O)2R 7 -NS(=O)2R 7 R 8 -S(=O)R 7 The alkyl, alkenyl, or alkynyl group is optionally selected from one or more halogens, -NO2, -CN, -OH, -O(C 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4alkylene groups (-(tri- to seven-membered heterocyclic groups), -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 alkylene (tri- to seven-membered heterocyclic groups) 2, =O, -COOH and C 1-6 Alkyl substituents;

[0165] R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl-C 1-4 Alkyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic or aryl group is optionally selected from one or more halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Substitution of alkyl groups;

[0166] R a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C.1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl, five- to ten-membered heteroaryl-C 1-4 Alkyl, -OR Y1 -SR Y1 -NR Y1 R Y2 -C(=O)OR Y1 -C(=O)NR Y1 R Y2 -C(=O)R Y1 -S(=O)2OR Y1 -S(=O)2R Y1 -S(=O)2NR Y1 R Y2 -S(=O)R Y1 The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more halogens, =O, =S, -OR. Y3 -SR Y3 -NR Y3 R Y4 -C(=O)R Y3 -C(=O)OR Y3 and -C(=O)NR Y3 R Y4 Substituents of the substituents;

[0167] R Y1 R Y2 R Y3 R Y4 Each time it appears, it is independently selected from H and C. 1-8 Alkyl, C 3-10 Cyclic hydrocarbon group, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl, ternary to ten-membered heterocyclic groups, ternary to ten-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl, five- to ten-membered heteroaryl-C 1-4Alkyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more halogens, -NO2, -CN, C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 Substitution of alkynyl, -OH, -SH, -NH2, =O and -COOH groups;

[0168] n is 1.

[0169] Therefore, in one embodiment, formula (I) has the structure of formula (i), wherein the LCM portion is the structure of formula (1) above (see formula (1) and its embodiments above) or a pharmaceutically acceptable salt thereof.

[0170]

[0171] In one implementation, L can be covalently linked to any suitable site of formula (1).

[0172] The structure described in equation (2) falls within the scope of the structure described in equation (1). In one embodiment, the LCM portion has the structure described in equation (2):

[0173]

[0174] in:

[0175] Y is either O or S;

[0176] Ring C is selected from C 6-10 Aryl and five- to seven-membered heteroaryl groups, wherein the aryl or heteroaryl group is optionally selected from one or more independently selected from R X1 Substitution of groups;

[0177] R 2 Selected from H, C 1-8 alkyl;

[0178] L 1 It is a bond, or a C1-C6 hydrocarbon chain;

[0179] R 3 R 4 R 5 R 6 Each is independently selected from H and R X2 ;

[0180] Where R X1 R X2 As defined in equation (1).

[0181] In one implementation, Y is 0. When Y is 0, equation (2) is:

[0182] In one embodiment, the C ring is a five- to six-membered heteroaryl group, wherein the heteroaryl group is optionally composed of 1, 2, 3, 4, or 5 members, each independently selected from R. X1 The C ring is substituted with a group. In a preferred embodiment, the C ring is a five-membered heteroaryl group, wherein the heteroaryl group is optionally replaced by 1, 2, 3, 4 or 5 groups, each independently selected from R. X1 The C ring is substituted with a group. In another embodiment, the C ring contains 1, 2, 3, or 4 heteroatoms, each heteroatom independently selected from N, O, and S, preferably N and O. In yet another embodiment, the C ring contains at least one N atom. In one embodiment, the C ring is a five-membered heteroaryl group containing 1 or 2 N atoms, optionally substituted with 1, 2, 3, 4, or 5 heteroatoms independently selected from R. X1 The group is substituted. In another embodiment, the C ring is selected from pyrrole and imidazole.

[0183] In one implementation scheme, L 1 As a key. In another embodiment, L 1 It is a C1-C6 hydrocarbon chain. In a preferred embodiment, L 1 It is a C1-C2 hydrocarbon chain. In one embodiment, L 1 It is methylene or methine. In a particular embodiment, L 1 It is methine. In another particular embodiment, L 1 for

[0184] In another particular embodiment, the structure of formula (2) is selected from compounds A1, A2, and A3:

[0185]

[0186] Therefore, in one embodiment, formula (I) has the structure of formula (ii) below, wherein the LCM portion is the structure of formula (2) above (see formula (2) and its embodiments above) or a pharmaceutically acceptable salt thereof.

[0187]

[0188] In one embodiment, L can be covalently linked to any suitable site of formula (2). Suitable sites include, for example, -OH, a suitable heterocyclic N atom, etc.

[0189] In another particular embodiment, the structure of formula (2) is selected from compounds A1, A2, and A3:

[0190]

[0191] The structure described in equation (3) falls within the scope of the structure described in equation (1). In one embodiment, the LCM portion has the structure described in equation (3):

[0192]

[0193] in:

[0194] The B ring is a saturated or unsaturated six-membered heterocycle containing one, two, or three heteroatoms each independently selected from N, O, and S;

[0195] C ring is C 6-10 aryl groups, optionally composed of one or more independently selected from R X1 Substitution of groups;

[0196] Alternatively, the C-ring does not exist, and L 1 It does not exist;

[0197] Ring A, L 1 R 1 R 2 R 3 R 4 R 5 R 6 R X1 , n is as defined in equation (1).

[0198] In one embodiment, the B ring is a saturated or unsaturated six-membered heterocycle containing one, two, or three heteroatoms each independently selected from N, O, and S. In another embodiment, the B ring is a dihydropyrimidine. In a preferred embodiment, the B ring is selected from 1,6-dihydropyrimidine, 1,2-dihydropyrimidine, and 1,4-dihydropyrimidine.

[0199] In a more preferred embodiment, the AB ring system is Where Y is O or S. In a particular embodiment, the AB ring system is...

[0200] In yet another embodiment, the B ring is 2H-pyran or 4H-pyran. In a preferred embodiment, the AB ring system is... Where Y is O or S. In a particular embodiment, the AB ring system is...

[0201] In yet another embodiment, ring C is a phenyl group, optionally surrounded by 1, 2, 3, 4, or 5 groups, each independently selected from R. X1 Substitution of groups.

[0202] In one implementation scheme, L1 As a key. In another embodiment, L 1 It is a C1-C6 hydrocarbon chain. In a preferred embodiment, L 1 It is a C1-C2 hydrocarbon chain.

[0203] In one implementation scheme, the AB ring system is The C-ring does not exist, and L 1 It does not exist.

[0204] Therefore, in one embodiment, formula (I) has the structure of formula (iii) below, wherein the LCM portion is the structure of formula (3) above (see formula (3) and its embodiments above) or a pharmaceutically acceptable salt thereof.

[0205]

[0206] In one implementation, L can be covalently linked to any suitable site of equation (3).

[0207] In an alternative embodiment, the B and C rings of the compound of formula (3) are further permeated by L... 2 By linking them together, a variant of the compound of formula (3) is obtained, which has the structure of formula (3').

[0208]

[0209] in:

[0210] C ring is C 6-10 aryl groups, optionally composed of one or more independently selected from R X1 Substitution of groups;

[0211] R 1 For H, =O, or OR 7 ;

[0212] L 1 It is a bond, or a C1-C2 hydrocarbon chain;

[0213] L 2 It is a bond, or a C1-C2 hydrocarbon chain;

[0214] The premise is L 1 and L 2 Not both are keys;

[0215] R 3 R 4 R 5 R 6 Each is independently selected from H and R X2 ;

[0216] Ring A, Ring B, R 2 n, RX1 As defined in equation (3).

[0217] In one implementation scheme, R 1 For H.

[0218] In another implementation, R 2 It is -OH.

[0219] In one implementation scheme, R X2 Each time it appears, it is independently selected from halogen, -NO2, -CN, C. 1-6 Alkyl, -OH, -O(C) 1-6 alkyl).

[0220] Therefore, in one embodiment, formula (I) has the structure of formula (iii') as follows, wherein the LCM portion is the structure of formula (3') above (see formula (3') and its embodiments above) or a pharmaceutically acceptable salt thereof.

[0221]

[0222] In one implementation, L can be covalently linked to any suitable site of formula (3').

[0223] The structure described in equation (4) falls within the scope of the structures described in equations (1) and (3). In one embodiment, the LCM portion has the structure described in equation (4):

[0224]

[0225] in:

[0226] Y is either O or S;

[0227] X is O;

[0228] R 9 Selected from H, halogens, C 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OR a1 -SR a1 -NR a1 R b1 -C(=O)OR a1 -C(=O)NR a1 R b1 -C(=O)R a1 -S(=O)2OR a1 -S(=O)2R a1 -S(=O)2NRa1 R b1 -S(=O)R a1 The alkyl, cyclic, or heterocyclic group is optionally selected from one or more halogens, -NO2, -CN, C 1-6 Alkyl, -OR a2 -SR a2 -NR a2 R b2 -C(=O)OR a2 -C(=O)NR a2 R b2 -C(=O)R a2 -S(=O)2OR a2 -S(=O)2R a2 -S(=O)2NR a2 R b2 and -S(=O)R a2 Substituents of R; where R a1 R b1 R a2 R b2 As defined in equation (3);

[0229] R 10 Selected from H, halogens, C 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 alkyl;

[0230] R 3 Selected from H, halogens, C 1-6 Alkyl, -OH, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution of alkyl group 2;

[0231] R 4 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, -OR 7 -SR 7 -NR 7 R 8 ;R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Substitution of alkyl groups;

[0232] R 5 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Alkyl group), wherein the alkyl group is optionally composed of one or more elements selected from halogens, -OH, -O (C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Substitution of alkyl groups;

[0233] R 6 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl), -O (benzyl), -SH, -S (C 1-6 Alkyl), -S (benzyl), -NH2, -NH (C 1-6alkyl), -N(C) 1-6 Alkyl group 2, -NH (benzyl), wherein the alkyl or benzyl group is optionally surrounded by one or more elements selected from halogen, -OH, -O (C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2 substituents.

[0234] In one implementation, Y is 0. When Y is 0, equation (4) is:

[0235] In one implementation scheme, R 9 Selected from H, halogens, C 1-6 Alkyl, -OR a1 -NR a1 R b1 -C(=O)OR a1 -C(=O)NR a1 R b1 -S(=O)2NR a1 R b1 The alkyl group is optionally surrounded by one or more elements selected from halogens, -NO2, -CN, C. 1-6 Alkyl, -OR a2 -SR a2 -NR a2 R b2 -C(=O)OR a2 -C(=O)NR a2 R b2 -C(=O)R a2 Substituents are substituted. In one embodiment, R 9 Selected from H, halogen, -OR a1 -NR a1 R b1 -C(=O)OR a1 -C(=O)NR a1 R b1 In one implementation scheme, R 9 For -OR a1 or -NR a1 R b1 In another implementation, R 9 -C(=O)OR a2 or -C(=O)NR a2 R b2 In one particular implementation scheme, R 9 -C(=O)O(C 1-6 Alkyl group). In a particular embodiment, R 9 It is -COOH.

[0236] In one implementation scheme, R 10 Selected from H, halogen, or methyl. In another embodiment, R 10 For H.

[0237] In one implementation scheme, R a1 R b1 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, -C(=O)R Y1 The alkyl group is optionally selected from one or more halogens, -OR Y3 -SR Y3 -NR Y3 R Y4 -C(=O)R Y3 -C(=O)OR Y3 and -C(=O)NR Y3 R Y4 Substituents of R. Y1 R Y3 R Y4 As defined in equation (3). In one implementation, R a1 R b1 Each time it appears, it is independently selected from H and C. 1-6 Alkyl group, -C(=O)(C 1-6 Alkyl group), wherein the alkyl group is optionally composed of one or more elements selected from halogens, -OH, -O (C 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 Cyclic hydrocarbon group) 2, -C (=O)(C 1-6 Alkyl), -C(=O)O(C 1-6 Alkyl), -C(=O)O(C 3-6 cyclic hydrocarbon group), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 The alkyl group is substituted. In one embodiment, R... a1 R b1 Each time it appears, it is independently selected from H and C. 1-6 alkyl.

[0238] In one implementation scheme, R a2 R b2 Each time it appears, it is independently selected from H and C. 1-6 alkyl.

[0239] In one implementation scheme, R 3 Selected from H, -OH, C 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, -OH, -SH, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group) 2, -NH (three to seven-membered heterocyclic group), -N (three to seven-membered heterocyclic group) 2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 Substitution with alkylene-ternary to seven-membered heterocyclic groups (2) and -COOH. In one embodiment, R 3 The group is selected from H, halogen, methyl, -OH, -NH2, -NHCH3, wherein the methyl group is optionally selected from halogen, -OH, -NH2, -NH(C 1-2 The alkyl group is substituted. In one embodiment, R 3 The group is selected from H, halogen, methyl, -OH, -NH2, -NHCH3, wherein the methyl group is optionally substituted with a substituent selected from halogen, -OH, -OCH3, -NH2, -NHCH3. In one embodiment, R 3 Selected from H, halogens, methyl groups, -OH, and -NH2. In one embodiment, R... 3 Selected from H, F, Cl, methyl, -OH, -NH2. In another embodiment, R 3 Selected from H, F, methyl, -OH, -NH2. In a particular embodiment, R 3 Selected from H, methyl, -OH. In another particular embodiment, R 3 For H. In yet another specific implementation, R 3 For -OH. In another embodiment, R 3 It is dimethylaminomethyl.

[0240] In one implementation scheme, R 4 Selected from H, -OR 7 -SR 7 -NR 7 R 8 ;R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 The alkyl group is substituted. In one embodiment, R... 4 C 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 The alkyl group is substituted. In a particular embodiment, R... 4 For -CH2COOH. In another embodiment, R 4 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 The alkyl group is substituted. In one embodiment, R... 4 Selected from H, halogens, C 1-3 Alkyl, -OH, -O(C) 1-3 Alkyl groups, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl group 2 and -COOH, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-2 Alkyl groups, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 Substituents of alkyl groups (2) and -COOH. In another particular embodiment, R 4 It is -OH.

[0241] In one implementation scheme, R 5 Selected from H, C 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, -OH, -O(C)1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 Substituents of alkylene-tertiary to heptaneous groups (2) and -COOH. In another embodiment, R 5 Selected from H, halogens, C 1-3 Alkyl, -OH, -O(C) 1-3 Alkyl groups, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl group 2 and -COOH, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-2 Alkyl groups, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 Substituents of alkyl groups (2) and -COOH. In one embodiment, R 5 Selected from H, halogens, C 1-3 Alkyl, -OH, -O(C) 1-3 Alkyl groups, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-2 Alkyl groups, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 The alkyl group is substituted. In one embodiment, R...5 It is dimethylaminomethyl. In one embodiment, R 5 It is -OH.

[0242] In one implementation scheme, R 6 Selected from H, halogens, C 1-6 Alkyl, -OH, -NH2, wherein the alkyl group is optionally substituted with one or more substituents selected from halogens, -OH, -NH2. In one embodiment, R 6 Selected from H, F, Cl, Br, C 1-6 Alkyl, -OH, -NH2, wherein the alkyl group is optionally substituted with one or more substituents selected from halogens, -OH, -NH2. In one embodiment, R 6 Selected from H, F, Cl, Br, methyl, -OH, -NH2. In one embodiment, R 6 It can be H or -OH.

[0243] In one implementation scheme, R 3 It is methyl, and R 4 Selected from -OH, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 alkyl)2,-COOH substituted C 1-3 Alkyl, wherein the substituted C 1-3 Alkyl groups are selected from one or more groups chosen from -OH, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 Substituents of alkyl groups (2) and -COOH. In one embodiment, R 3 It is methyl, and R 4 Selected from -NH2, -NH(C 1-3 alkyl), -N(C) 1-3 alkyl)2,-COOH substituted C 1-3 Alkyl, wherein the substituted C 1-3 Alkyl groups are selected from one or more groups chosen from -OH, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 Substitution with alkyl groups (2) and -COOH.

[0244] In another implementation, R 3 It is methyl, and R 5 Selected from -OH, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 alkyl)2,-COOH substituted C 1-3 Alkyl, wherein the substituted C 1-3 Alkyl groups are selected from one or more groups chosen from -OH, -NH2, -NH(C) 1-2alkyl), -N(C) 1-2 Substituents of alkyl group (2) and -COOH. In another embodiment, R 3 It is methyl, and R 5 Selected from -NH2, -NH(C 1-3 alkyl), -N(C) 1-3 alkyl)2,-COOH substituted C 1-3 Alkyl, wherein the substituted C 1-3 Alkyl groups are selected from one or more groups chosen from -OH, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 Substitution with alkyl groups (2) and -COOH.

[0245] Therefore, in one embodiment, formula (I) has the structure of formula (iv), wherein the LCM portion is the structure of formula (4) above (see formula (4) and its embodiments) or a pharmaceutically acceptable salt thereof.

[0246]

[0247] In one implementation, L can be covalently linked to any suitable site of equation (4).

[0248] The structure described in equation (5) falls within the scope of the structures described in equations (1), (3), and (4). In one embodiment, the LCM portion has the structure described in equation (5):

[0249]

[0250] in:

[0251] Y, R 9 R 10 R 3 R 4 R 5 R 6 As defined in equation (4);

[0252] In one implementation, Y is 0. When Y is 0, equation (5) is:

[0253] In one particular embodiment, the structure of formula (5) is compound A4.

[0254] Therefore, in one embodiment, formula (I) has the structure of formula (v) below, wherein the LCM portion is the structure of formula (5) above (see formula (5) and its embodiments) or a pharmaceutically acceptable salt thereof.

[0255]

[0256] In one embodiment, L can be covalently linked to any suitable site of formula (5). Suitable sites include, for example, -OH, -COOH, etc.

[0257] In a particular implementation, the structure of equation (v) is as follows:

[0258] The structure described in equation (6) falls within the scope of the structures described in equations (1) and (3). In one embodiment, the LCM portion has the structure described in equation (6):

[0259]

[0260] in:

[0261] The B ring is a saturated or unsaturated six-membered heterocycle containing one, two, or three heteroatoms each independently selected from N, O, and S;

[0262] C ring is C 6-10 aryl groups, optionally composed of one or more independently selected from R X1 Substitution of groups;

[0263] L 1 It is a bond, or a C1-C6 hydrocarbon chain;

[0264] R 2 Selected from H, halogens, -NO2, -CN, C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 alkynyl group, C 3-10 Cyclic hydrocarbon group, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl, ternary to ten-membered heterocyclic groups, ternary to ten-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl-C 1-4 Alkyl, =O, =S, =NR a1 -OR a1 -SR a1 -NR a1 R b1 -C(=O)OR a1 -C(=O)NR a1 R b1 -C(=O)R a1 -S(=O)2OR a1 -S(=O)2R a1 -S(=O)2NR a1 R b1 -S(=O)R a1-C(=S)OR a1 -C(=S)NR a1 R b1 -C(=S)R a1 -P(=O)(OR) a1 OR b1 -C(=NR) a1 )NR b1 R c1 -OCN, -SCN, -N=C=O, -NCS, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more halogens, -NO2, -CN, C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 Alkyne group, =O, =S, -OR a2 -SR a2 -NR a2 R b2 -C(=O)OR a2 -C(=O)NR a2 R b2 -C(=O)R a2 -S(=O)2OR a2 -S(=O)2R a2 -S(=O)2NR a2 R b2 -S(=O)R a2 and -C(=NR) a2 )NR b2 R c2 Substituents of the substituents;

[0265] R 3 R 4 R 5 R 6 Each is independently selected from H and R X2 ;

[0266] R X1 and R X2 Each time it appears, it is independently selected from halogen, -NO2, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, -OR 7 -SR 7 -NR 7 R 8 -C(=O)OR 7 -C(=O)NR 7 R 8 -OC(=O)R 7 -NC(=O)R7 R 8 -C(=O)R 7 -S(=O)2OR 7 -S(=O)2R 7 -S(=O)2NR 7 R 8 -OS(=O)2R 7 -NS(=O)2R 7 R 8 -S(=O)R 7 The alkyl, alkenyl, or alkynyl group is optionally selected from one or more halogens, -NO2, -CN, -OH, -O(C 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 alkylene (tri- to seven-membered heterocyclic groups) 2, =O, -COOH and C 1-6 Alkyl substituents;

[0267] R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl or heterocyclic group is optionally selected from one or more halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Substitution of alkyl groups;

[0268] R a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl, five- to ten-membered heteroaryl-C 1-4 Alkyl, -OR Y1 -SR Y1 -NR Y1 R Y2 -C(=O)OR Y1 -C(=O)NR Y1 R Y2 -C(=O)R Y1 -S(=O)2OR Y1 -S(=O)2R Y1 -S(=O)2NR Y1 R Y2 -S(=O)R Y1 The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more halogens, =O, =S, -OR.Y3 -SR Y3 -NR Y3 R Y4 -C(=O)R Y3 -C(=O)OR Y3 and -C(=O)NR Y3 R Y4 Substituents of the substituents;

[0269] R Y1 R Y2 R Y3 R Y4 Each time it appears, it is independently selected from H and C. 1-8 Alkyl, C 3-10 Cyclic hydrocarbon group, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl, ternary to ten-membered heterocyclic groups, ternary to ten-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl, five- to ten-membered heteroaryl-C 1-4 Alkyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more halogens, -NO2, -CN, C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 Substitution of alkynyl, -OH, -SH, -NH2, =O and -COOH groups;

[0270] Ring A, R 1 As defined in equation (3).

[0271] In one embodiment, the B ring is a saturated or unsaturated six-membered heterocycle containing one or two heteroatoms, each independently selected from N and O. In another embodiment, the B ring is a dihydropyrimidine. In a preferred embodiment, the B ring is selected from 1,6-dihydropyrimidine, 1,2-dihydropyrimidine, and 1,4-dihydropyrimidine.

[0272] In a more preferred embodiment, the AB ring system is Where Y is O or S. In a particular embodiment, the AB ring system is...

[0273] In yet another embodiment, the B ring is 2H-pyran or 4H-pyran. In a preferred embodiment, the AB ring system is... Where Y is O or S. In a particular embodiment, the AB ring system is...

[0274] In yet another embodiment, ring C is a phenyl group, optionally surrounded by 1, 2, 3, 4, or 5 groups, each independently selected from R. X1 Substitution of groups.

[0275] In one implementation scheme, L 1 As a key. In another embodiment, L 1 It is a C1-C6 hydrocarbon chain. In a preferred embodiment, L 1 It is a C1-C2 hydrocarbon chain.

[0276] In yet another implementation scheme, R 2 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, =O, =S, -OR a1 -SR a1 -NR a1 R b1 -C(=O)OR a1 -C(=O)NR a1 R b1 -C(=O)R a1 -S(=O)2OR a1 -S(=O)2R a1 -S(=O)2NR a1 R b1 -S(=O)R a1 The alkyl, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally selected from one or more halogens, -NO2, -CN, C 1-6 Alkyl, -OR a2 -SR a2 -NR a2 R b2 -C(=O)OR a2 -C(=O)NR a2 R b2 -C(=O)R a2 -S(=O)2OR a2 -S(=O)2R a2 -S(=O)2NR a2 R b2 and -S(=O)R a2 Substituents are substituted. In another embodiment, R 2 Selected from H, halogens, -NO2, -CN, =O, =S, C 1-6Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 Cyclic hydrocarbon group), -O (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (-(tri- to seven-membered heterocyclic groups), -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cyclic hydrocarbon group), -NH (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -NH(C=O) (three- to seven-membered heterocyclic groups), -C(=O) (C 1-6 Alkyl groups, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)O(C3-6 cyclic hydrocarbon group), -C(=O)O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -C(=O)O (three- to seven-membered heterocyclic groups), -C(=O)O (C 1-4 Alkylene group (ternary to seven-membered heterocyclic group), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-C(=O)NH(C 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -C(=O)N(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -C(=O)NH (three- to seven-membered heterocyclic group), -C(=O)N (three- to seven-membered heterocyclic group)2, -C(=O)NH (C 1-4 alkylene-tertiary to seven-membered heterocyclic groups), -C(=O)N(C 1-4 2. Alkylene-tertiary to seven-membered heterocyclic group, wherein the alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally substituted by one or more substituents selected from halogen, nitro, cyano, -OH, -SH, -NH2, and -COOH. In yet another embodiment, R 2 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OR a1 -SR a1 -NR a1 R b1 -C(=O)OR a1 -C(=O)NR a1 R b1 -C(=O)R a1 -S(=O)2OR a1 -S(=O)2R a1 -S(=O)2NR a1 R b1 -S(=O)R a1 The alkyl, cyclic, or heterocyclic group is optionally selected from one or more halogens, -NO2, -CN, C 1-6 Alkyl, -OR a2 -SR a2 -NR a2 R b2 -C(=O)OR a2 -C(=O)NRa2 R b2 -C(=O)R a2 Substituents are substituted. In a preferred embodiment, R 2 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl group, -OH group, wherein the alkyl group is optionally surrounded by one or more elements selected from halogen, -NO2, -CN, C. 1-6 Alkyl, -NR a2 R b2 Substituents are substituted. In a more preferred embodiment, R 2 Selected from H, halogens, C 1-6 Alkyl group, -OH group, wherein the alkyl group is optionally surrounded by one or more elements selected from halogens, C 1-6 Alkyl and -NR a2 R b2 The group is substituted. In a further embodiment, R 2 Selected from H, C 1-4 Alkyl group, -OH group, wherein the alkyl group is optionally composed of one or more molecules selected from -NR. a2 R b2 The group is substituted. In a particular embodiment, R 2 Selected from H, C 1-4 Alkyl group, -OH group, wherein the alkyl group is -CH2[CH(CH3)2], and optionally is selected from one or more groups selected from -NR. a2 R b2 The group is substituted. In another embodiment, R... 2 For -NR a1 R b1 Substituted alkyl groups. In a particular embodiment, R 2 for

[0277] In one implementation scheme, R X1 and R X2 Each time it appears, it is independently selected from halogen, -NO2, -CN, C. 1-6 Alkyl, -OR 7 -SR 7 -NR 7 R 8 -C(=O)OR 7 -C(=O)NR 7 R 8 -OC(=O)R 7 -NC(=O)R 7 R 8 -C(=O)R 7 -S(=O)2OR 7 -S(=O)2R 7-S(=O)2NR 7 R 8 -OS(=O)2R 7 -NS(=O)2R 7 R 8 -S(=O)R 7 The alkyl group is optionally surrounded by one or more elements selected from halogens, -NO2, -CN, -OH, -O(C). 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 Substitution with alkylene-tertiary to seven-membered heterocyclic groups (2), =O, -COOH. In a preferred embodiment, R X1 and R X2 Each time it appears, it is independently selected from halogen, -NO2, -CN, C. 1-6 Alkyl, -OR 7 -SR 7 -NR 7 R 8 -OC(=O)R 7 -NC(=O)R 7 R 8 -OS(=O)2R 7 -NS(=O)2R 7 R 8 The alkyl group is optionally surrounded by one or more elements selected from halogens, -NO2, -CN, -OH, -O(C).1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 Substituents of alkylene-tertiary to seven-membered heterocyclic groups (2). In a preferred embodiment, R X1 and R X2 Each time it appears, it is independently selected from halogens and C. 1-6 Alkyl, -OR 7 -NR 7 R 8 More preferably, each is independently selected from halogens, -OR 7 The alkyl group is optionally surrounded by one or more elements selected from halogens, -NO2, -CN, -OH, -O(C). 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 The alkyl group is substituted with a substituent. In a more preferred embodiment, R X1 and R X2 Each time it appears, it is independently selected from F, Cl, Br, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl)2, optionally substituted C 1-6 Alkyl groups, wherein the optionally substituted C 1-6 Alkyl groups are optionally surrounded by one or more elements selected from halogens, -NO2, -CN, -OH, and -O(C). 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 The alkyl group is substituted. In a particular embodiment, R... X1 and R X2Each of these elements is independently selected from F, Cl, Br, methyl, -OH, and dimethylaminomethyl each time it appears.

[0278] R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, wherein the alkyl, alkenyl, or alkynyl group is optionally selected from one or more halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 The alkyl group is substituted. In a preferred embodiment, R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Alkyl groups are substituted. In a particular embodiment, R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, -N(C) 1-6 Alkyl group 2, -COOH substituent. In another particular embodiment, R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, -N(C) 1-6 Alkyl)2 substituents.

[0279] In one implementation scheme, R a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl-C 1-4 Alkyl, -OR Y1 -SR Y1 -NR Y1 R Y2 -C(=O)OR Y1 -C(=O)NR Y1 R Y2 -C(=O)R Y1 The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are optionally selected from one or more halogens, -OR Y3 -SR Y3 -NR Y3 R Y4 -C(=O)R Y3 -C(=O)OR Y3 and -C(=O)NR Y3 R Y4 Substituents are substituted. In a preferred embodiment, R a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl-C 1-4 Alkyl, -OR Y1 -SR Y1 -NR Y1 R Y2 -C(=O)OR Y1 -C(=O)NR Y1 RY2 -C(=O)R Y1 The alkyl, aryl, or heteroaryl group is optionally selected from one or more halogens, -OR Y3 and -NR Y3 R Y4 The substituent is replaced. In another preferred embodiment, R a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, -OR Y1 -NR Y1 R Y2 -C(=O)OR Y1 -C(=O)NR Y1 R Y2 -C(=O)R Y1 The alkyl group is optionally selected from one or more halogens, -OR Y3 and -NR Y3 R Y4 The group is substituted. In a more preferred embodiment, R... a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, -OR Y1 -NR Y1 R Y2 -C(=O)R Y1 The alkyl group is optionally selected from one or more halogens, -OR Y3 and -NR Y3 R Y4 The group is substituted. In a further embodiment, R a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, -OR Y1 -NR Y1 R Y2 -C(=O)R Y1 The alkyl group is optionally selected from one or more halogens, -NR Y3 R Y4 The group is substituted. In a particular embodiment, Ra1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C. 1-3 Alkyl, -OH, p-methylbenzoyl; wherein the alkyl group is optionally substituted with one or more groups selected from halogens, -NH2.

[0280] In another implementation, R Y1 R Y2 R Y3 R Y4 Each time it appears, it is independently selected from H and C. 1-8 Alkyl, C 3-10 Cyclic hydrocarbon group, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl, ternary to ten-membered heterocyclic groups, ternary to ten-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl, five- to ten-membered heteroaryl-C 1-4 Alkyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, -OH, -SH, -NH2, -COOH, and C. 1-6 Alkyl substituents. In a preferred embodiment, R Y1 R Y2 R Y3 R Y4 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, phenyl, phenyl-C 1-4 Alkyl, five- to six-membered heteroaryl, five- to six-membered heteroaryl-C 1-4 Alkyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, -OH, -SH, -NH2, -COOH, and C. 1-6 Alkyl substituents. In a more preferred embodiment, R Y1 R Y2 R Y3 R Y4 Each time it appears, it is independently selected from H and C. 1-6Alkyl, phenyl, phenyl-C 1-4 Alkyl, five- to six-membered heteroaryl, five- to six-membered heteroaryl-C 1-4 Alkyl groups, wherein the alkyl or phenyl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, -OH, -SH, -NH2, -COOH, and C. 1-6 Alkyl substituents. In a more preferred embodiment, R Y1 R Y2 R Y3 R Y4 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, phenyl, phenyl-C 1-4 Alkyl groups, wherein the alkyl or phenyl group is optionally selected from one or more halogens, C 1-6 Alkyl groups are substituted. In a particular embodiment, R Y1 R Y2 R Y3 R Y4 Each time it appears, it is independently selected from H and p-methylphenyl.

[0281] In another implementation, R 2 Selected from H, halogens, -NO2, -CN, =O, =S, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 Cyclic hydrocarbon group), -O (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cyclic hydrocarbon group), -NH (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -NH(C=O) (three- to seven-membered heterocyclic groups), -C(=O) (C 1-6 Alkyl), -C(=O)O(C 1-6 Alkyl), -C(=O)O(C 3-6 cyclic hydrocarbon group), -C(=O)O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -C(=O)O (three- to seven-membered heterocyclic groups), -C(=O)O (C 1-4 alkylene)-(ternary to seven-membered heterocyclic groups), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-C(=O)NH(C 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -C(=O)N(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -C(=O)NH (three- to seven-membered heterocyclic group), -C(=O)N (three- to seven-membered heterocyclic group)2, -C(=O)NH (C 1-4 alkylene-tertiary to seven-membered heterocyclic groups), -C(=O)N(C 1-4 2. Alkylene-tertiary to seven-membered heterocyclic group, wherein the alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally substituted by one or more substituents selected from halogen, nitro, cyano, -OH, -SH, -NH2. In yet another embodiment, R 2 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OR a1 -SR a1 -NR a1 R b1 -C(=O)OR a1 -C(=O)NR a1 R b1 -C(=O)R a1 -S(=O)2OR a1 -S(=O)2R a1 -S(=O)2NR a1 R b1 -S(=O)R a1 The alkyl, cyclic, or heterocyclic group is optionally selected from one or more halogens, -NO2, -CN, C 1-6 Alkyl, -OR a2 -SR a2 -NR a2 R b2 -C(=O)OR a2 -C(=O)NR a2 R b2 -C(=O)R a2 Substituents are substituted. In a preferred embodiment, R 2 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl group, -OH group, wherein the alkyl group is optionally surrounded by one or more elements selected from halogen, -NO2, -CN, C. 1-6 Alkyl, -NR a2 R b2 Substituents are substituted. In a more preferred embodiment, R 2 Selected from H, halogens, C 1-6 Alkyl group, -OH group, wherein the alkyl group is optionally surrounded by one or more elements selected from halogens, C 1-6 Alkyl and -NR a2 R b2 The group is substituted. In a further embodiment, R 2 Selected from H, C 1-4 Alkyl group, -OH group, wherein the alkyl group is optionally composed of one or more molecules selected from -NR. a2 R b2 The group is substituted. In a particular embodiment, R 2 Selected from H, C 1-4 Alkyl group, -OH group, wherein the alkyl group is -CH2[CH(CH3)2], and optionally is selected from one or more groups selected from -NR. a2 Rb2 The group is substituted. In another embodiment, R... 2 For -NR a1 R b1 Substituted alkyl groups. In a particular embodiment, R 2 for

[0282] In one implementation scheme, R X1 and R X2 Each time it appears, it is independently selected from halogen, -NO2, -CN, C. 1-6 Alkyl, -OR 7 -SR 7 -NR 7 R 8 -C(=O)OR 7 -C(=O)NR 7 R 8 -OC(=O)R 7 -NC(=O)R 7 R 8 -C(=O)R 7 -S(=O)2OR 7 -S(=O)2R 7 -S(=O)2NR 7 R 8 -OS(=O)2R 7 -NS(=O)2R 7 R 8 -S(=O)R 7 The alkyl group is optionally surrounded by one or more elements selected from halogens, -NO2, -CN, -OH, -O(C). 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (-(tri- to seven-membered heterocyclic groups), -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 Substituents of alkylene-tertiary to seven-membered heterocyclic groups (2, =O). In a preferred embodiment, R X1 and R X2 Each time it appears, it is independently selected from halogen, -NO2, -CN, C. 1-6 Alkyl, -OR 7 -SR 7 -NR 7 R 8 -OC(=O)R 7 -NC(=O)R 7 R 8 -OS(=O)2R 7 -NS(=O)2R 7 R 8 The alkyl group is optionally surrounded by one or more elements selected from halogens, -NO2, -CN, -OH, -O(C). 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 Substituents of alkylene-tertiary to seven-membered heterocyclic groups (2). In a preferred embodiment, R X1 and R X2 Each time it appears, it is independently selected from halogens and C. 1-6 Alkyl, -OR 7 -NR 7 R 8 More preferably, each is independently selected from halogens, -OR7 The alkyl group is optionally surrounded by one or more elements selected from halogens, -NO2, -CN, -OH, -O(C). 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 The alkyl group is substituted with a substituent. In a more preferred embodiment, R X1 and R X2 Each time it appears, it is independently selected from F, Cl, Br, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl)2, optionally substituted C 1-6 Alkyl groups, wherein the optionally substituted C 1-6 Alkyl groups are optionally surrounded by one or more elements selected from halogens, -NO2, -CN, -OH, and -O(C). 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 The alkyl group is substituted. In a particular embodiment, R... X1 and R X2 Each of these elements is independently selected from F, Cl, Br, methyl, -OH, and dimethylaminomethyl each time it appears.

[0283] R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, wherein the alkyl, alkenyl, or alkynyl group is optionally selected from one or more halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 The alkyl group is substituted. In a preferred embodiment, R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, C 1-6Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Alkyl groups are substituted. In a particular embodiment, R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, -N(C) 1-6 The alkyl group is substituted. In another particular embodiment, R... 7 R 8 Each time it appears, it is independently selected from H and C. 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, -N(C) 1-6 Alkyl)2 substituents.

[0284] In one implementation scheme, R a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, ternary to 7-membered heterocyclic groups, ternary to 7-membered heterocyclic groups - C 1-4 Alkyl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl-C 1-4 Alkyl, -OR Y1 -SR Y1 -NR Y1 R Y2 -C(=O)OR Y1 -C(=O)NR Y1 R Y2 -C(=O)R Y1 The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are optionally selected from one or more halogens, -OR Y3 -SRY3 -NR Y3 R Y4 -C(=O)R Y3 -C(=O)OR Y3 and -C(=O)NR Y3 R Y4 Substituents are substituted. In a preferred embodiment, R a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl-C 1-4 Alkyl, -OR Y1 -SR Y1 -NR Y1 R Y2 -C(=O)OR Y1 -C(=O)NR Y1 R Y2 -C(=O)R Y1 The alkyl, aryl, or heteroaryl group is optionally selected from one or more halogens, -OR Y3 and -NR Y3 R Y4 The substituent is replaced. In another preferred embodiment, R a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, -OR Y1 -NR Y1 R Y2 -C(=O)OR Y1 -C(=O)NR Y1 R Y2 -C(=O)R Y1 The alkyl group is optionally selected from one or more halogens, -OR Y3 and -NR Y3 R Y4 The group is substituted. In a more preferred embodiment, R... a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C.1-6 Alkyl, -OR Y1 -NR Y1 R Y2 -C(=O)R Y1 The alkyl group is optionally selected from one or more halogens, -OR Y3 and -NR Y3 R Y4 The group is substituted. In a further embodiment, R a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, -OR Y1 -NR Y1 R Y2 -C(=O)R Y1 The alkyl group is optionally selected from one or more halogens, -NR Y3 R Y4 The group is substituted. In a particular embodiment, R a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C. 1-3 Alkyl, -OH, p-methylbenzoyl; wherein the alkyl group is optionally substituted with one or more groups selected from halogens, -NH2.

[0285] In another implementation, R Y1 R Y2 R Y3 R Y4 Each time it appears, it is independently selected from H and C. 1-8 Alkyl, C 3-10 Cyclic hydrocarbon group, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl, ternary to ten-membered heterocyclic groups, ternary to ten-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl, five- to ten-membered heteroaryl-C 1-4 Alkyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more halogens, -NO2, -CN, -OH, -SH, -NH2, and C. 1-6 Alkyl substituents. In a preferred embodiment, R Y1 RY2 R Y3 R Y4 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, phenyl, phenyl-C 1-4 Alkyl, five- to six-membered heteroaryl, five- to six-membered heteroaryl-C 1-4 Alkyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more halogens, -NO2, -CN, -OH, -SH, -NH2, and C. 1-6 Alkyl substituents. In a more preferred embodiment, R Y1 R Y2 R Y3 R Y4 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, phenyl, phenyl-C 1-4 Alkyl, five- to six-membered heteroaryl, five- to six-membered heteroaryl-C 1-4 Alkyl groups, wherein the alkyl or phenyl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, -OH, -SH, -NH2, and C. 1-6 Alkyl substituents. In a more preferred embodiment, R Y1 R Y2 R Y3 R Y4 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, phenyl, phenyl-C 1-4 Alkyl groups, wherein the alkyl or phenyl group is optionally selected from one or more halogens, C 1-6 Alkyl groups are substituted. In a particular embodiment, R Y1 R Y2 R Y3 R Y4 Each time it appears, it is independently selected from H and p-methylphenyl.

[0286] In one implementation scheme, R 3 R 6 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl group), wherein the alkyl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, -OH, -O(C). 1-6 alkyl), -O(C) 3-6cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 Substitution with alkylene (-(ternary to seven-membered heterocyclic) groups). In a preferred embodiment, R 3 R 6 Each is independently selected from H, halogen, -OH, and more preferably H or -OH.

[0287] In one implementation scheme, R 4 R 5 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -NO2, -CN, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -NH(C 1-4 Alkylene-C 3-6 -cyclic hydrocarbon group), -NH (three- to seven-membered heterocyclic group), -NH (C 1-4 alkylene-tertiary to seven-membered heterocyclic groups), -COOH, -C(=O)O(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Alkyl groups and =O substituents are used. In another embodiment, R... 4 R 5 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -NO2, -CN, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)O(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Alkyl groups and =O substituents are used. In another embodiment, R... 4 R 5 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl group), wherein the alkyl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, -OH, -O(C). 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(=O)O(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Alkyl groups and =O substituents are used. In another embodiment, R... 4 R 5 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -NO2, -CN, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(=O)O(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Alkyl groups and =O substituents.

[0288] Therefore, in one embodiment, formula (I) has the structure of formula (vi), wherein the LCM portion is the structure of formula (6) above (see formula (6) and its embodiments above) or a pharmaceutically acceptable salt thereof.

[0289]

[0290] In one implementation, L can be covalently linked to any suitable site of equation (6).

[0291] The structure described in equation (7) falls within the scope of the structures described in equations (1), (3), and (6). In one embodiment, the LCM portion has the structure described in equation (7):

[0292]

[0293] in:

[0294] X is O;

[0295] Y is either O or S;

[0296] R 3 R 4 R 5 R 6 As defined in equation (6);

[0297] C ring is Where R 14 R 15 R 16 R 17 R 18 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, -OR 7 -SR 7 -NR 7 R 8 -C(=O)OR 7 -C(=O)NR 7 R 8 -OC(=O)R 7 -NC(=O)R 7 R 8 -C(=O)R 7 -S(=O)2OR 7-S(=O)2R 7 -S(=O)2NR 7 R 8 -OS(=O)2R 7 -NS(=O)2R 7 R 8 -S(=O)R 7 ;where R 7 R 8 As defined in equation (6);

[0298] R 2 Selected from H, halogens, C 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl group, wherein the alkyl group, cycloalkyl group, or heterocyclic group is optionally composed of one or more elements selected from halogen, -NO2, -CN, C 1-6 Alkyl, -OR a2 -SR a2 -NR a2 R b2 -C(=O)OR a2 -C(=O)NR a2 R b2 -C(=O)R a2 -S(=O)2OR a2 -S(=O)2R a2 -S(=O)2NR a2 R b2 and -S(=O)R a2 Substituents of R; where R a2 R b2 As defined in equation (6).

[0299] In one implementation, Y is 0. When Y is 0, equation (7) is:

[0300] In one implementation scheme, R 2 Selected from H, halogens, C 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, C. 1-6 Alkyl, -OR a2 -SR a2 -NR a2 R b2 -C(=O)OR a2 -C(=O)NR a2 R b2 -C(=O)Ra2 -S(=O)2OR a2 -S(=O)2R a2 -S(=O)2NR a2 R b2 and -S(=O)R a2 Substituents are substituted. In one embodiment, R 2 Selected from -OR a1 -NR a1 R b1 -C(=O)OR a1 -C(=O)NR a1 R b1 In another implementation, R 2 Selected from H, halogens, C 1-6 Alkyl group, wherein the alkyl group is optionally substituted with one or more substituents selected from halogen, -NO2, -CN, -OH, -NH2 and -COOH.

[0301] In one implementation scheme, R a2 R b2 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl or heterocyclic group is optionally selected from one or more halogens, -OH, -O(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 The alkyl group is substituted. In a preferred embodiment, R a2 R b2 Each time it appears, it is independently selected from H and C. 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, -OH, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl group substitution.

[0302] In one implementation scheme, R 3 Selected from H, halogens, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 The alkyl group is substituted. In one embodiment, R... 3 Selected from H, halogens, C 1-3 Alkyl, -OH, -O(C) 1-3 Alkyl groups, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-2 Alkyl groups, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 The alkyl group is substituted. In one embodiment, R... 3 The methyl group is selected from H, halogen, methyl, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, wherein the methyl group is optionally selected from halogen, -OH, -O(C 1-2 Alkyl groups, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 The alkyl group is substituted. In one embodiment, R... 3 The group is selected from H, halogen, methyl, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, wherein the methyl group is optionally substituted with a substituent selected from halogen, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2. In one embodiment, R 3 Selected from H, halogens, methyl groups, -OH, -NH2, and -N(CH3)2. In yet another embodiment, R 3 Selected from H, halogens, C 1-4 Alkyl, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 Alkyl group), wherein the alkyl group is optionally composed of one or more elements selected from halogens, -OH, -O (C 1-4 Alkyl groups, -NH2, -NH(C) 1-4 The alkyl group is substituted. In one embodiment, R 3Selected from H, halogen, methyl, -OH, -OCH3, -NH2, -NHCH3, wherein the methyl group is optionally selected from halogen, -OH, -O(C 1-2 Alkyl groups, -NH2, -NH(C) 1-2 The alkyl group is substituted. In one embodiment, R 3 The group is selected from H, halogen, methyl, -OH, -OCH3, -NH2, -NHCH3, wherein the methyl group is optionally substituted with a substituent selected from halogen, -OH, -OCH3, -NH2, -NHCH3. In another embodiment, R 3 Selected from H, halogens, C 1-4 Alkyl, -OH, -O(C) 1-4 Alkyl group), -NH2, wherein the alkyl group is optionally selected from one or more halogens, -OH, -O (C 1-4 Alkyl groups and -NH2 substituents are used for substitution. In one embodiment, R... 3 The group is selected from H, halogen, methyl, -OH, -OCH3, -NH2, wherein the methyl group is optionally selected from halogen, -OH, -O(C 1-2 Alkyl groups and -NH2 substituents are used for substitution. In one embodiment, R... 3 The group is selected from H, halogen, methyl, -OH, -OCH3, -NH2, wherein the methyl group is optionally substituted with a substituent selected from halogen, -OH, -OCH3, -NH2. In one embodiment, R 3 Selected from H, halogens, methyl, -OH, -NH2. In another embodiment, R 3 Selected from H, halogens, C 1-4 Alkyl, -OH, -O(C) 1-4 Alkyl group), wherein the alkyl group is optionally composed of one or more elements selected from halogens, -OH, -O (C 1-4 The alkyl group is substituted. In one embodiment, R 3 The group is selected from H, halogen, methyl, -OH, -OCH3, wherein the methyl group is optionally selected from halogen, -OH, -O(C 1-2 The alkyl group is substituted. In one embodiment, R 3 The group is selected from H, halogen, methyl, -OH, -OCH3, wherein the methyl group is optionally substituted with a substituent selected from halogen, -OH, -OCH3. In one embodiment, R 3 Selected from H, halogens, methyl groups, and -OH. In yet another embodiment, R... 3 Selected from H, halogens, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 Alkyl)2, Substituted C 1-4Alkyl, wherein the substituted C 1-4 The alkyl group is selected from one or more halogens, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 The alkyl group is substituted. In one embodiment, R... 3 Selected from H, halogens, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, and substituted methyl groups, wherein the substituted methyl group is selected from halogens, -OH, -O(C 1-2 alkyl), -NH(C) 1-2 alkyl), -N(C) 1-2 The alkyl group is substituted. In one embodiment, R... 3 The group is selected from H, halogens, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, and substituted methyl groups, wherein the substituted methyl group is substituted by a substituent selected from halogens, -OH, -OCH3, -NHCH3, and -N(CH3)2. In one embodiment, R 3 The component is selected from H, halogen, -OH, -NH2, and methyl, wherein the methyl group is substituted with -N(CH3)2. In yet another embodiment, R 3 Selected from H, halogens, -OH, -O(C) 1-4 Alkyl), substituted C 1-4 Alkyl, wherein the substituted C 1-4 Alkyl groups are selected from one or more halogens, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 The alkyl group is substituted. In one embodiment, R... 3 Selected from H, halogens, -OH, -OCH3, and substituted methyl groups, wherein the substituted methyl group is selected from halogens, -OH, -O(C 1-2 alkyl), -NH(C) 1-2 alkyl), -N(C) 1-2 The alkyl group is substituted. In one embodiment, R... 3 The group is selected from H, halogens, -OH, -OCH3, and substituted methyl groups, wherein the substituted methyl group is replaced by a substituent selected from halogens, -OH, -OCH3, -NHCH3, and -N(CH3)2. In one embodiment, R 3 The component is selected from H, halogen, -OH, and methyl, wherein the methyl group is substituted with -N(CH3)2. In another embodiment, R 3 Selected from H, halogens, -OH, -O(C) 1-4 Alkyl), substituted C 1-4 Alkyl, wherein the substituted C1-4 The alkyl group is selected from one or more halogens, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 The alkyl group is substituted. In one embodiment, R... 3 Selected from H, halogens, -OH, C 1-2 Alkyl groups, wherein the alkyl group is selected from one or more halogens, -NH(C 1-2 alkyl), -N(C) 1-2 The alkyl group is substituted. In one embodiment, R... 3 Selected from H, halogen, -OH, methyl, wherein the methyl group is selected from halogen, -NH(C 1-2 alkyl), -N(C) 1-2 The alkyl group is substituted. In one embodiment, R... 3 The group is selected from H, halogen, -OH, and methyl, wherein the methyl group is substituted with a substituent selected from halogen, -NHCH3, and -N(CH3)2. In one embodiment, R 3 The component is selected from H, halogen, -OH, and methyl, wherein the methyl group is substituted with -N(CH3)2. In yet another embodiment, R 3 Selected from H, halogens, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 Alkyl), substituted C 1-4 Alkyl, wherein the substituted C 1-4 Alkyl groups are selected from one or more halogens, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 The alkyl group is substituted. In one embodiment, R 3 Selected from H, halogens, -OH, -OCH3, -NH2, -NHCH3, and substituted methyl groups, wherein the substituted methyl group is selected from halogens, -OH, -O(C 1-2 alkyl), -NH(C) 1-2 The alkyl group is substituted. In one embodiment, R 3 The group is selected from H, halogens, -OH, -OCH3, -NH2, -NHCH3, and substituted methyl groups, wherein the substituted methyl group is replaced by a substituent selected from halogens, -OH, -OCH3, and -NHCH3. In one embodiment, R 3 The component is selected from H, halogen, -OH, -NH2, and methyl, wherein the methyl group is substituted with -N(CH3)2. In yet another embodiment, R 3 Selected from H, halogens, -OH, -O(C) 1-4 Alkyl), substituted C 1-4 Alkyl, wherein the substituted C 1-4Alkyl groups are selected from one or more halogens, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 The alkyl group is substituted. In one embodiment, R 3 Selected from H, halogens, -OH, -OCH3, and substituted methyl groups, wherein the substituted methyl group is selected from halogens, -OH, -O(C 1-2 alkyl), -NH(C) 1-2 The alkyl group is substituted. In one embodiment, R 3 The group is selected from H, halogens, -OH, -OCH3, and substituted methyl groups, wherein the substituted methyl group is replaced by a substituent selected from halogens, -OH, -OCH3, and -NHCH3. In one embodiment, R 3 The component is selected from H, halogen, -OH, and methyl, wherein the methyl group is substituted with -N(CH3)2. In another embodiment, R 3 Selected from H, halogens, -OH, -O(C) 1-4 Alkyl), substituted C 1-4 Alkyl, wherein the substituted C 1-4 The alkyl group is selected from one or more halogens, -NH2, -NH(C) 1-4 The alkyl group is substituted. In one embodiment, R 3 Selected from H, halogens, -OH, C 1-2 Alkyl groups, wherein the alkyl group is selected from one or more halogens, -NH(C 1-2 The alkyl group is substituted. In one embodiment, R 3 Selected from H, halogen, -OH, methyl, wherein the methyl group is selected from halogen, -NH(C 1-2 The alkyl group is substituted. In one embodiment, R 3 The group is selected from H, halogen, -OH, and methyl, wherein the methyl group is substituted with a substituent selected from halogen and -NHCH3. In one embodiment, R 3 Selected from H, F, Cl, methyl, -OH, -NH2. In another embodiment, R 3 Selected from H, F, methyl, -OH, -NH2. In one embodiment, R 3 For H. In one implementation, R 3 It is -OH. In one embodiment, R 3 It is CH3.

[0303] In one implementation scheme, R 4 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C)1-6 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 The alkyl group is substituted. In one embodiment, R... 4 Selected from H, halogens, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 Alkyl)2, Substituted C 1-4 Alkyl, wherein the substituted C 1-4 Alkyl groups are selected from one or more halogens, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 The alkyl group is substituted. In one embodiment, R... 4 Selected from H, halogens, -OH, -O(C) 1-3 Alkyl groups, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2, Substituted C 1-3 Alkyl, wherein the substituted C 1-3 Alkyl groups are optionally surrounded by one or more elements selected from halogens, -OH, -O(C). 1-2 Alkyl groups, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 The alkyl group is substituted. In one embodiment, R... 4 Selected from H, halogens, -OH, -NH2, -NH(C) 1-4 Alkyl), substituted C 1-4 Alkyl, substituted -O(C) 1-4 Alkyl), substituted -N(C) 1-4 alkyl)2, wherein the substituted C 1-4 Alkyl, substituted -O(C) 1-4 Alkyl) and substituted -N(C) 1-4 Alkyl group 2 is selected from one or more halogens, -OH, -O(C) 1-2 Alkyl groups, -NH2, -NH(C) 1-4 The alkyl group is substituted. In one embodiment, R 4 Selected from H, halogens, -OH, -O(C) 1-2 Alkyl groups, -NH2, -NH(C) 1-2 Alkyl), substituted C 1-2 Alkyl, substituted -O(C) 1-2 alkyl), wherein the substituted C1-2 Alkyl and substituted -O(C) 1-2 Alkyl groups are selected from one or more halogens, -OH, -O (C 1-2 Alkyl groups, -NH2, -NH(C) 1-2 The alkyl group is substituted. In one embodiment, R 4 Selected from H, halogens, -OH, -OCH3, -NH2, -NHCH3, and substituted C 1-2 Alkyl, wherein the substituted C 1-2 The alkyl group is substituted with one or more substituents selected from halogens, -OH, -OCH3, -NH2, and -NHCH3. In one embodiment, R 4 Selected from H, halogens, -OH, -NH2, -NH(C) 1-4 Alkyl), substituted C 1-4 Alkyl, wherein the substituted C 1-4 Alkyl groups are selected from one or more halogens, -OH, -OCH3, -NH2, -NH(C 1-4 The alkyl group is substituted. In one embodiment, R 4 Selected from H, halogens, -OH, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 Alkyl)2, Substituted C 1-2 Alkyl, wherein the substituted C 1-2 Alkyl groups are selected from one or more halogens, -OH, -O(C) 1-2 Alkyl groups, -NH2, -NH(C) 1-2 The alkyl group is substituted. In one embodiment, R 4 Selected from H, halogens, -OH, -NH2, -NHCH3, and substituted C 1-2 Alkyl, wherein the substituted C 1-2 The alkyl group is substituted with one or more substituents selected from halogens, -OH, -OCH3, -NH2, and -NHCH3. In one embodiment, R 4 Selected from H, halogens, C 1-4 Alkyl, -OH, -O(C) 1-4 Alkyl group), wherein the alkyl group is optionally composed of one or more elements selected from halogens, -OH, -O (C 1-4 Alkyl groups, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 The alkyl group is substituted. In one embodiment, R... 4 Selected from H, halogens, C 1-2Alkyl, -OH, -OCH3, wherein the alkyl group is optionally substituted with one or more substituents selected from halogens, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2. In one embodiment, R 4 Selected from H, halogens, C 1-4 Alkyl, -OH, -O(C) 1-4 Alkyl), -NH2, -NH(C 1-4 alkyl), -N(C) 1-4 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-4 The alkyl group is substituted. In one embodiment, R 4 Selected from H, halogens, C 1-2 Alkyl, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, wherein the alkyl group is optionally substituted with one or more substituents selected from halogens, -OH, and -OCH3. In one embodiment, R 4 Selected from H, halogens, C 1-4 Alkyl, -OH, -O(C) 1-4 Alkyl group), wherein the alkyl group is optionally composed of one or more elements selected from halogens, -OH, -O (C 1-4 The alkyl group is substituted. In one embodiment, R 4 Selected from H, halogens, C 1-2 Alkyl, -OH, -OCH3, wherein the alkyl group is optionally substituted with one or more substituents selected from halogens, -OH, -OCH3. In one embodiment, R 4 Selected from H, -OH, -OCH3. In one embodiment, R 4 For H. In one implementation, R 4 It is -OH.

[0304] In one implementation scheme, R 5 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Alkyl group), wherein the alkyl group is optionally composed of one or more elements selected from halogens, -OH, -O (C1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 The alkyl group is substituted. In one embodiment, R 5 Selected from H, halogens, C 1-4 Alkyl, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 The alkyl group is substituted. In one embodiment, R... 5 Selected from H, halogens, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 Alkyl)2、-C(=O)O(C 1-4 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-4 Alkyl), -C(=O)N(C 1-4 Alkyl)2、-OC(=O)(C 1-4 Alkyl), -NC (=O) (C 1-4 Alkyl)2、-C(=O)(C 1-4 Alkyl), substituted C 1-4 Alkyl, wherein the substituted C 1-4 Alkyl groups are selected from one or more halogens, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 Alkyl)2、-C(=O)O(C 1-4 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-4 Alkyl), -C(=O)N(C 1-4 Alkyl)2、-OC(=O)(C 1-4 Alkyl), -NC (=O) (C 1-4 Alkyl)2、-C(=O)(C1-4 The alkyl group is substituted. In one embodiment, R 5 Selected from H, halogens, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 Alkyl)2, Substituted C 1-4 Alkyl, wherein the substituted C 1-4 Alkyl groups are selected from one or more halogens, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 The alkyl group is substituted. In one embodiment, R... 5 Selected from H, halogens, -O(C) 1-4 alkyl), -NH(C) 1-4 alkyl), -N(C) 1-4 Alkyl)2, Substituted C 1-2 Alkyl, wherein the substituted C 1-2 Alkyl groups are selected from one or more halogens, -O(C) 1-4 alkyl), -NH(C) 1-4 alkyl), -N(C) 1-4 The alkyl group is substituted. In one embodiment, R... 5 Selected from H, halogens, -O(C) 1-4 alkyl), -NH(C) 1-4 alkyl), -N(C) 1-4 Alkyl)2, Substituted C 1-2 Alkyl, wherein the substituted C 1-2 The alkyl group is substituted with one or more substituents selected from halogens, -OCH3, -NHCH3, and -N(CH3)2. In one embodiment, R 5 Selected from H, halogens, -O(C) 1-2 alkyl), -NH(C) 1-2 alkyl), -N(C) 1-2 Alkyl)2, Substituted C 1-2 Alkyl, wherein the substituted C 1-2 The alkyl group is substituted by one or more substituents selected from halogens, -OCH3, -NHCH3, and -N(CH3)2.

[0305] In one implementation scheme, R 6 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 The alkyl group is substituted. In another embodiment, R 6 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, wherein the alkyl group is optionally substituted with one or more substituents selected from halogens, -OH, and -NH2. In one embodiment, R 6 Selected from H, halogens, -NO2, -CN, C 1-2 Alkyl, -OH, -O(C) 1-2 Alkyl groups, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 Alkyl group 2, wherein the alkyl group is optionally substituted with one or more substituents selected from halogens, -OH, and -NH2. In yet another embodiment, R 6 Selected from H, halogens, -NO2, -CN, C 1-4 Alkyl, -OH, -O(C) 1-4 Alkyl groups, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 Alkyl)2, wherein the alkyl group is optionally substituted with one or more halogens. In another embodiment, R 6 Selected from H, halogens, -NO2, -CN, C 1-2 Alkyl, -OH, -O(C) 1-2 Alkyl groups, -NH2, -NH(C) 1-4 alkyl), -N(C) 1-4 Alkyl)2. In one embodiment, R 6 Selected from H, F, Cl, Br, C 1-6 Alkyl, -OH, -NH2, wherein the alkyl group is optionally substituted with one or more substituents selected from halogens, -OH, -NH2. In another embodiment, R 6 Selected from H, F, Cl, Br, methyl, -OH, -NH2. In a particular embodiment, R 6 It can be H or -OH, especially H.

[0306] In one implementation scheme, R 3 It is methyl, and R 4 Selected from -OH, -NH2, -NH(C) 1-3 alkyl), -N(C)1-3 alkyl)2,-COOH substituted C 1-3 Alkyl, wherein the substituted C 1-3 Alkyl groups are selected from one or more groups chosen from -OH, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 Substituents of alkyl groups (2) and -COOH. In one embodiment, R 3 It is methyl, and R 4 Selected from -NH2, -NH(C 1-3 alkyl), -N(C) 1-3 alkyl)2,-COOH substituted C 1-3 Alkyl, wherein the substituted C 1-3 Alkyl groups are selected from one or more groups chosen from -OH, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 Substitution with alkyl groups (2) and -COOH.

[0307] In another implementation, R 3 It is methyl, and R 5 Selected from -OH, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 alkyl)2,-COOH substituted C 1-3 Alkyl, wherein the substituted C 1-3 Alkyl groups are selected from one or more groups chosen from -OH, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 Substituents of alkyl group (2) and -COOH. In another embodiment, R 3 It is methyl, and R 5 Selected from -NH2, -NH(C 1-3 alkyl), -N(C) 1-3 alkyl)2,-COOH substituted C 1-3 Alkyl, wherein the substituted C 1-3 Alkyl groups are selected from one or more groups chosen from -OH, -NH2, -NH(C) 1-2 alkyl), -N(C) 1-2 Substitution with alkyl groups (2) and -COOH.

[0308] In one implementation scheme, R 14 R 15 R 16 R 17 R 18 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 Cyclic hydrocarbon group), -O (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cyclic hydrocarbon group), -NH (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -NH(C=O) (three- to seven-membered heterocyclic groups), -C(=O) (C 1-6 Alkyl), -C(=O)O(C 1-6 Alkyl), -C(=O)O(C 3-6 cyclic hydrocarbon group), -C(=O)O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -C(=O)O (three- to seven-membered heterocyclic groups), -C(=O)O (C 1-4 Alkylene group (ternary to seven-membered heterocyclic group), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C1-6 Alkyl)2、-C(=O)NH(C 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -C(=O)N(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -C(=O)NH (three- to seven-membered heterocyclic group), -C(=O)N (three- to seven-membered heterocyclic group)2, -C(=O)NH (C 1-4 alkylene-tertiary to seven-membered heterocyclic groups), -C(=O)N(C 1-4 2. Alkylene-tertiary to seven-membered heterocyclic group, wherein the alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, or heterocyclic group is optionally selected from one or more of H, halogen, nitro, cyano, -OH, -SH, -NH2, =O, and -COOH. In one embodiment, R 14 R 15 R 16 R 17 R 18 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OR 7 -NR 7 R 8 -C(=O)OR 7 -C(=O)NR 7 R 8 -OC(=O)R 7 -NC(=O)R 7 R 8 -C(=O)R 7 In one implementation scheme, R 14 R 15 R 16 R 17 R 18 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 Cyclic hydrocarbon group), -O (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cyclic hydrocarbon group), -NH (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -NH (C=O) (three to seven-membered heterocyclic groups). In one embodiment, R 14 R 15 R 17 R 18 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 Cyclic hydrocarbon group), -O (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cyclic hydrocarbon group), -NH (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -NH (C=O) (three to seven-membered heterocyclic groups). In one embodiment, R 14 R 15 R 16 R 17 R 18 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 Cyclic hydrocarbon group), -O (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4 (alkylene)-(ternary to seven-membered heterocyclic group). In one embodiment, R 14 R 15 R 16 R 17 R 18 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 Cyclic hydrocarbon group), -O (C=O)(C 1-4 Alkylene-C 3-6Cyclic hydrocarbon groups), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4 (alkylene)-(ternary to seven-membered heterocyclic group). In one embodiment, R 14 R 15 R 16 R 17 R 18 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OH, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cyclic hydrocarbon group), -NH (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -NH (C=O) (three to seven-membered heterocyclic groups). In one embodiment, R 14 R 15 R 16 R 17 R 18 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OH, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6Alkyl), -NH(C=O)(C 3-6 cyclic hydrocarbon group), -NH (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -NH (C=O) (three to seven-membered heterocyclic groups). In one embodiment, R 14 R 15 R 16 R 17 R 18 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OH, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-NH(C=O)(C 1-6 Alkyl group). In one embodiment, R 14 R 15 R 17 R 18 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OH, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-NH(C=O)(C 1-6 Alkyl group). In one embodiment, R 16 For H. In one implementation, R 16 It is -OCH3.

[0309] Therefore, in one embodiment, formula (I) has the structure of formula (vii), wherein the LCM portion is the structure of formula (7) above (see formula (7) and its embodiments) or a pharmaceutically acceptable salt thereof.

[0310]

[0311] In one implementation, L can be covalently linked to any suitable site of equation (7).

[0312] The structure described in equation (8) falls within the scope of the structures described in equations (1), (3), (6), and (7). In one embodiment, the LCM portion has the structure described in equation (8):

[0313]

[0314] in:

[0315] Y is either O or S;

[0316] C ring, R 2 R 3 R 4 R5 R 6 As defined in equation (7).

[0317] In one implementation, Y is 0. When Y is 0, equation (8) is:

[0318] In a particular embodiment, the structure of formula (8) is selected from compounds A5, A6, and A7:

[0319]

[0320] Therefore, in one embodiment, formula (I) has the structure of formula (viii), wherein the LCM portion is the structure of formula (8) above (see formula (8) and its embodiments) or a pharmaceutically acceptable salt thereof.

[0321]

[0322] In one embodiment, L can be covalently linked to any suitable site of formula (8). Suitable sites include, for example, -OH, etc.

[0323] In one implementation, equation (viii) is

[0324] In a particular implementation, the structure of formula (viii) is selected from:

[0325]

[0326] The structure described in equation (9) falls within the scope of the structures described in equations (1), (3), and (6). In one embodiment, the LCM portion has the structure of equation (9):

[0327]

[0328] in:

[0329] R 19 Each time it appears, it is independently selected from halogen, -NO2, -CN, C. 1-6 Alkyl, -OR 7 -SR 7 -NR 7 R 8 -C(=O)OR 7 -C(=O)NR 7 R 8 -OC(=O)R 7 -NC(=O)R 7 R 8 -C(=O)R 7 -S(=O)2OR7 -S(=O)2R 7 -S(=O)2NR 7 R 8 -OS(=O)2R 7 -NS(=O)2R 7 R 8 -S(=O)R 7 The alkyl group is optionally surrounded by one or more elements selected from halogens, -NO2, -CN, -OH, -O(C). 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution with alkyl groups (2) or -COOH;

[0330] m can be 0, 1, 2, 3, 4, or 5;

[0331] R 2 R 3 R 4 R 5 R 6 As defined in equation (6).

[0332] In one implementation scheme, R 2 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OR a1 -SR a1 -NR a1 R b1 -C(=O)OR a1 -C(=O)NR a1 R b1 -C(=O)R a1 -S(=O)2OR a1 -S(=O)2R a1 -S(=O)2NR a1 R b1 -S(=O)R a1 The alkyl, cyclic, or heterocyclic group is optionally selected from one or more halogens, -NO2, -CN, C 1-6 Alkyl, -OR a2 -SR a2 -NR a2 R b2 -C(=O)OR a2 -C(=O)NR a2 Rb2 -C(=O)R a2 Substituents are substituted. In a preferred embodiment, R 2 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl group, -OH group, wherein the alkyl group is optionally surrounded by one or more elements selected from halogen, -NO2, -CN, C. 1-6 Alkyl, -NR a2 R b2 Substituents are substituted. In a more preferred embodiment, R 2 Selected from H, halogens, C 1-6 Alkyl group, -OH group, wherein the alkyl group is optionally surrounded by one or more elements selected from halogens, C 1-6 Alkyl and -NR a2 R b2 The group is substituted. In a further embodiment, R 2 Selected from H, C 1-4 Alkyl group, -OH group, wherein the alkyl group is optionally composed of one or more molecules selected from -NR. a2 R b2 The group is substituted. In a particular embodiment, R 2 Selected from H, C 1-4 Alkyl group, -OH group, wherein the alkyl group is -CH2[CH(CH3)2], and optionally is selected from one or more groups selected from -NR. a2 R b2 The group is substituted. In another embodiment, R... 2 For -NR a1 R b1 Substituted alkyl group. R a1 R b1 R a2 R b2 As defined in equation (6). In a particular implementation, R 2 for

[0333] In one implementation scheme, R 19 Each time it appears, it is independently selected from halogens and C. 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2 substituents.

[0334] In a particular embodiment, the structure of formula (9) is compound A8:

[0335] Therefore, in one embodiment, formula (I) has the structure of formula (ix) below, wherein the LCM portion is the structure of formula (9) above (see formula (9) and its embodiments) or a pharmaceutically acceptable salt thereof.

[0336]

[0337] In one embodiment, L can be covalently linked to any suitable site of formula (9). Suitable sites include, for example, -NH2, etc.

[0338] In one particular implementation, the structure of formula (ix) is as follows:

[0339] In one embodiment, the structure of the LCM portion is as shown in formula (10), or is a pharmaceutically acceptable salt thereof:

[0340]

[0341] Among them, R 20 The atom is selected from bicyclic heteroaryl groups, having 9-10 ring atoms, including 1-3 heteroatoms each independently selected from oxygen, sulfur, and nitrogen, with the remaining atoms being carbon atoms; the heteroaryl group is unsubstituted or has at least one atom selected from R. X3 Substitution of groups;

[0342] R 21 Selected from C 1-8 alkyl;

[0343] R 22 Selected from R X3 ;

[0344] R 23 It is a phenyl group, which is unsubstituted or contains at least one component selected from R. X3 Substitution of groups;

[0345] R X3 Each time it appears, it is independently selected from C. 1-8 Alkyl, C 1-8 Alkenyl, halogen, -CN, -CF3, -CHF2, -CH2F, -NO2, -OH, -O(C 1-8 Alkyl), -SH, -S(C 1-8 Alkyl groups, -NH2, -NH(C) 1-8 alkyl), -N(C) 1-8 Alkyl group 2, -COOH, -C(=O)O(C 1-8 Alkyl), -C(=O)NH(C1-8 Alkyl), -C(=O)N(C 1-8 Alkyl)2, -S(=O)2OH, -S(=O)2(OC 1-8 Alkyl groups), -S(=O)2NH2, -S(=O)2NH(C 1-8 Alkyl), -S(=O)2N(C 1-8 Alkyl group 2; wherein the alkyl group is optionally composed of one or more elements selected from halogen, -NO2, -CN, C 1-8 Alkyl, -OH, -O(C) 1-8 Alkyl), -SH, -S(C 1-8 Alkyl groups, -NH2, -NH(C) 1-8 alkyl), -N(C) 1-8 Substitution with alkyl groups (2), =O, and -COOH;

[0346] p is 0, 1, or 2.

[0347] In one implementation scheme, R 20 The group is selected from the group consisting of the following bicyclic heteroaryl groups: benzofuranyl, benzothiophenyl, benzoxazolyl, benzoisoxazolyl, benzoimidazolyl, benzotriazolyl, indazole, indole, and isoyindole; and the heteroaryl group is unsubstituted or is composed of at least one group selected from C. 1-8 Alkyl groups are substituted.

[0348] In one implementation scheme, R 22 Selected from C 1-8 Alkyl, halogen, and -CN.

[0349] In one implementation, p is 0.

[0350] In a particular embodiment, the structure of formula (10) is compound A9 or A9':

[0351]

[0352] Therefore, in one embodiment, formula (I) has the structure of formula (x) below, wherein the LCM portion is the structure of formula (10) above (see formula (10) and its embodiments above) or a pharmaceutically acceptable salt thereof.

[0353]

[0354] In one embodiment, L can be covalently linked to any suitable site of formula (10). Suitable sites include, for example, -S(O)2OH, etc.

[0355] In a particular implementation, the structure of equation (x) is as follows:

[0356]

[0357] In one embodiment, the structure of the LCM portion is as shown in formula (11), or is a pharmaceutically acceptable salt thereof:

[0358]

[0359] Among them, R 24 Selected from ternary to 7-membered heterocyclic groups; said heterocyclic group is unsubstituted or substituted with at least one group selected from R X3 Substitution of groups;

[0360] L 3 Choose any C 1-8 alkylene and a C 3-6 Combinations of cycloalkyl groups;

[0361] R 25 Selected from H, C 1-8 alkyl;

[0362] R 26 Selected from halogens, -NO2, -CN, C 1-8 Alkyl, -OH, -O(C) 1-8 Alkyl), -SH, -S(C 1-8 Alkyl groups, -NH2, -NH(C) 1-8 alkyl), -N(C) 1-8 Alkyl)2;

[0363] L 4 Selected from C 1-8 Alkylene and C 1-8 alkoxy subunit;

[0364] R 27 It is a phenyl group, which is unsubstituted or contains at least one component selected from R. X3 Substitution of groups;

[0365] q is 0, 1, or 2;

[0366] R X3 As defined in equation (10).

[0367] In one implementation scheme, R 24 The heterocyclic group is selected from five- to six-membered heterocyclic groups, preferably pyrrolidinyl; and the heterocyclic group is unsubstituted or is composed of at least one group selected from C. 1-8 Alkyl groups are substituted.

[0368] In one implementation scheme, L 3 for

[0369] In one implementation scheme, q is 1.

[0370] In a particular embodiment, the structure of formula (11) is compound A10:

[0371]

[0372] Therefore, in one embodiment, formula (I) has the structure of formula (xi), wherein the LCM portion is the structure of formula (11) above (see formula (11) and its embodiments above) or a pharmaceutically acceptable salt thereof.

[0373]

[0374] In one embodiment, L can be covalently linked to any suitable site of formula (11). Suitable sites include, for example, -NH2, etc.

[0375] In a particular implementation, the structure of formula (xi) is as follows:

[0376]

[0377] In one embodiment, the structure of the LCM portion is as shown in formula (12), or is a pharmaceutically acceptable salt thereof:

[0378]

[0379] Among them, R 28 C 1-8 alkenyl; the alkenyl group is formed by at least one C 1-8 Alkyl substitution, wherein the alkyl group is optionally replaced by one or more selected from R X4 Substitution of groups;

[0380] R 29 Selected from H, C 1-8 alkyl;

[0381] R 30 Selected from halogens, -NO2, -CN, C 1-8 Alkyl, -OH, -O(C) 1-8 Alkyl), -SH, -S(C 1-8 Alkyl groups, -NH2, -NH(C) 1-8 alkyl), -N(C) 1-8 Alkyl)2;

[0382] L 5 Selected from -O-, C 1-8 Alkylene and C 1-8 alkoxy subunit;

[0383] R 31Selected from six-membered heteroaryl groups, having six ring atoms, including one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen, with the remaining ring atoms being carbon atoms, wherein the heteroaryl group is unsubstituted or has at least one heteroatom selected from R. X3 Substitution of groups;

[0384] r can be 0, 1, 2, 3, or 4;

[0385] s can be 0, 1, 2, 3, or 4;

[0386] R X4 Each time it appears, it is independently selected from C. 1-8 Alkyl, C 1-8 Alkenyl, halogen, -CN, -CF3, -CHF2, -CH2F, -NO2, -O(C 1-8 alkyl), -S(C 1-8 alkyl), -NH(C) 1-8 alkyl), -N(C) 1-8 Alkyl)2、-OC(=O)(C 1-8 Alkyl), -NHC(=O)(C 1-8 Alkyl), -NC (=O) (C 1-8 Alkyl)2, -OS(=O)2(C 1-6 Alkyl), -NHS(=O)2(C 1-8 alkyl), -N(C) 1-8 Alkyl)S(=O)2(C 1-8 Alkyl group; wherein the alkyl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, C 1-8 Alkyl, -OH, -O(C) 1-8 Alkyl), -SH, -S(C 1-8 Alkyl groups, -NH2, -NH(C) 1-8 alkyl), -N(C) 1-8 Substitution with alkyl groups (2), =O, and -COOH;

[0387] R X3 As defined in equation (10).

[0388] In one implementation scheme, R 29 For H.

[0389] In one implementation scheme, R 31 The pyridyl group is preferred, preferably pyridin-3-yl, and the pyridyl group is unsubstituted or has at least one component selected from C. 1-8 Alkyl substituents.

[0390] In one implementation scheme, R X4 Selected from -O(C 1-8 Alkyl), preferably -O(C)1-3 Alkyl groups, especially methoxy groups.

[0391] In one implementation scheme, R 28 for

[0392] In one implementation, r is 1.

[0393] In a particular embodiment, the structure of formula (12) is compound A11:

[0394]

[0395] Therefore, in one embodiment, formula (I) has the structure of formula (xii), wherein the LCM portion is the structure of formula (12) above (see formula (12) and its embodiments above) or a pharmaceutically acceptable salt thereof.

[0396]

[0397] In one implementation, L can be covalently linked to any suitable site of equation (12).

[0398] In a particular implementation, the structure of formula (xii) is as follows:

[0399]

[0400] In one embodiment, the structure of the LCM portion is as shown in formula (13), or is a pharmaceutically acceptable salt thereof:

[0401]

[0402] Among them, R 32 Selected from ternary to 7-membered heterocyclic groups; said heterocyclic group is unsubstituted or substituted with at least one group selected from R X3 Substitution of groups;

[0403] L 6 Selected from -O-, C 1-8 Alkylene and C 1-8 alkoxy subunit;

[0404] R 33 R 34 Selected from halogens, C 1-8 alkyl;

[0405] R 35 Selected from halogens, -NO2, -CN, C 1-8 Alkyl, -OH, -O(C) 1-8 Alkyl), -SH, -S(C 1-8 Alkyl groups, -NH2, -NH(C) 1-8alkyl), -N(C) 1-8 Alkyl)2;

[0406] R 36 The compound is selected from five-membered heteroaryl groups, which have five ring atoms, including one to three heteroatoms each independently selected from oxygen, sulfur, and nitrogen, and the remaining atoms are carbon atoms. The heteroaryl group is unsubstituted or has at least one heteroatom selected from R. X3 Substitution of groups;

[0407] t can be 0, 1, 2, or 3;

[0408] u can be 0, 1, 2, 3 or 4;

[0409] R X3 As defined in equation (10).

[0410] In one implementation scheme, R 32 The heterocyclic group is selected from five- to six-membered heterocyclic groups, preferably pyrrolidinyl, imidazoalkyl, pyrazolyl, tetrahydropyranyl, piperidinyl, morpholinyl, thiomorpholinyl, or piperazineyl, and the heterocyclic group is unsubstituted or substituted with at least one of the following: halogen, C 1-8 Alkyl groups are substituted.

[0411] In one implementation scheme, R 36 The group consisting of the following five-membered heteroaryl groups: pyrrole, oxazolyl, thiazolyl, imidazole, pyrazolyl, isoxazolyl, and isothiazolyl, wherein the heteroaryl group is unsubstituted or is composed of at least one group selected from C. 1-8 Alkyl groups are substituted.

[0412] In one implementation, t is 0. In another implementation, u is 0.

[0413] In a particular embodiment, the structure of formula (13) is compound A12:

[0414]

[0415] Therefore, in one embodiment, formula (I) has the structure of formula (xiii), wherein the LCM portion is the structure of formula (13) above (see formula (13) and its embodiments above) or a pharmaceutically acceptable salt thereof.

[0416]

[0417] In one implementation, L can be covalently linked to any suitable site of equation (13).

[0418] In a particular implementation, the structure of equation (xiii) is as follows:

[0419]

[0420] In one embodiment, the structure of the LCM portion is as shown in formula (14), or is a pharmaceutically acceptable salt thereof:

[0421]

[0422] Among them, R 37 Selected from six-membered heteroaryl groups, having six ring atoms, including one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen, with the remaining atoms being carbon atoms. The heteroaryl group is unsubstituted or substituted with at least one atom selected from halogen, -NO2, -CN, or C. 1-8 Alkyl, -OH, -O(C) 1-8 Alkyl), -SH, -S(C 1-8 Alkyl groups, -NH2, -NH(C) 1-8 alkyl), -N(C) 1-8 Substitution of alkyl groups;

[0423] R 38 R 39 R 40 Each independently selected from R X3 ;

[0424] R 41 The compound is selected from five-membered heteroaryl groups, which have five ring atoms, including one to three heteroatoms each independently selected from oxygen, sulfur, and nitrogen, and the remaining atoms are carbon atoms. The heteroaryl group is unsubstituted or has at least one heteroatom selected from R. X3 Substitution of groups;

[0425] v can be 0, 1, 2, or 3;

[0426] w can be 0, 1, 2, 3, or 4;

[0427] x is 0, 1, 2, 3 or 4;

[0428] R X3 As defined in equation (10).

[0429] In one implementation scheme, R 37 The group is selected from the group consisting of the following six-membered heteroaryl groups: pyridyl, pyrimidinyl, pyridazinyl, preferably pyrimidinyl, more preferably pyrimidin-4-yl; and the six-membered heteroaryl group is unsubstituted or is substituted by at least one group selected from halogen, -CN, C. 1-8 Alkyl, -OH, -O(C) 1-8 Alkyl groups, -NH2, -NH(C) 1-8 alkyl), -N(C) 1-8 Alkyl group substitution.

[0430] In one implementation scheme, R 41The group is selected from the group consisting of the following five-membered heteroaryl groups: thienyl, furanyl, pyrroleyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, preferably thienyl or furanyl, more preferably thienyl, especially thien-2-yl; and the five-membered heteroaryl group is unsubstituted or is composed of at least one group selected from halogen, -CN, and C. 1-8 Alkyl groups are substituted.

[0431] In one embodiment, v is 0. In another embodiment, w is 0. In one embodiment, x is 0.

[0432] In a particular embodiment, the structure of formula (14) is compound A13:

[0433]

[0434] Therefore, in one embodiment, formula (I) has the structure of formula (xiv), wherein the LCM portion is the structure of formula (14) above (see formula (14) and its embodiments above) or a pharmaceutically acceptable salt thereof.

[0435]

[0436] In one embodiment, L can be covalently linked to any suitable site of formula (14). Suitable sites include, for example, -NH2, etc.

[0437] In a particular implementation, the structure of formula (xiv) is as follows:

[0438]

[0439] L connector

[0440] L is a chemical bond or group used to connect the LCM portion and the TM portion. In one embodiment, L is rigid or flexible. In a preferred embodiment, L is flexible. In one embodiment, L is a chemical bond. In another embodiment, L is a straight or branched hydrocarbon chain containing 1-60, preferably 1-30, more preferably 2-16 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16) carbon atoms, wherein each carbon atom may optionally be replaced by one or more, for example 1-3, preferably 1-2, particularly 1 heteroatom; wherein the heteroatom is selected from oxygen, sulfur, nitrogen, phosphorus, preferably oxygen, sulfur or nitrogen, more preferably oxygen or nitrogen, particularly oxygen; wherein the carbon atom or heteroatom is optionally replaced by one or more selected from R L1 R L2 R L3 R L4 and R L5 The group is substituted; wherein

[0441] R L1 R L2 R L3 R L4 and R L5 Each is independently selected from: H, halogen, C 1-6 Alkyl, -O(C) 1-6 alkyl), -S(C 1-6 alkyl), -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, C 3-6 cycloalkyl, C 6-10 Aryl, five- to seven-membered heteroaryl, three- to seven-membered heterocyclic, -O(C 3-6 cycloalkyl), -S(C 3-6 cycloalkyl), -NH(C 3-6 cycloalkyl), -N(C) 3-6 cycloalkyl)2, -N(C 3-6 cycloalkyl)(C 1-6 Alkyl groups, -OH, -NH2, -SH, -S(=O)2(C 1-6 Alkyl), -P(=O)(OC 1-6 Alkyl)(C 1-6 Alkyl), -P(=O)(OC 1-6 Alkyl)2、-C≡CC 1-6 Alkyl group, -C≡CH, -CH=CH(C) 1-6 alkyl), -C(C 1-6 Alkyl)=CH(C 1-6 alkyl), -C(C 1-6 Alkyl) = C(C 1-6 Alkyl group 2, -Si(OH)3, -Si(C) 1-6 Alkyl)3、-Si(OH)(C 1-6 Alkyl)2、-C(=O)(C 1-6 Alkyl groups, -COOH, halogens, -CN, -CF3, -CHF2, -CH2F, -NO2, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl), -S(=O)N(C 1-6 Alkyl)2、-C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(=O)NH(C 1-6 alkyl), -N(C) 1-6 Alkyl)C(=O)N(C1-6 Alkyl)2、-NHC(=O)NH(C 1-6 Alkyl), -NHC(=O)N(C 1-6 Alkyl)2, -NHC(=O)NH2, -N(C 1-6 alkyl)S(=O)2NH(C 1-6 alkyl), -N(C) 1-6 Alkyl)S(=O)2N(C 1-6 alkyl)2、-NHS(=O)2NH(C 1-6 Alkyl), -NHS(=O)2N(C 1-6 Alkyl group)2 and NHS(=O)2NH2. The heteroatom can be located in the middle of the chain, or at one or both ends of the chain. When the heteroatom is at the end, it indicates that the linker is connected to the LCM and / or TM portions through that heteroatom. In one embodiment, L is a straight-chain group.

[0442] In another embodiment, L is a structure of formula (a) or a pharmaceutically acceptable salt thereof:

[0443] -Dy-(a)

[0444] Where y is an integer greater than 1; and

[0445] Each D is independently selected from the following groups: key, -CR L1 R L2 -, -O-, -S-, -S(=O)-, S(=O)2-, -NR L3 -、-S(=O)2NR L3 -、-S(=O)NR L3 -、-C(=O)NR L3 -、-NR L3 C(=O)NR L4 -、-NR L3 S(=O)2NR L4 -、-C(=O)-、-CR L1 =CR L2 -、-C≡C-、-SiR L1 R L2 -、-P(=O)R L1 -、-P(=O)OR L1 - Choose any location with a radius of 0-6 R. L1 and / or R L2 C with substituent group 3-6 cycloalkyl, optionally hydroxylated by 0-6 R L1 and / or R L2 Group-substituted tri- to seven-membered heterocyclic groups, optionally via 0-6 R groups L1 and / or RL2 Group-substituted aryl groups, optionally via 0-6 R groups L1 and / or R L2 Group-substituted heteroaryl groups; wherein

[0446] When y is greater than 1, R L1 or R L2 Each can independently link to another D group to form a structure that can be further linked via 0-4 R groups. L5 A cyclic alkyl and / or heterocyclic moiety substituted with a group. y is an integer less than or equal to 30. In one embodiment, y is an integer less than or equal to 20, preferably less than or equal to 16, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16. In one embodiment, y is an integer less than or equal to 12.

[0447] In one implementation scheme, D is independently selected from -CR L1 R L2 -、-O- and -NR L3 - In one implementation scheme, R L1 R L2 and R L3 For H. In a particular embodiment, the structure of L is as follows: In one implementation scheme, D is independently selected from -CR L1 R L2 - In a particular implementation, the structure of L is In one particular implementation, y is 12, and D is selected from -CR L1 R L2 - and -O-. In one implementation, R L1 and R L2 For H. In another particular embodiment, the structure of L is

[0448] In one particular implementation, D is independently selected from -C (=O)-, optionally via 0-6 R... L1 and / or R L2 Group-substituted heteroaryl, -O-, -CR L1 R L2 - Choose any location with a radius of 0-6 R. L1 and / or R L2 Group-substituted ternary to 7-membered heterocyclic groups and -NR L3 In one implementation scheme, each R L1 R L2 and R L3 For H. In a particular embodiment, the structure of L is

[0449] TM part

[0450] In one embodiment, the lipid droplet binding portion is a portion capable of non-covalently interacting with the lipid droplet.

[0451] In one embodiment, the lipid droplet-binding portion is a neutral lipid bound to the lipid droplet. In a specific embodiment, the neutral lipid bound to the lipid droplet is selected from steroids and steroid esters. It should be understood that the neutral lipid bound to the lipid droplet can also be an analogue of neutral lipids stored in the lipid droplet. In another embodiment, the neutral lipid bound to the lipid droplet is an analogue of neutral lipids stored in the lipid droplet. In a specific embodiment, the analogue of the neutral lipid is selected from cholesterol ester analogues stored in the lipid droplet.

[0452] In one embodiment, the TM portion is a known lipid droplet probe, a compound capable of binding to lipid droplet-labeled proteins, or a compound capable of binding to neutral lipids in lipid droplets. In one embodiment, the lipid droplet probe is selected from lipid droplet-specific probes and probes that preferentially target lipid droplets in cells, preferably lipid droplet-specific probes. In another embodiment, the lipid droplet probe is selected from dye molecules that are affinity for lipid droplets. In one embodiment, the lipid droplet probe is lipophilic or amphiphilic. In yet another embodiment, the lipid droplet probe is selected from lipophilic dye molecules that are affinity for neutral lipids. In a specific embodiment, the TM portion is an azo dye that is affinity for lipid droplets. In a particular embodiment, the azo dye that is affinity for lipid droplets is selected from Sudan I, Sudan II, Sudan III, Oil Red BB, Oil Red O, Sudan Red G, and Sudan Black B, preferably Sudan III, Oil Red O, and Oil Red BB. In yet another particular embodiment, the azo dye that is affinity for lipid droplets is Oil Red BB. In one specific implementation scheme, the lipid droplet probe is selected from Sudan I, Sudan II, Sudan III, Oil Red BB, Oil Red O, Sudan Red G, Sudan Black B, Nile Red, 493 / 503, monodanthyl pentane, PyrPy10d, PyrPy11c, PITE, TPE-AmAl, TPA-BI, LipidGreen, LipidGreen2, LD540, AF8, AF10, AFN, NAP AIEgen dye, LD-BTD1, LipiDye, Phos2a, Phos 2b, Phos 3a, Phos 3b, SF44, SF58, FAS, DPAS, BTD-coumarin hybrid, IND-TPA, photoactivated AIE probe, LD-TPZn, LQD, photoactivated AIEgen probe (e.g., PhotoAFN 2a-c), TPE-AC, TPMN, TTMN, MeTTMN, MeOTTMN, DCMa, DCI, DCFu, NLV-1, StatoMerocynaine dye (SMCy dye). In one particular embodiment, the NAP AIEgen dye is selected from NAP-Ph, NAP-Br, NAP-CF3, and NAP-Py. In one particular embodiment, the BTD-coumarin hybrid is BTD-Lip. In one particular embodiment, the photoactivated AIE probe is BZT 3a. In one particular embodiment, the photoactivated AIE probe is BZT 4a. In one particular embodiment, the photoactivated AIEgen probe is PhotoAFN 2a-c. In one particular embodiment, the SMCy dye is selected from SMCy 3 and SMCy 5.5. In a preferred embodiment, the lipid droplet probe selectively binds to lipid droplets. In another preferred embodiment, the lipid droplet probe selectively binds to neutral lipids stored in lipid droplets.

[0453] Some exemplary lipid droplet probes are selected from the structures shown in the figure below:

[0454]

[0455]

[0456]

[0457]

[0458] LQD refers to the lipophilic quantum dot reported by Mandal et al. (“Quantum Dot-Based Designed Nanoprobe for Imaging Lipid Droplet”, J. Phys. Chem. C 2017, 121, 42, 23727-23735). LQD·TPMN, LQD·TTMN, LQD·MeTTMN, and LQD·MeOTTMN are quantum dot-based fluorescent probes.

[0459] In one specific implementation, the lipid droplet probe is

[0460]

[0461] In one specific embodiment, the lipid droplet probe is selected from cholesterol with a visual group, cholesterol esters with a visual group, and triglycerides with a visual group. The visual group may be a fluorescent group. In another specific embodiment, the lipid droplet probe is selected from cholesterol with a luminescent group, cholesterol esters with a luminescent group, and triglycerides with a luminescent group. The luminescent group may be a fluorescent group.

[0462] In another specific embodiment, the lipid droplet probe is selected from the following molecules (available from Invitrogen).

[0463]

[0464]

[0465]

[0466] In another specific embodiment, the lipid droplet probe is selected from the following molecules (available from Invitrogen).

[0467]

[0468] In a preferred embodiment, the lipid droplet probe is selected from:

[0469]

[0470]

[0471]

[0472] In one embodiment, the TM portion has the structure of the following formula (II).

[0473]

[0474] in:

[0475] The E ring and F ring are each independently selected from the benzene ring and the naphthalene ring; wherein the E ring is optionally composed of one or more rings selected from the R ring. E The F ring is optionally replaced by one or more groups selected from R. F The G ring is optionally replaced by one or more groups selected from R. G Substitution of groups;

[0476] The G ring is absent, or is selected from the benzene ring and the naphthalene ring;

[0477] Z 1 It is an azo group;

[0478] Z 2 It does not exist, or it may be an azo group;

[0479] R E R F and R G Each occurrence is independently selected from H, halogen, -NO2, -CN, =O, =S, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 Cyclic hydrocarbon group), -O (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 alkyl), -N(C) 1-6 alkyl)-(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cyclic hydrocarbon group), -N(C) 1-6 alkyl)-(C=O)(C 3-6 cyclic hydrocarbon group), -NH (C=O)(C 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-6 alkyl)-(C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -NH (C=O) (three- to seven-membered heterocyclic groups), -N (C 1-6 Alkyl)-(C=O) (three to seven-membered heterocyclic groups), -COOH, -C(=O) (C 1-6 Alkyl), -C(=O)O(C 1-6 Alkyl), -C(=O)O(C 3-6 cyclic hydrocarbon group), -C(=O)O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -C(=O)O (three- to seven-membered heterocyclic groups), -C(=O)O (C 1-4 Alkylene group (ternary to seven-membered heterocyclic group), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-C(=O)NH(C 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -C(=O)N(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -C(=O)NH (three- to seven-membered heterocyclic group), -C(=O)N (three- to seven-membered heterocyclic group)2, -C(=O)NH (C 1-4alkylene-tertiary to seven-membered heterocyclic groups), -C(=O)N(C 1-4 alkylene-tertiary to heptaneous groups) 2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl), -S(=O)N(C 1-6 Alkyl)2, wherein the alkyl, alkylene, alkenyl, alkynyl, cycloalkyl or heterocyclic group is optionally selected from one or more halogens, nitro, cyano, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Substitution of alkyl group 2; or

[0480] Two Rs E Two Rs F Or two Rs G They are interconnected, forming carbon together with the atoms they are connected to. 3-10 Hydrocarbon ring or three- to seven-membered heterocycle, wherein the hydrocarbon ring or heterocycle is optionally surrounded by one or more elements selected from halogen, nitro, cyano, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2 substituents. When Z 2 When not present, the G ring and F ring are connected by a bond.

[0481] Therefore, in one embodiment, formula (I) has the structure of formula (xv), wherein the TM part is the structure of formula (II) above (see formula (II) and its embodiments) or a pharmaceutically acceptable salt thereof.

[0482]

[0483] In one implementation, L can be covalently linked to any suitable site of formula (II).

[0484] The structure described in formula (III) falls within the scope of the structure described in formula (II). In one embodiment, the TM portion has the structure described in formula (III).

[0485]

[0486] Where R 42 R 43 R 44 R 45 R 46 R 47 R 48 R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 Each is independently selected from H, halogens, -NO2, -CN, =O, =S, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 Cyclic hydrocarbon group), -O (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (-(tri- to seven-membered heterocyclic groups), -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 alkyl), -N(C) 1-6 alkyl)-(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cyclic hydrocarbon group), -N(C) 1-6 alkyl)-(C=O)(C 3-6 cyclic hydrocarbon group), -NH(C=O)(C 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-6 alkyl)-(C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -NH (C=O) (three- to seven-membered heterocyclic groups), -N (C 1-6 Alkyl)-(C=O) (three to seven-membered heterocyclic groups), -COOH, -C(=O) (C 1-6 Alkyl), -C(=O)O(C 1-6 Alkyl), -C(=O)O(C 3-6 cyclic hydrocarbon group), -C(=O)O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -C(=O)O (three- to seven-membered heterocyclic groups), -C(=O)O (C 1-4 Alkylene group (ternary to seven-membered heterocyclic group), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-C(=O)NH(C 1-4Alkylene-C 3-6 cyclic hydrocarbon group), -C(=O)N(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -C(=O)NH (three- to seven-membered heterocyclic group), -C(=O)N (three- to seven-membered heterocyclic group)2, -C(=O)NH (C 1-4 alkylene-tertiary to seven-membered heterocyclic groups), -C(=O)N(C 1-4 alkylene-tertiary to heptaneous groups) 2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl), -S(=O)N(C 1-6 Alkyl)2, wherein the alkyl, alkylene, alkenyl, alkynyl, cycloalkyl or heterocyclic group is optionally selected from one or more halogens, nitro, cyano, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Substitution of alkyl group 2; or

[0487] Selected from R 42 R 43 R 44 R 45 R 46 R 47 R 48 R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 Two adjacent groups are linked together, forming a carbon atom along with the atoms they are attached to. 3-10 Hydrocarbon ring or three- to seven-membered heterocycle, wherein the hydrocarbon ring or heterocycle is optionally surrounded by one or more elements selected from halogen, nitro, cyano, -OH, -O(C) 1-6 Alkyl), -SH, -S(C1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2 substituents.

[0488] In one implementation scheme, R 42 R 43 R 44 R 45 R 46 R 47 R 48 R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 Each is independently selected from H, halogen, C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cycloalkyl), -O(C 1-4 Alkylene-C 3-6 cycloalkyl), -O (ternary to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 cycloalkyl), -O (C=O) (C 1-4 Alkylene-C 3-6 cycloalkyl), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cycloalkyl), -S(C 1-4 Alkylene-C 3-6cycloalkyl), -S (ternary to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cycloalkyl), -N(C) 3-6 cycloalkyl)2, -NH(C 1-4 Alkylene-C 3-6 cycloalkyl), -N(C) 1-4 Alkylene-C 3-6 cycloalkyl)2, -NH (tri- to seven-membered heterocyclic groups), -N (tri- to seven-membered heterocyclic groups)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cycloalkyl), -NH(C=O)(C 1-4 Alkylene-C 3-6 Cycloalkyl), -NH(C=O) (three to seven-membered heterocyclic groups), wherein the alkyl, alkylene, cycloalkyl or heterocyclic group is optionally replaced by one or more groups selected from halogen, nitro, cyano, -OH, -O(C=O) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Substitution of alkyl group 2; or

[0489] Selected from R 42 R 43 R 44 R 45 R 46 R 47 R 48 R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R57 Two adjacent groups are linked together, forming a carbon atom along with the atoms they are attached to. 3-10 Hydrocarbon ring or three- to seven-membered heterocycle, wherein the hydrocarbon ring or heterocycle is optionally surrounded by one or more elements selected from halogen, nitro, cyano, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2 substituents.

[0490] In another implementation, R 42 R 43 R 44 R 45 R 46 R 47 and R 48 Each is independently selected from H, halogens, -NO2, -CN, =O, =S, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 Cyclic hydrocarbon group), -O (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 alkyl), -N(C) 1-6 alkyl)-(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cyclic hydrocarbon group), -NH (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -NH(C=O) (three- to seven-membered heterocyclic groups), -C(=O) (C 1-6 Alkyl), -C(=O)O(C 1-6 Alkyl), -C(=O)O(C 3-6 cyclic hydrocarbon group), -C(=O)O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -C(=O)O (three- to seven-membered heterocyclic groups), -C(=O)O (C 1-4 alkylene)-(ternary to seven-membered heterocyclic groups), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-C(=O)NH(C 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -C(=O)N(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -C(=O)NH (three- to seven-membered heterocyclic group), -C(=O)N (three- to seven-membered heterocyclic group)2, -C(=O)NH (C 1-4 alkylene-tertiary to seven-membered heterocyclic groups), -C(=O)N(C 1-4 alkylene-tertiary to heptaneous groups) 2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl), -S(=O)N(C 1-6 Alkyl)2, wherein the alkyl, alkylene, alkenyl, alkynyl, cycloalkyl or heterocyclic group is optionally selected from one or more halogens, nitro, cyano, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Substituents of alkyl group 2; or selected from R 42 R 43 R 44 R 45 R 46 R 47 and R 48 Preferably selected from R 44 and R 45 Two adjacent groups are linked together, forming a carbon atom along with the atoms they are attached to. 3-10 Hydrocarbon ring or three- to seven-membered heterocycle, wherein the hydrocarbon ring or heterocycle is optionally surrounded by one or more elements selected from halogen, nitro, cyano, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2 substituents.

[0491] In yet another implementation scheme, R 42 R 43 R 44 R 45 R 46 R 47 and R48 Each is independently selected from H, halogen, C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cycloalkyl), -O(C 1-4 Alkylene-C 3-6 cycloalkyl), -O (ternary to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 cycloalkyl), -O (C=O) (C 1-4 Alkylene-C 3-6 cycloalkyl), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cycloalkyl), -S(C 1-4 Alkylene-C 3-6 cycloalkyl), -S (ternary to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cycloalkyl), -N(C) 3-6 cycloalkyl)2, -NH(C 1-4 Alkylene-C 3-6 cycloalkyl), -N(C) 1-4 Alkylene-C 3-6 cycloalkyl)2, -NH (tri- to seven-membered heterocyclic groups), -N (tri- to seven-membered heterocyclic groups)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cycloalkyl), -NH(C=O)(C 1-4 Alkylene-C 3-6 Cycloalkyl), -NH(C=O) (three to seven-membered heterocyclic groups), wherein the alkyl, alkylene, cycloalkyl or heterocyclic group is optionally replaced by one or more groups selected from halogen, nitro, cyano, -OH, -O(C=O) 1-6Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Substitution of alkyl group 2; or

[0492] Selected from R 42 R 43 R 44 R 45 R 46 R 47 and R 48 Preferably selected from R 44 and R 45 Two adjacent groups are linked together, forming a carbon atom along with the atoms they are attached to. 3-10 Hydrocarbon ring or three- to seven-membered heterocycle, wherein the hydrocarbon ring or heterocycle is optionally surrounded by one or more elements selected from halogen, nitro, cyano, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2 substituents.

[0493] In one implementation scheme, R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 Each is independently selected from H, halogen, C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl groups, wherein the alkyl cycloalkyl or heterocyclic group is optionally composed of one or more groups selected from halogen, nitro, cyano, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2 substituents.

[0494] In a specific implementation plan, R 42 R 43 R 44 R 45 R 46 R 47 and R 48 Each is independently selected from H, halogens, -NO2, -CN, =O, =S, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-NH(C=O)(C 1-6 alkyl), -N(C) 1-6 alkyl)-(C=O)(C 1-6 Alkyl group, -COOH group, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl), -S(=O)N(C 1-6 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C)1-6 alkyl), -N(C) 1-6 Alkyl)2 substituent; or, selected from R 42 R 43 R 44 R 45 R 46 R 47 and R 48 Preferably selected from R 44 and R 45 Two adjacent groups are linked together, forming a carbon atom along with the atoms they are attached to. 3-10 Hydrocarbon ring or three- to seven-membered heterocycle, wherein the hydrocarbon ring or heterocycle is optionally surrounded by one or more elements selected from halogens, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution with alkyl groups ()2, -COOH, -S(=O)2OH; and R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 Each is independently selected from H, halogen, C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl groups, wherein the alkyl, cycloalkyl, or heterocyclic group is optionally composed of one or more groups selected from halogens, -OH, -O(C) groups. 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution with alkyl groups (-2), -COOH, or -S(=O)2OH.

[0495] In yet another specific implementation plan, R 42 R 43 R 44 R 45 R 46 R 47 and R 48 At least one of them is -Cl, -Br, -I, -NO2, -CN, =O, =S, -OH, -O(C 1-6 Alkyl), -SH, -S(C1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-NH(C=O)(C 1-6 alkyl), -N(C) 1-6 alkyl)-(C=O)(C 1-6 Alkyl group, -COOH group, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl) or -S(=O)N(C 1-6 Alkyl group 2, the remaining groups are each independently selected from H, halogen, -NO2, -CN, =O, =S, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-NH(C=O)(C 1-6 alkyl), -N(C) 1-6 alkyl)-(C=O)(C 1-6 Alkyl group, -COOH group, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2-S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl), -S(=O)N(C 1-6 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution with alkyl groups (-2), -COOH, or -S(=O)2OH; or, selected from R 42 R 43 R 44 R 45 R46 R 47 and R 48 Preferably selected from R 44 and R 45 Two adjacent groups are linked together, forming a carbon atom along with the atoms they are attached to. 3-10 Hydrocarbon ring or three- to seven-membered heterocycle, wherein the hydrocarbon ring or heterocycle is optionally surrounded by one or more elements selected from halogens, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution with alkyl groups (-2), -COOH, or -S(=O)2OH.

[0496] In one particular implementation scheme, R 42 R 43 R 44 R 45 R 46 R 47 and R 48 At least one of them is -Cl, -Br, -I, -OH, -O(C 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl) or -N(C) 1-6 Alkyl group 2, preferably -OH, -SH or -NH2, more preferably -OH or -NH2, particularly preferably -OH, the remaining groups are each independently selected from H, halogen, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2; wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O (C 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution with alkyl groups (-2), -COOH, or -S(=O)2OH; or, selected from R 42 R 43 R 44 R 45 R 46 R 47 and R 48 Preferably selected from R 44 and R 45Two adjacent groups are linked together, forming a carbon atom along with the atoms they are attached to. 3-10 Hydrocarbon ring or three- to seven-membered heterocycle, wherein the hydrocarbon ring or heterocycle is optionally surrounded by one or more elements selected from halogens, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution with alkyl groups (-2), -COOH, or -S(=O)2OH.

[0497] In another specific implementation scheme, R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 For H, or R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 At least one of them, preferably 1-6, more preferably 1-4, and particularly preferably 1, 2, or 4 are C. 1-6 Alkyl or -O(C) 1-6 Alkyl), preferably C 1-3 Alkyl or -O(C) 1-3 Alkyl), wherein C 1-3 Alkyl groups are particularly preferred to be methyl groups, -O(C 1-3 Alkyl groups are particularly preferred, with methoxy groups being selected independently from H, halogens, C, and so on. 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl groups, preferably selected from H and halogens, particularly preferably H; wherein the alkyl group is optionally surrounded by one or more elements selected from halogens, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2 substituents.

[0498] In yet another specific implementation plan, R 42 R 43R 44 R 45 R 46 R 47 and R 48 At least one of them is -Cl, -Br, -I, -NO2, -CN, =O, =S, -OH, -O(C 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-NH(C=O)(C 1-6 alkyl), -N(C) 1-6 alkyl)-(C=O)(C 1-6 Alkyl group, -COOH group, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl) or -S(=O)N(C 1-6 Alkyl group 2, the remaining groups are each independently selected from H, halogen, -NO2, -CN, =O, =S, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-NH(C=O)(C 1-6 alkyl), -N(C) 1-6 alkyl)-(C=O)(C 1-6 Alkyl group, -COOH group, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2-S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl), -S(=O)N(C 1-6 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution with alkyl groups (-2), -COOH, or -S(=O)2OH; or, selected from R 42 R 43 R 44 R 45 R 46 R 47 and R 48 Preferably selected from R 44 and R 45 Two adjacent groups are linked together, forming a carbon atom along with the atoms they are attached to. 3-10 Hydrocarbon ring or three- to seven-membered heterocycle, wherein the hydrocarbon ring or heterocycle is optionally surrounded by one or more elements selected from halogens, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution with alkyl groups ()2, -COOH, -S(=O)2OH; and R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 For H, or R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 At least one of them, preferably 1-6, more preferably 1-4, and particularly preferably 1, 2, or 4 are C. 1-6 Alkyl or -O(C) 1-6 Alkyl), preferably C 1-3 Alkyl or -O(C) 1-3 Alkyl), wherein C 1-3 Alkyl groups are particularly preferred to be methyl groups, -O(C 1-3 Alkyl groups are particularly preferred, with methoxy groups being selected independently from H, halogens, C, and so on. 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4Alkyl groups, preferably selected from H and halogens, particularly preferably H; wherein the alkyl group is optionally surrounded by one or more elements selected from halogens, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution of alkyl group 2;

[0499] In yet another specific implementation plan, R 49 and R 52 At least one of them is C 1-6 Alkyl or -O(C) 1-6 Alkyl), preferably C 1-3 Alkyl or -O(C) 1-3 Alkyl), wherein C 1-3 Alkyl groups are particularly preferred to be methyl groups, -O(C 1-3 Alkyl groups, particularly methoxy groups, and / or R groups are preferred. 50 and R 51 At least one of them is C 1-6 Alkyl or -O(C) 1-6 Alkyl), preferably C 1-3 Alkyl or -O(C) 1-3 Alkyl), wherein C 1-3 Alkyl groups are particularly preferred to be methyl groups, -O(C 1-3 Alkyl groups, particularly methoxy groups, and / or R groups are preferred. 53 and R 56 At least one of them is C 1-6 Alkyl or -O(C) 1-6 Alkyl), preferably C 1-3 Alkyl or -O(C) 1-3 Alkyl), wherein C 1-3 Alkyl groups are particularly preferred to be methyl groups, -O(C 1-3 Alkyl groups, particularly methoxy groups, and / or R groups are preferred. 54 and R 57 At least one of them is C 1-6 Alkyl or -O(C) 1-6 Alkyl), preferably C 1-3 Alkyl or -O(C) 1-3 Alkyl), wherein C 1-3 Alkyl groups are particularly preferred to be methyl groups, -O(C 1-3 Alkyl) particularly preferred methoxy, R 42 R 43 R 44 R 45 R 46 R 47 R 48 R 49 R 50 R51 R 52 R 53 R 54 R 55 R 56 and R 57 The remaining groups are each independently selected from H, halogens, C. 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl groups, preferably selected from H and halogens, particularly preferably H; wherein the alkyl group is optionally surrounded by one or more elements selected from halogens, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2 substituents.

[0500] In one particular implementation scheme, R 42 R 43 R 44 R 45 R 46 R 47 and R 48 One of them is -OH, -SH or -NH2, more preferably -OH or -NH2, particularly preferably -OH, and the remaining groups are H; R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 For H, or R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 At least one of them, preferably 1-6, more preferably 2-4, and particularly preferably 2 or 4 are C 1-3 Alkyl, preferably C 1-3 Alkyl groups, more preferably methyl groups, and the remaining groups are each independently selected from H or R. 49 R 50 R 51 R 52 R 53 R 54R 55 R 56 and R 57 At least one of them, preferably 1-6, more preferably 1-4, and particularly preferably 1 or 2 are -O(C 1-6 Alkyl), preferably -O(C) 1-3 Alkyl groups, more preferably methoxy groups, and the remaining groups are each independently selected from H.

[0501] In another particular implementation, R 42 It is -OH, -SH or -NH2, more preferably -OH or -NH2, particularly preferably -OH, R 43 R 44 R 45 R 46 R 47 and R 48 Each is independently selected from H, -OH, -SH or -NH2, more preferably H, -OH or -NH2, particularly preferably H or -OH, especially H; R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 For H, or R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 At least one of them, preferably 1-6, more preferably 2-4, and particularly preferably 2 or 4 are C 1-3 Alkyl, preferably C 1-3 Alkyl groups, more preferably methyl groups, and the remaining groups are each independently selected from H or R. 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 At least one of them, preferably 1-6, more preferably 1-4, and particularly preferably 1 or 2 are -O(C 1-6 Alkyl), preferably -O(C) 1-3 Alkyl groups, more preferably methoxy groups, and the remaining groups are each independently selected from H.

[0502] In yet another specific implementation, the structure of formula (III) is selected from:

[0503]

[0504] Preferably selected from in particular

[0505] Therefore, in one embodiment, formula (I) has the structure of formula (xvi), wherein the TM part is the structure of formula (III) above (see formula (III) and its embodiments) or a pharmaceutically acceptable salt thereof.

[0506]

[0507] In one implementation, L can be covalently linked to any suitable site of formula (III).

[0508] In a particular implementation, the structure of formula (xvi) is selected from:

[0509]

[0510] Preferably selected from in particular

[0511] The structure described in formula (IV) falls within the scope of the structure described in formula (II). In one embodiment, the TM portion has the structure described in formula (IV).

[0512]

[0513] Where R 42 R 43 R 44 R 45 R 46 R 47 R 48 R 53 R 54 R 55 R 56 and R 57 As defined in equation (III).

[0514] In a particular embodiment, the structure of formula (IV) is selected from:

[0515]

[0516] Therefore, in one embodiment, formula (I) has the structure of formula (xvii), wherein the TM part is the structure of formula (IV) above (see formula (IV) and its embodiments) or a pharmaceutically acceptable salt thereof.

[0517]

[0518] In one implementation, L can be covalently linked to any suitable site of formula (IV).

[0519] In a particular implementation, the structure of formula (xvii) is selected from:

[0520]

[0521] The structure described in formula (V) falls within the scope of the structure described in formula (II). In one embodiment, the TM portion has the structure described in formula (V).

[0522]

[0523] Where R 42 R 43 R 44 R 45 R 46 R 47 R 48 R 53 R 54 R 55 R 56 and R 57 As defined in equation (III);

[0524] Where R 58 R 59 R 60 R 61 R 62 and R 63 Each is independently selected from H, halogens, -NO2, -CN, =O, =S, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 Cyclic hydrocarbon group), -O (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (-(tri- to seven-membered heterocyclic groups), -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 alkyl), -N(C) 1-6 alkyl)-(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cyclic hydrocarbon group), -N(C) 1-6 alkyl)-(C=O)(C 3-6 cyclic hydrocarbon group), -NH (C=O)(C 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-6 alkyl)-(C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -NH (C=O) (three- to seven-membered heterocyclic groups), -N (C 1-6 Alkyl)-(C=O) (three to seven-membered heterocyclic groups), -COOH, -C(=O) (C 1-6 Alkyl), -C(=O)O(C 1-6 Alkyl), -C(=O)O(C 3-6 cyclic hydrocarbon group), -C(=O)O(C 1-4 Alkylene-C3-6 Cyclic hydrocarbon groups), -C(=O)O (three- to seven-membered heterocyclic groups), -C(=O)O (C 1-4 Alkylene group (ternary to seven-membered heterocyclic group), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-C(=O)NH(C 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -C(=O)N(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -C(=O)NH (three- to seven-membered heterocyclic group), -C(=O)N (three- to seven-membered heterocyclic group)2, -C(=O)NH (C 1-4 alkylene-tertiary to seven-membered heterocyclic groups), -C(=O)N(C 1-4 alkylene-tertiary to heptaneous groups) 2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl), -S(=O)N(C 1-6 Alkyl)2, wherein the alkyl, alkylene, alkenyl, alkynyl, cycloalkyl or heterocyclic group is optionally selected from one or more halogens, nitro, cyano, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2 substituents.

[0525] In a specific implementation plan, R 58 R 59 R 60 R 61 R 62 and R 63 For H, or R 58 R 59 R 60 R 61 R 62 and R 63At least one of them, preferably 1-6, more preferably 1-4, and particularly preferably 1, 2, or 4 are C. 1-6 Alkyl or -O(C) 1-6 Alkyl), preferably C 1-3 Alkyl or -O(C) 1-3 Alkyl), wherein C 1-3 Alkyl groups are particularly preferred to be methyl groups, -O(C 1-3 Alkyl groups are particularly preferred, with methoxy groups being selected independently from H, halogens, C, and so on. 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl groups, preferably selected from H and halogens, particularly preferably H; wherein the alkyl group is optionally surrounded by one or more elements selected from halogens, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 The alkyl group is substituted. In a particular embodiment, R... 58 R 59 R 60 R 61 R 62 and R 63 For H.

[0526] In a particular implementation, the structure of formula (V) is as follows:

[0527]

[0528] Therefore, in one embodiment, formula (I) has the structure of formula (xviii), wherein the TM part is the structure of formula (V) above (see formula (V) and its embodiments above) or a pharmaceutically acceptable salt thereof.

[0529]

[0530] In one implementation, L can be covalently linked to any suitable site of formula (V).

[0531] In a particular implementation, the structure of equation (xviii) is as follows:

[0532]

[0533] The structure described in formula (VI) falls within the scope of the structure described in formula (II). In one embodiment, the TM portion has the structure described in formula (VI).

[0534]

[0535] Where R 42 R 43 R 44 R 45 R 46 R 47 R 48 R 53 R 54 R 55 R 56 and R 57 As defined in equation (III).

[0536] In another particular implementation, the structure of formula (VI) is as follows:

[0537]

[0538] Therefore, in one embodiment, formula (I) has the structure of formula (xix), wherein the TM part is the structure of formula (VI) above (see formula (VI) and its embodiments above) or a pharmaceutically acceptable salt thereof.

[0539]

[0540] In one implementation, L can be covalently linked to any suitable site of formula (VI).

[0541] In another specific implementation, the structure of formula (xix) is as follows:

[0542]

[0543] In an alternative embodiment, two or more structures of formula (II) are interconnected to form a conjugate or hybrid, a structure also included in the concept of the compound TM portion of the present invention. In a particular embodiment, the compound TM portion of the present invention is:

[0544]

[0545] Therefore, in one embodiment, formula (I) has the following structure

[0546]

[0547] In one implementation, L can be covalently linked to any suitable site of formula (II).

[0548] In one embodiment, the TM portion has the structure of the following formula (VII):

[0549]

[0550] in, Indicates a single bond or a double bond;

[0551] when When representing a double bond, R a Does not exist; when When representing a single bond, R a Selected from H, OH, -O(C) 1-8 alkyl), -O(C) 1-8 silyl), -C(=O)O(C 1-26 Alkyl), -C(=O)O(C 1-26 (alkenyl), wherein the alkenyl group contains 1-8 double bonds;

[0552] R b R c R d Each is independently selected from H and C. 1-8 Alkyl, C 1-8 alkenyl, -OH, -O(C) 1-8 alkyl), -O(C) 1-8 Silyl);

[0553] R e R f R g Each is independently selected from H and C. 1-4 Alkyl, -OH, -O(C) 1-4 alkyl);

[0554] L 7 Selected from chemical bonds, C 1-8 Alkylene;

[0555] R h Selected from H, C 1-20 Alkyl, C 1-20 alkenyl, -OH, -O(C) 1-20 alkyl), -O(C) 1-20 Silyl group), wherein the alkyl and alkenyl groups are optionally selected from one or more groups selected from -OH, C 1-8 Alkyl, C 1-8 alkenyl, C 1-8 alkynyl group, -O(C) 1-20 alkyl), -O(C) 1-20 Substitution of silyl groups;

[0556] k can be 0, 1, or 2.

[0557] In one implementation scheme, Indicates a single bond, R a Selected from H, OH, -O(C) 1-8Alkyl), -C(=O)O(C 1-22 Alkyl), -C(=O)O(C 1-22 Alkenyl), wherein the alkenyl group contains 1-8, preferably 2-6, and more preferably 3-6 double bonds.

[0558] In one implementation scheme, R b R c R d For H. In another implementation, R e R f It is methyl. In yet another embodiment, R g It is methyl. In yet another embodiment, R h C 3-10 Alkyl, preferably C 5-8 Alkyl, more preferably C 6-7 Alkyl groups, especially C6 alkyl groups.

[0559] In a particular implementation, the structure of formula (VII) is selected from:

[0560]

[0561] Therefore, in one embodiment, formula (I) has the structure of formula (xx) below, wherein the TM part is the structure of formula (VII) above (see formula (VII) and its embodiments above) or a pharmaceutically acceptable salt thereof.

[0562]

[0563] In one implementation, L can be covalently linked to any suitable site of formula (VII).

[0564] In a particular implementation, the structure of formula (xx) is selected from:

[0565]

[0566] In one embodiment, the TM portion comprises an alkynyl or azide group. In a particular embodiment, the TM portion is... Or -N3.

[0567] Therefore, in one embodiment, equation (I) has the structure of equation (xxi) or equation (xxii), wherein the TM part is or -N3

[0568]

[0569] LCM-L-N3(xxii)

[0570] Coupling compounds

[0571] Some examples of coupling compounds are described by formulas (i) to (xxii).

[0572] The LCM moiety is covalently linked to L, and the TM moiety is covalently linked to L, wherein the covalent linking site can be any suitable site. In one embodiment, the carbon atom of the LCM moiety is covalently linked to L. In another embodiment, the heteroatom of the LCM moiety is covalently linked to L. Those skilled in the art can select a suitable reaction for linking based on the structure of the LCM, L, and TM moiety, and conversely, can adjust the substituents of the LCM, L, and TM moiety according to the type of reaction. It should be understood that when the LCM moiety is covalently linked to L, and the TM moiety is covalently linked to L, the structure of the product (coupling compound) can be easily determined based on the structure of the LCM, L, and TM moiety before covalent linking; conversely, the structure of the LCM, L, and TM moiety before covalent linking can be easily determined based on the structure of the product (coupling compound). In a particular embodiment, both the LCM moiety and L contain hydroxyl groups, and the hydroxyl group of the LCM moiety and the hydroxyl group of L form a covalent link and lose one molecule of water. In another particular embodiment, both the TM moiety and L contain hydroxyl groups, and the hydroxyl groups of the TM moiety and L are covalently linked, with one molecule of water being removed. In another particular embodiment, L contains a nucleophilic reactive site, and the LCM moiety contains an O- or N-containing structure with nucleophilic reactivity, which is covalently linked to the nucleophilic reactive site in L. In another particular embodiment, L contains a nucleophilic reactive site, and the TM moiety contains an O- or N-containing structure with nucleophilic reactivity, which is covalently linked to the nucleophilic reactive site in L.

[0573] In one embodiment, the compound of formula (I) is selected from the following:

[0574]

[0575]

[0576]

[0577] In one embodiment, the compound of formula (I) is selected from compounds 1A, 1B, 2A, 2B, 3A, 3B, 4A, 4B, 5A, 6, 7, 8, 9, 10A, 10B, and 11A, preferably selected from compounds 1A, 1B, 2A, 2B, 3A, 3B, 4A, 4B, 5A, 6, 7, 8, 9, 10A, and 11A. In another embodiment, the compound of formula (I) is selected from compounds 1A, 1B, 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 6, 7, 8, and 9.

[0578] Preparation methods of compounds

[0579] In another aspect, the present invention provides a method for preparing the compounds of the present invention, comprising: covalently linking a structure capable of binding LC3 protein with a structure capable of binding lipid droplets, thereby forming an "LC3-binding moiety-lipid-droplet-binding moiety conjugate" ("conjugate compound"). The portions of the conjugate compound are as described above.

[0580] In one implementation, structures capable of binding the LC3 protein are screened or identified using the following methods:

[0581] (I): Contacting the candidate compound with a test system containing LC3 protein or its homologs or fragments thereof; and

[0582] (II): Select compounds that bind with affinity to LC3 protein or its homologs or fragments thereof.

[0583] In one implementation, structures capable of binding lipid droplets are screened or identified using the following methods:

[0584] (I'): Contact the candidate compound with the test system, the test system containing a target, the target being a lipid droplet or a lipid droplet-labeled protein or a neutral lipid known to be present in the target lipid droplet; and

[0585] (II'): Select compounds that bind non-covalently to the target described in (I').

[0586] Pharmaceutical compositions and pharmaceutical preparations

[0587] Another object of the present invention is to provide a pharmaceutical composition comprising a preventive or therapeutically effective amount of the compound of the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite or prodrug, and one or more pharmaceutically acceptable carriers.

[0588] In this invention, "pharmaceutically acceptable carrier" refers to a diluent, excipient, vehicle, or medium that is administered co-administered with a therapeutic agent and is suitable, to the extent of reasonable medical judgment, for contact with human and / or other animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications commensurate with a reasonable benefit / risk ratio.

[0589] In one embodiment, the present invention provides a capsule containing the compound of the present invention but without an additional carrier.

[0590] The pharmaceutical compositions of the present invention may be in the form of tablets, chewable tablets, capsules, solutions, parenteral solutions, lozenges, suppositories, and suspensions. The compositions may be formulated to contain a suitable portion of a daily dose in a dosage unit, which may be a single tablet or capsule or a suitable volume of liquid.

[0591] In one embodiment, the solution is prepared from a water-soluble salt, such as hydrochloride. Typically, all compositions are prepared according to methods known in medicinal chemistry. Capsules can be prepared by mixing the compound with a suitable carrier or diluent and filling an appropriate amount of the mixture into a capsule. Commonly used carriers and diluents include, but are not limited to, inert powdered substances such as various starches, powdered cellulose, especially crystalline and microcrystalline cellulose, sugars such as fructose, mannitol and sucrose, cereal flours and similar edible powders.

[0592] Tablets can be prepared by direct compression, wet granulation, or dry granulation. Their formulation typically includes diluents, binders, lubricants, disintegrants, and the compound itself. Typical diluents include, for example, various types of starch, lactose, mannitol, kaolin, calcium phosphate or calcium sulfate, inorganic salts (such as sodium chloride), and powdered sugar. Powdered cellulose derivatives are also useful. Typical tablet binders include substances such as starch, gelatin, and sugars (such as lactose, fructose, glucose, etc.). Natural and synthetic gums are also suitable, including gum arabic, alginate, methylcellulose, polyvinylpyrrolidone, etc. Polyethylene glycol, ethylcellulose, and waxes can also act as binders.

[0593] Lubricants can be selected from slippery solids such as talc, magnesium stearate and calcium stearate, stearic acid, and hydrogenated vegetable oils. Tablet disintegrants swell upon wetting to break up the tablet and release a compound. These include starch, clay, cellulose, alginate, and gums. More specifically, corn and potato starch, methylcellulose, agar, bentonite, wood cellulose, powdered natural sponges, anion exchange resins, alginate, guar gum, citrus pomace, and carboxymethyl cellulose, as well as sodium lauryl sulfate, can be used. Tablets can be coated with sugars as flavoring and sealing agents, or with film-forming protectants to optimize tablet solubility. The composition can also be formulated into chewable tablets, for example, by adding substances such as mannitol to the formulation.

[0594] When administration as a suppository is desired, typical bases can be used. Cocoa butter is a traditional suppository base, which can be altered by adding wax to slightly increase its melting point. Water-miscible suppository bases, particularly those comprising polyethylene glycol of various molecular weights, are widely used.

[0595] The action of the compound can be delayed or prolonged by appropriate formulation. For example, slow-dissolving pellets of the compound can be prepared and incorporated into tablets or capsules or used as sustained-release implantable devices. The technique also includes preparing pellets with several different dissolution rates and filling capsules with a mixture of pellets. Tablets or capsules can be coated with a film that resists dissolution for a predictable period. Even parenteral formulations can be prepared to have a long-lasting effect by dissolving or suspending the compound in an oily or emulsified solvent that allows it to disperse slowly in serum.

[0596] In one embodiment, the pharmaceutical composition and / or pharmaceutical formulation of the present invention are provided in the form of a kit.

[0597] Treatment methods and uses

[0598] In one aspect, the present invention provides a method for reducing intracellular lipid droplets, comprising contacting the coupling compound of the present invention with cells or tissues containing lipid droplets, wherein the lipid droplets are contained in the cells under physiological or pathological conditions, and / or are induced to be generated by the cells.

[0599] Cells or tissues containing lipid droplets can be derived, for example, from normal cells or tissues, biological models associated with lipid droplet accumulation, or cells or tissues from clinical patients. In one embodiment, the lipid droplets are those contained in cells under normal physiological conditions. In another embodiment, the lipid droplets are those contained in cells under pathological conditions related to lipid metabolism disorders. In yet another embodiment, the lipid droplets are those induced in cells by exogenous substances (e.g., sodium oleate).

[0600] In one aspect, the present invention provides the use of the compounds of the present invention or pharmaceutically acceptable salts, stereoisomers, solvates, polymorphs, tautomers, isotopic compounds, metabolites or prodrugs thereof, or pharmaceutical compositions of the present invention, in the preparation of a medicament for reducing intracellular lipid droplets.

[0601] In another aspect, the present invention provides compounds of the present invention or pharmaceutically acceptable salts, stereoisomers, solvates, polymorphs, tautomers, isotopic compounds, metabolites or prodrugs thereof, or pharmaceutical compositions of the present invention, for reducing intracellular lipid droplets.

[0602] In a further aspect, the present invention provides a method for reducing intracellular lipid droplets, the method comprising administering to an individual in need an effective amount of a compound of the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite or prodrug, or a pharmaceutical composition of the present invention.

[0603] In one aspect, the present invention provides the use of the compounds of the present invention or pharmaceutically acceptable salts, stereoisomers, solvates, polymorphs, tautomers, isotopic compounds, metabolites or prodrugs thereof, or pharmaceutical compositions of the present invention, in the preparation of medicaments for the treatment or prevention of lipid metabolism-related diseases.

[0604] In another aspect, the present invention provides compounds of the present invention or pharmaceutically acceptable salts, stereoisomers, solvates, polymorphs, tautomers, isotopic compounds, metabolites or prodrugs thereof, or pharmaceutical compositions of the present invention, for the treatment or prevention of lipid metabolism-related diseases.

[0605] In a further aspect, the present invention provides a method for preventing or treating lipid metabolism-related diseases, the method comprising administering to an individual in need an effective amount of a compound of the present invention or a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite or prodrug, or a pharmaceutical composition of the present invention.

[0606] The compounds of the present invention can be administered orally or parenterally to patients in conventional formulations, such as capsules, microcapsules, tablets, granules, powders, lozenges, pills, suppositories, injections, suspensions, syrups, patches, creams, lotions, ointments, gels, sprays, solutions, and emulsions. Suitable formulations can be prepared using conventional organic or inorganic additives by commonly employed methods, such as excipients (e.g., sucrose, starch, mannitol, sorbitol, lactose, glucose, cellulose, talc, calcium phosphate, or calcium carbonate), binders (e.g., cellulose, methylcellulose, hydroxymethylcellulose, polypropylene pyrrolidone, polyvinylpyrrolidone, gelatin, gum arabic, polyethylene glycol, sucrose, or starch), and disintegrants (e.g., starch, carboxymethylcellulose, hydroxypropyl starch, low-substituted hydroxypropylcellulose, sodium bicarbonate). The ingredients include calcium phosphate or calcium citrate, lubricants (e.g., magnesium stearate, light anhydrous silicate, talc or sodium lauryl sulfate), flavoring agents (e.g., citric acid, menthol, glycine or orange powder), preservatives (e.g., sodium benzoate, sodium bisulfite, methylparaben or propylparaben), stabilizers (e.g., citric acid, sodium citrate or acetic acid), suspending agents (e.g., methylcellulose, polyvinylpyrrolidone or aluminum stearate), dispersants (e.g., hydroxypropyl methylcellulose), diluents (e.g., water) and base waxes (e.g., cocoa butter, white petrolatum or polyethylene glycol).

[0607] Dosing regimens can be adjusted to provide the optimal required response. For example, when administered in injectable form, a single bolus, bolus, and / or continuous infusion can be given, etc. For example, several fractions can be administered over time, or the dose can be reduced or increased proportionally as indicated by the urgency of the treatment situation. It should be noted that dosage values ​​can vary depending on the type and severity of the condition to be alleviated, and can include single or multiple doses. Generally, the dosage of treatment is variable, depending on considerations such as: the age, sex, and general health of the patient to be treated; the frequency of treatment and the nature of the desired effect; the extent of tissue damage; the duration of symptoms; and other variables that can be adjusted by individual physicians. To further understand, for any particular individual, the specific dosing regimen should be adjusted over time based on individual needs and the professional judgment of the person administering the composition or supervising the administration of the composition. The dosage and administration regimen of the pharmaceutical composition can be readily determined by a person skilled in the clinical field. For example, the compositions or compounds of the present invention can be administered in fractions from four times daily to once every three days, with dosages ranging from, for example, 0.01 to 1000 mg per dose. The required dose can be administered once or multiple times to achieve the desired result. The pharmaceutical composition according to the invention can also be provided in unit dose form.

[0608] combination therapy

[0609] This invention provides compounds of the invention or pharmaceutically acceptable salts, stereoisomers, solvates, polymorphs, tautomers, isotopic compounds, metabolites, or prodrugs thereof, or pharmaceutical compositions or formulations of the invention, which can be used in combination with other therapeutic agents for the treatment or prevention of lipid metabolism-related diseases. In one embodiment, the other therapeutic agents are selected from substances that treat or prevent insulin resistance, substances that lower free fatty acid levels, and substances that lower cholesterol levels.

[0610] Exemplary embodiments of the present invention may also be listed below:

[0611] <1> A compound or a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite, or prodrug thereof, said compound having a structure comprising formula (I).

[0612] LCM―L―TM(I)

[0613] in:

[0614] LCM is the LC3 bonding portion;

[0615] L represents the connector section;

[0616] TM represents the lipid droplet binding region.

[0617] <2> The above <1> The compound or its pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite or prodrug, wherein, in formula (I), the LCM portion is the portion having affinity for the LC3 protein, and the TM portion is the portion capable of non-covalently interacting with lipid droplets.

[0618] <3> The above <1> or <2> The compound or its pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite or prodrug, wherein formula (1) has the structure of formula (2) as follows:

[0619]

[0620] in:

[0621] Y is either O or S;

[0622] Ring C is selected from C 6-10 Aryl and five- to seven-membered heteroaryl groups, wherein the aryl or heteroaryl group is optionally selected from one or more independently selected from R X1 Substitution of groups;

[0623] R 2 Selected from H, C 1-8 alkyl;

[0624] L 1 It is a bond, or a C1-C6 hydrocarbon chain;

[0625] R 3 R 4 R 5 R 6 Each is independently selected from H and R X2 ;

[0626] Where R X1 R X2 As mentioned above <3> Defined in the document;

[0627] R X1 and R X2 Each time it appears, it is independently selected from halogen, -NO2, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, -OR 7 -SR 7 -NR 7 R 8 -C(=O)OR 7 -C(=O)NR 7 R 8 -OC(=O)R 7 -NC(=O)R7 R 8 -C(=O)R 7 -S(=O)2OR 7 -S(=O)2R 7 -S(=O)2NR 7 R 8 -OS(=O)2R 7 -NS(=O)2R 7 R 8 -S(=O)R 7 The alkyl, alkenyl, or alkynyl group is optionally selected from one or more halogens, -NO2, -CN, -OH, -O(C 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 alkylene (tri- to seven-membered heterocyclic groups) 2, =O, -COOH and C 1-6 Alkyl substituents;

[0628] R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl-C 1-4 Alkyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic or aryl group is optionally selected from one or more halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Substitution of alkyl groups;

[0629] R a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl, five- to ten-membered heteroaryl-C 1-4 Alkyl, -OR Y1 -SR Y1 -NR Y1 R Y2 -C(=O)OR Y1 -C(=O)NR Y1 R Y2 -C(=O)R Y1 -S(=O)2OR Y1 -S(=O)2R Y1 -S(=O)2NR Y1 R Y2 -S(=O)R Y1The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more halogens, =O, =S, -OR. Y3 -SR Y3 -NR Y3 R Y4 -C(=O)R Y3 -C(=O)OR Y3 and -C(=O)NR Y3 R Y4 Substituents of the substituents;

[0630] R Y1 R Y2 R Y3 R Y4 Each time it appears, it is independently selected from H and C. 1-8 Alkyl, C 3-10 Cyclic hydrocarbon group, C 3-10 Cyclic hydrocarbon group -C 1-4 Alkyl, ternary to ten-membered heterocyclic groups, ternary to ten-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl, five- to ten-membered heteroaryl-C 1-4 Alkyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally selected from one or more halogens, -NO2, -CN, C 1-8 Alkyl, C 2-8 alkenyl, C 2-8 Substitution of alkynyl, -OH, -SH, -NH2, =O and -COOH groups;

[0631] Specifically, the structure of equation (2) is selected from:

[0632]

[0633] <4> The above <1> or <2> The compound or its pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite or prodrug, wherein formula (1) has the structure of formula (5) as follows:

[0634]

[0635] in:

[0636] Y is either O or S;

[0637] R 9 Selected from H, halogens, C 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C 3-6Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OR a1 -SR a1 -NR a1 R b1 -C(=O)OR a1 -C(=O)NR a1 R b1 -C(=O)R a1 -S(=O)2OR a1 -S(=O)2R a1 -S(=O)2NR a1 R b1 -S(=O)R a1 The alkyl, cyclic, or heterocyclic group is optionally selected from one or more halogens, -NO2, -CN, C 1-6 Alkyl, -OR a2 -SR a2 -NR a2 R b2 -C(=O)OR a2 -C(=O)NR a2 R b2 -C(=O)R a2 -S(=O)2OR a2 -S(=O)2R a2 -S(=O)2NR a2 R b2 and -S(=O)R a2 Substituents of R; where R a1 R b1 R a2 R b2 As mentioned above <3> Defined in the document;

[0638] R 10 Selected from H, halogens, C 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 alkyl;

[0639] R 3 Selected from H, halogens, C 1-6 Alkyl, -OH, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-6Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution of alkyl group 2;

[0640] R 4 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, -OR 7 -SR 7 -NR 7 R 8 ;R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Alkyl) substituents; wherein R 7 R 8 As mentioned above <3> Defined in the document;

[0641] R 5 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Alkyl group), wherein the alkyl group is optionally composed of one or more elements selected from halogens, -OH, -O (C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(=O)O(C 1-6Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Substitution of alkyl groups;

[0642] R 6 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl), -O (benzyl), -SH, -S (C 1-6 Alkyl), -S (benzyl), -NH2, -NH (C 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -NH (benzyl), wherein the alkyl or benzyl group is optionally surrounded by one or more elements selected from halogen, -OH, -O (C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution of alkyl group 2;

[0643] Specifically, the structure of equation (5) is as follows:

[0644]

[0645] <5> The above <1> or <2> The compound or its pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite or prodrug, wherein the formula (6) has the structure of the following formula (8):

[0646]

[0647] in:

[0648] Y is either O or S;

[0649] C ring is Where R 14 R 15 R 16 R 17 R 18 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, -OR 7 -SR 7 -NR 7 R 8 -C(=O)OR 7-C(=O)NR 7 R 8 -OC(=O)R 7 -NC(=O)R 7 R 8 -C(=O)R 7 -S(=O)2OR 7 -S(=O)2R 7 -S(=O)2NR 7 R 8 -OS(=O)2R 7 -NS(=O)2R 7 R 8 -S(=O)R 7 ;where R 7 R 8 As mentioned above <6> As defined in [the document]; preferably, R 14 R 15 R 17 R 18 Each is independently selected from H, halogens, -NO2, -CN, and C. 1-6 Alkyl, -OH, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-NH(C=O)(C 1-6 alkyl), and R 16 It is H or -OCH3;

[0650] R 2 Selected from H, halogens, C 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl group, wherein the alkyl group, cycloalkyl group, or heterocyclic group is optionally composed of one or more elements selected from halogen, -NO2, -CN, C 1-6 Alkyl, -OR a2 -SR a2 -NR a2 R b2 -C(=O)OR a2 -C(=O)NR a2 R b2 -C(=O)R a2 -S(=O)2OR a2 -S(=O)2R a2 -S(=O)2NR a2 R b2 and -S(=O)R a2 Substituents of R; where R a2R b2 R c2 As mentioned above <6> As defined in [the document]; preferably, R 2 Selected from H, halogens, C 1-6 Alkyl group, wherein the alkyl group is optionally substituted with one or more substituents selected from halogen, -NO2, -CN, -OH, -NH2 and -COOH;

[0651] R 3 Selected from H, -OH, C 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, -OH, -SH, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 Substitution of alkylene-ter to seven-membered heterocyclic groups) and -COOH groups;

[0652] R 4 Selected from H, -OR 7 -SR 7 -NR 7 R 8 ;R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Substitution of alkyl group 2;

[0653] R 5 Selected from H, C 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, -OH, -O(C) 1-6alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 Substitution of alkylene-tertiary to seven-membered heterocyclic groups) and -COOH groups; and

[0654] R 6 Selected from H, halogens, C 1-6 Alkyl, -OH, -NH2, wherein the alkyl group is optionally substituted with one or more substituents selected from halogen, -OH, -NH2;

[0655] In particular, the structure of equation (8) is selected from:

[0656]

[0657] <6> The above <1> or <2> The compound or its pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite or prodrug, wherein the formula (6) has the structure of the following formula (9):

[0658]

[0659] in:

[0660] R 2 Selected from H, halogens, -NO2, -CN, C 1-6 Alkyl, C 3-6 Cyclic hydrocarbon group, C 3-6Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OR a1 -SR a1 -NR a1 R b1 -C(=O)OR a1 -C(=O)NR a1 R b1 -C(=O)R a1 -S(=O)2OR a1 -S(=O)2R a1 -S(=O)2NR a1 R b1 -S(=O)R a1 The alkyl, cyclic, or heterocyclic group is optionally selected from one or more halogens, -NO2, -CN, C 1-6 Alkyl, -OR a2 -SR a2 -NR a2 R b2 -C(=O)OR a2 -C(=O)NR a2 R b2 -C(=O)R a2 Substituents of the substituents;

[0661] R 19 Each time it appears, it is independently selected from halogen, -NO2, -CN, C. 1-6 Alkyl, -OR 7 -SR 7 -NR 7 R 8 -C(=O)OR 7 -C(=O)NR 7 R 8 -OC(=O)R 7 -NC(=O)R 7 R 8 -C(=O)R 7 -S(=O)2OR 7 -S(=O)2R 7 -S(=O)2NR 7 R 8 -OS(=O)2R 7 -NS(=O)2R 7 R 8 -S(=O)R 7 The alkyl group is optionally surrounded by one or more elements selected from halogens, -NO2, -CN, -OH, -O(C).1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution with alkyl groups (2) or -COOH;

[0662] m can be 0, 1, 2, 3, 4, or 5;

[0663] R 3 R 4 R 5 R 6 Each is independently selected from H and R X2 ;

[0664] R X2 Each time it appears, it is independently selected from halogen, -NO2, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -OR 7 -SR 7 -NR 7 R 8 -C(=O)OR 7 -C(=O)NR 7 R 8 -OC(=O)R 7 -NC(=O)R 7 R 8 -C(=O)R 7 -S(=O)2OR 7 -S(=O)2R 7 -S(=O)2NR 7 R 8 -OS(=O)2R 7 -NS(=O)2R 7 R 8 -S(=O)R 7 The alkyl, alkenyl, or alkynyl group is optionally selected from one or more halogens, -NO2, -CN, -OH, -O(C 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4alkylene groups (-(tri- to seven-membered heterocyclic groups), -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 alkylene (tri- to seven-membered heterocyclic groups) 2, =O, -COOH and C 1-6 Alkyl substituents;

[0665] R 7 R 8 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl or heterocyclic group is optionally selected from one or more halogens, -NO2, -CN, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)O(C 1-6 Alkyl), -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-OC(=O)(C 1-6 Alkyl), -NHC(=O)(C 1-6 Alkyl), -C(=O)(C 1-6 Substitution of alkyl groups;

[0666] R a1 R b1 R c1 R a2 R b2 R c2 Each time it appears, it is independently selected from H and C. 1-6 Alkyl, C 2-6 alkenyl, C2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, C 6-10 Aryl, C 6-10 Aryl-C 1-4 Alkyl, five- to ten-membered heteroaryl, five- to ten-membered heteroaryl-C 1-4 Alkyl, -OR Y1 -SR Y1 -NR Y1 R Y2 -C(=O)OR Y1 -C(=O)NR Y1 R Y2 -C(=O)R Y1 -S(=O)2OR Y1 -S(=O)2R Y1 -S(=O)2NR Y1 R Y2 -S(=O)R Y1 The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are optionally selected from one or more halogens, =O, =S, -OR. Y3 -SR Y3 -NR Y3 R Y4 -C(=O)R Y3 -C(=O)OR Y3 and -C(=O)NR Y3 R Y4 Substituents of the substituents;

[0667] R Y1 R Y2 R Y3 R Y4 As mentioned above <1> or <2> Defined in the document;

[0668] Specifically, the structure of equation (9) is as follows:

[0669]

[0670] <7> The above <1> or <2> The compound or its pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite or prodrug, wherein the structure of the LCM moiety is as shown in formula (10), or is a pharmaceutically acceptable salt thereof.

[0671]

[0672] Among them, R20 The atom is selected from bicyclic heteroaryl groups, having 9-10 ring atoms, including 1-3 heteroatoms each independently selected from oxygen, sulfur, and nitrogen, with the remaining atoms being carbon atoms; the heteroaryl group is unsubstituted or has at least one atom selected from R. X3 Substitution of groups;

[0673] R 21 Selected from C 1-8 alkyl;

[0674] R 22 Selected from R X3 ;

[0675] R 23 It is a phenyl group, which is unsubstituted or contains at least one component selected from R. X3 Substitution of groups;

[0676] R X3 Each time it appears, it is independently selected from C. 1-8 Alkyl, C 1-8 Alkenyl, halogen, -CN, -CF3, -CHF2, -CH2F, -NO2, -OH, -O(C 1-8 Alkyl), -SH, -S(C 1-8 Alkyl groups, -NH2, -NH(C) 1-8 alkyl), -N(C) 1-8 Alkyl group 2, -COOH, -C(=O)O(C 1-8 Alkyl), -C(=O)NH(C 1-8 Alkyl), -C(=O)N(C 1-8 Alkyl)2, -S(=O)2OH, -S(=O)2(OC 1-8 Alkyl groups), -S(=O)2NH2, -S(=O)2NH(C 1-8 Alkyl), -S(=O)2N(C 1-8 Alkyl group 2; wherein the alkyl group is optionally composed of one or more elements selected from halogen, -NO2, -CN, C 1-8 Alkyl, -OH, -O(C) 1-8 Alkyl), -SH, -S(C 1-8 Alkyl groups, -NH2, -NH(C) 1-8 alkyl), -N(C) 1-8 Substitution with alkyl groups (2), =O, and -COOH;

[0677] p is 0, 1, or 2;

[0678] Specifically, the structure of equation (10) is as follows:

[0679]

[0680] <8> The above <1> or <2> The compound or its pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite or prodrug, wherein the structure of the LCM moiety is as shown in formula (11), or is a pharmaceutically acceptable salt thereof:

[0681]

[0682] Among them, R 24 Selected from ternary to 7-membered heterocyclic groups; said heterocyclic group is unsubstituted or substituted with at least one group selected from R X3 Substitution of groups;

[0683] L 3 Choose any C 1-8 alkylene and a C 3-6 Combinations of cycloalkyl groups;

[0684] R 25 Selected from H, C 1-8 alkyl;

[0685] R 26 Selected from halogens, -NO2, -CN, C 1-8 Alkyl, -OH, -O(C) 1-8 Alkyl), -SH, -S(C 1-8 Alkyl groups, -NH2, -NH(C) 1-8 alkyl), -N(C) 1-8 Alkyl)2;

[0686] L 4 Selected from C 1-8 Alkylene and C 1-8 alkoxy subunit;

[0687] R 27 It is a phenyl group, which is unsubstituted or contains at least one component selected from R. X3 Substitution of groups;

[0688] q is 0, 1, or 2;

[0689] R X3 As mentioned above <7> Defined in the document;

[0690] Specifically, the structure of equation (11) is as follows:

[0691]

[0692] <9> The above <1> or <2> The compound or its pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite or prodrug, wherein the LCM moiety has the structure of the following formula (12), or is a pharmaceutically acceptable salt thereof:

[0693]

[0694] Among them, R 28 C 1-8 alkenyl; the alkenyl group is formed by at least one C 1-8 Alkyl substitution, wherein the alkyl group is optionally replaced by one or more selected from R X4 Substitution of groups;

[0695] R 29 Selected from H, C 1-8 alkyl;

[0696] R 30 Selected from halogens, -NO2, -CN, C 1-8 Alkyl, -OH, -O(C) 1-8 Alkyl), -SH, -S(C 1-8 Alkyl groups, -NH2, -NH(C) 1-8 alkyl), -N(C) 1-8 Alkyl)2;

[0697] L 5 Selected from -O-, C 1-8 Alkylene and C 1-8 alkoxy subunit;

[0698] R 31 Selected from six-membered heteroaryl groups, having six ring atoms, including one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen, with the remaining atoms being carbon atoms, wherein the heteroaryl group is unsubstituted or has at least one heteroatom selected from R. X3 Substitution of groups;

[0699] r can be 0, 1, 2, 3, or 4;

[0700] s can be 0, 1, 2, 3, or 4;

[0701] R X4 Each time it appears, it is independently selected from C. 1-8 Alkyl, C 1-8 Alkenyl, halogen, -CN, -CF3, -CHF2, -CH2F, -NO2, -O(C 1-8 alkyl), -S(C 1-8 alkyl), -NH(C) 1-8 alkyl), -N(C) 1-8 Alkyl)2、-OC(=O)(C1-8 Alkyl), -NHC(=O)(C 1-8 Alkyl), -NC (=O) (C 1-8 Alkyl)2, -OS(=O)2(C 1-6 Alkyl), -NHS(=O)2(C 1-8 alkyl), -N(C) 1-8 Alkyl)S(=O)2(C 1-8 Alkyl group; wherein the alkyl group is optionally composed of one or more elements selected from halogens, -NO2, -CN, C 1-8 Alkyl, -OH, -O(C) 1-8 Alkyl), -SH, -S(C 1-8 Alkyl groups, -NH2, -NH(C) 1-8 alkyl), -N(C) 1-8 Substitution with alkyl groups (2), =O, and -COOH;

[0702] R X3 As mentioned above <7> Defined in the document;

[0703] Specifically, the structure of equation (12) is as follows:

[0704]

[0705] <10> The above <1> or <2> The compound or its pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite or prodrug, wherein the structure of the LCM moiety is as shown in formula (13), or is a pharmaceutically acceptable salt thereof:

[0706]

[0707] Among them, R 32 Selected from ternary to 7-membered heterocyclic groups; said heterocyclic group is unsubstituted or substituted with at least one group selected from R X3 Substitution of groups;

[0708] L 6 Selected from -O-, C 1-8 Alkylene and C 1-8 alkoxy subunit;

[0709] R 33 R 34 Selected from halogens, C 1-8 alkyl;

[0710] R 35 Selected from halogens, -NO2, -CN, C 1-8 Alkyl, -OH, -O(C) 1-8 Alkyl), -SH, -S(C 1-8Alkyl groups, -NH2, -NH(C) 1-8 alkyl), -N(C) 1-8 Alkyl)2;

[0711] R 36 The compound is selected from five-membered heteroaryl groups, which have five ring atoms, including one to three heteroatoms each independently selected from oxygen, sulfur, and nitrogen, and the remaining atoms are carbon atoms. The heteroaryl group is unsubstituted or has at least one heteroatom selected from R. X3 Substitution of groups;

[0712] t can be 0, 1, 2, or 3;

[0713] u can be 0, 1, 2, 3 or 4;

[0714] R X3 As mentioned above <7> Defined in the document;

[0715] Specifically, the structure of equation (13) is as follows:

[0716]

[0717] <11> The above <1> or <2> The compound or its pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite or prodrug, wherein the structure of the LCM moiety is as shown in formula (14), or is a pharmaceutically acceptable salt thereof:

[0718]

[0719] Among them, R 37 Selected from six-membered heteroaryl groups, having six ring atoms, including one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen, with the remaining atoms being carbon atoms. The heteroaryl group is unsubstituted or substituted with at least one atom selected from halogen, -NO2, -CN, or C. 1-8 Alkyl, -OH, -O(C) 1-8 Alkyl), -SH, -S(C 1-8 Alkyl groups, -NH2, -NH(C) 1-8 alkyl), -N(C) 1-8 Substitution of alkyl groups;

[0720] R 38 R 39 R 40 Each independently selected from R X3 ;

[0721] R 41The compound is selected from five-membered heteroaryl groups, which have five ring atoms, including one to three heteroatoms each independently selected from oxygen, sulfur, and nitrogen, and the remaining atoms are carbon atoms. The heteroaryl group is unsubstituted or has at least one heteroatom selected from R. X3 Substitution of groups;

[0722] v can be 0, 1, 2, or 3;

[0723] w can be 0, 1, 2, 3, or 4;

[0724] x is 0, 1, 2, 3 or 4;

[0725] R X3 As mentioned above <7> Defined in the document;

[0726] Specifically, the structure of equation (14) is as follows:

[0727]

[0728] <12> The above <1> - <11> The compound of any one of the following, or its pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite, or prodrug, wherein in formula (I)

[0729] L is a chemical bond, or a straight-chain or branched hydrocarbon group containing 1-60, preferably 1-30, more preferably 2-16 carbon atoms, wherein each carbon atom is optionally replaced by one or more, for example 1-3, preferably 1-2, particularly 1 heteroatom; wherein the heteroatom is selected from oxygen, sulfur, nitrogen, phosphorus, preferably oxygen, sulfur, or nitrogen, more preferably oxygen or nitrogen, particularly oxygen; wherein the carbon atom or heteroatom is optionally replaced by one or more selected from R L1 R L2 R L3 R L4 and R L5 The group is substituted; wherein

[0730] R L1 R L2 R L3 R L4 and R L5 Each is independently selected from: H, halogen, C 1-6 Alkyl, -O(C) 1-6 Alkyl), -S(C) 1-6 alkyl), -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, C 3-6 cycloalkyl, C 6-10 Aryl, five- to seven-membered heteroaryl, three- to seven-membered heterocyclic, -O(C 3-6 cycloalkyl), -S(C 3-6cycloalkyl), -NH(C 3-6 cycloalkyl), -N(C) 3-6 cycloalkyl)2, -N(C 3-6 cycloalkyl)(C 1-6 Alkyl groups, -OH, -NH2, -SH, -S(=O)2(C 1-6 Alkyl), -P(=O)(OC 1-6 Alkyl)(C 1-6 Alkyl), -P(=O)(OC 1-6 Alkyl)2、-C≡CC 1-6 Alkyl group, -C≡CH, -CH=CH(C) 1-6 alkyl), -C(C 1-6 Alkyl)=CH(C 1-6 alkyl), -C(C 1-6 Alkyl) = C(C 1-6 Alkyl group 2, -Si(OH)3, -Si(C) 1-6 Alkyl)3、-Si(OH)(C 1-6 Alkyl)2、-C(=O)(C 1-6 Alkyl groups, -COOH, halogens, -CN, -CF3, -CHF2, -CH2F, -NO2, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl), -S(=O)N(C 1-6 Alkyl)2、-C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(=O)NH(C 1-6 alkyl), -N(C) 1-6 Alkyl)C(=O)N(C 1-6 Alkyl)2、-NHC(=O)NH(C 1-6 Alkyl), -NHC(=O)N(C 1-6 Alkyl)2, -NHC(=O)NH2, -N(C 1-6 alkyl)S(=O)2NH(C 1-6 alkyl), -N(C) 1-6 Alkyl)S(=O)2N(C 1-6 alkyl)2、-NHS(=O)2NH(C 1-6 Alkyl), -NHS(=O)2N(C 1-6 Alkyl)2 and NHS(=O)2NH2;

[0731] Preferably, L is a straight-chain group.

[0732] <13> The above <1> - <12> The compound of any one of the following, or its pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite or prodrug, wherein the TM part is selected from lipid droplet probes, compounds that can bind lipid droplet labeled proteins, and compounds that can bind neutral fatty acids in lipid droplets.

[0733] Preferably, the lipid droplet probe is selected from Sudan I, Sudan II, Sudan III, Oil Red BB, Oil Red O, Sudan Red G, Sudan Black B, Nile Red, 493 / 503, Monodanthyl pentane, PyrPy 10d, PyrPy 11c, PITE, TPE-AmAl, TPA-BI, LipidGreen, LipidGreen2, LD540, AF8, AF10, AFN, NAP AIEgen dye, LD-BTD1, LipiDye, Phos 2a, Phos 2b, Phos 3a, Phos 3b, SF44, SF58, FAS, DPAS, BTD-coumarin hybrid, IND-TPA, photoactivated AIE probe, LD-TPZn, LQD, photoactivated AIEgen probe, TPE-AC, TPMN, TTMN, MeTTMN, MeOTTMN, DCMa, DCI, DCFu, NLV-1, StatoMerocynaine dye (SMCy dye);

[0734] The NAP AIEgen dye is preferably selected from NAP-Ph, NAP-Br, NAP-CF3, and NAP-Py;

[0735] The BTD-coumarin hybrid is preferably BTD-Lip;

[0736] The photoactivated AIE probe is preferably BZT 3a;

[0737] The photoactivatable AIEgen probe is preferably PhotoAFN 2a-c;

[0738] The SMCy dye is preferably selected from SMCy 3 and SMCy 5.5;

[0739] Specifically, the TM portion is selected from Sudan I, Sudan II, Sudan III, Oil Red BB, Oil Red O, Sudan Red G, and Sudan Black B; preferably selected from Oil Red O and Oil Red BB, especially Oil Red BB.

[0740] <14> The above <1> - <13> The TM moiety is a compound or a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite, or prodrug thereof, wherein the TM moiety is a structure of formula (II) or a conjugate or hybrid formed by the interconnection of two or more structures of formula (II).

[0741]

[0742] in:

[0743] The E ring and F ring are each independently selected from the benzene ring and the naphthalene ring; wherein the E ring is optionally composed of one or more rings selected from the R ring. E The F ring is optionally replaced by one or more groups selected from R. F The G ring is optionally replaced by one or more groups selected from R. G Substitution of groups;

[0744] The G ring is absent, or is selected from the benzene ring and the naphthalene ring;

[0745] Z 1 It is an azo group;

[0746] Z 2 It does not exist, or it may be an azo group;

[0747] R E R F and R G Each occurrence is independently selected from H, halogen, -NO2, -CN, =O, =S, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 Cyclic hydrocarbon group), -O (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6 -Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 alkyl), -N(C) 1-6 alkyl)-(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cyclic hydrocarbon group), -N(C) 1-6 alkyl)-(C=O)(C 3-6 cyclic hydrocarbon group), -NH (C=O)(C 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-6 alkyl)-(C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -NH (C=O) (three- to seven-membered heterocyclic groups), -N (C 1-6 Alkyl)-(C=O) (three to seven-membered heterocyclic groups), -COOH, -C(=O) (C 1-6 Alkyl), -C(=O)O(C 1-6 Alkyl), -C(=O)O(C 3-6 cyclic hydrocarbon group), -C(=O)O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -C(=O)O (three- to seven-membered heterocyclic groups), -C(=O)O (C 1-4 Alkylene group (ternary to seven-membered heterocyclic group), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-C(=O)NH(C 1-4Alkylene-C 3-6 cyclic hydrocarbon group), -C(=O)N(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -C(=O)NH (three- to seven-membered heterocyclic group), -C(=O)N (three- to seven-membered heterocyclic group)2, -C(=O)NH (C 1-4 alkylene-tertiary to seven-membered heterocyclic groups), -C(=O)N(C 1-4 alkylene-tertiary to heptaneous groups) 2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl), -S(=O)N(C 1-6 Alkyl)2, wherein the alkyl, alkylene, alkenyl, alkynyl, cycloalkyl or heterocyclic group is optionally selected from one or more halogens, nitro, cyano, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Substitution of alkyl group 2; or

[0748] Two Rs E Two Rs F Or two Rs G They are interconnected, forming carbon together with the atoms they are connected to. 3-10 Hydrocarbon ring or three- to seven-membered heterocycle, wherein the hydrocarbon ring or heterocycle is optionally surrounded by one or more elements selected from halogen, nitro, cyano, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6Alkyl), -S(=O)2N(C 1-6 Alkyl)2 substituents.

[0749] <15> The above <14> The compound (II) is a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite, or prodrug thereof, wherein formula (II) has the structure of formula (III) as follows.

[0750]

[0751] Where R 42 R 43 R 44 R 45 R 46 R 47 R 48 R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 Each is independently selected from H, halogens, -NO2, -CN, =O, =S, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 Cyclic hydrocarbon group), -O (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6-Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (-(tri- to seven-membered heterocyclic groups), -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 alkyl), -N(C) 1-6 alkyl)-(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cyclic hydrocarbon group), -N(C) 1-6 alkyl)-(C=O)(C 3-6 cyclic hydrocarbon group), -NH (C=O)(C 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-6 alkyl)-(C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -NH (C=O) (three- to seven-membered heterocyclic groups), -N (C 1-6 Alkyl)-(C=O) (three to seven-membered heterocyclic groups), -COOH, -C(=O) (C 1-6 Alkyl), -C(=O)O(C 1-6 Alkyl), -C(=O)O(C 3-6 cyclic hydrocarbon group), -C(=O)O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -C(=O)O (three- to seven-membered heterocyclic groups), -C(=O)O (C 1-4 Alkylene group (ternary to seven-membered heterocyclic group), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-C(=O)NH(C 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -C(=O)N(C 1-4 Alkylene-C 3-6Cyclic hydrocarbon group)2, -C(=O)NH (three- to seven-membered heterocyclic group), -C(=O)N (three- to seven-membered heterocyclic group)2, -C(=O)NH (C 1-4 alkylene-tertiary to seven-membered heterocyclic groups), -C(=O)N(C 1-4 alkylene-tertiary to heptaneous groups) 2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl), -S(=O)N(C 1-6 Alkyl)2, wherein the alkyl, alkylene, alkenyl, alkynyl, cycloalkyl or heterocyclic group is optionally selected from one or more halogens, nitro, cyano, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups, -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Substitution of alkyl group 2; or

[0752] Selected from R 42 R 43 R 44 R 45 R 46 R 47 R 48 R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 Two adjacent groups are linked together, forming a carbon atom along with the atoms they are attached to. 3-10 Hydrocarbon ring or three- to seven-membered heterocycle, wherein the hydrocarbon ring or heterocycle is optionally surrounded by one or more elements selected from halogen, nitro, cyano, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6Alkyl group 2, -COOH, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Substitution of alkyl group 2;

[0753] Preferably, R 42 R 43 R 44 R 45 R 46 R 47 and R 48 At least one of them is -Cl, -Br, -I, -NO2, -CN, =O, =S, -OH, -O(C 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-NH(C=O)(C 1-6 alkyl), -N(C) 1-6 alkyl)-(C=O)(C 1-6 Alkyl group, -COOH group, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2, -S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl) or -S(=O)N(C 1-6 Alkyl group 2, the remaining groups are each independently selected from H, halogen, -NO2, -CN, =O, =S, C 1-6 Alkyl, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-NH(C=O)(C 1-6 alkyl), -N(C) 1-6 alkyl)-(C=O)(C 1-6 Alkyl group, -COOH group, -C(=O)(C 1-6 Alkyl groups), -C(=O)NH2, -C(=O)NH(C1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2-S(=O)2OH, -S(=O)2NH(C 1-6 Alkyl), -S(=O)2N(C 1-6 Alkyl)2、-S(=O)NH(C 1-6 Alkyl), -S(=O)N(C 1-6 Alkyl group 2, wherein the alkyl group is optionally composed of one or more elements selected from halogen, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution with alkyl groups (-2), -COOH, or -S(=O)2OH; or, selected from R 42 R 43 R 44 R 45 R 46 R 47 and R 48 Preferably selected from R 44 and R 45 Two adjacent groups are linked together, forming a carbon atom along with the atoms they are attached to. 3-10 Hydrocarbon ring or three- to seven-membered heterocycle, wherein the hydrocarbon ring or heterocycle is optionally surrounded by one or more elements selected from halogens, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution with alkyl groups ()2, -COOH, -S(=O)2OH; and R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 For H, or R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 At least one of them, preferably 1-6, more preferably 1-4, and particularly preferably 1, 2, or 4 are C. 1-6 Alkyl or -O(C) 1-6 Alkyl group, preferably C1-3 Alkyl or -O(C) 1-3 Alkyl), wherein C 1-3 Alkyl groups are particularly preferred to be methyl groups, -O(C 1-3 Alkyl groups are particularly preferred, with methoxy groups being selected independently from H, halogens, C, and so on. 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl groups, preferably selected from H and halogens, particularly preferably H; wherein the alkyl group is optionally surrounded by one or more elements selected from halogens, -OH, -O(C) 1-6 Alkyl), -SH, -S(C 1-6 Alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Substitution of alkyl group 2;

[0754] Specifically, formula (III) is selected from:

[0755]

[0756]

[0757] Preferably selected from in particular

[0758] <16> The above <14> The compound (II) is a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite, or prodrug thereof, wherein formula (II) has the structure of formula (IV).

[0759]

[0760] Where R 42 R 43 R 44 R 45 R 46 R 47 R 48 R 53 R 54 R 55 R 56 and R 57 As mentioned above <11> Defined in [the document / reference].

[0761] Specifically, formula (IV) is selected from:

[0762]

[0763] <17> The above <14> The compound (II) is a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, tautomer, isotopic compound, metabolite, or prodrug thereof, wherein formula (II) has the structure of formula (V).

[0764]

[0765] Where R 42 R 43 R 44 R 45 R 46 R 47 R 48 R 53 R 54 R 55 R 56 and R 57 As mentioned above <11> Defined in the document;

[0766] Where R 58 R 59 R 60 R 61 R 62 and R 63 Each is independently selected from H, halogens, -NO2, -CN, =O, =S, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cyclic hydrocarbon group, C 3-6 Cyclic hydrocarbon group -C 1-4 Alkyl, three- to seven-membered heterocyclic groups, three- to seven-membered heterocyclic groups -C 1-4 Alkyl, -OH, -O(C) 1-6 alkyl), -O(C) 3-6 cyclic hydrocarbon group), -O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (three- to seven-membered heterocyclic groups), -O (C 1-4 alkylene)-(tertiary to seven-membered heterocyclic groups), -O(C=O)(C 1-6 Alkyl), -O (C=O) (C 3-6 Cyclic hydrocarbon group), -O (C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -O (C=O) (three- to seven-membered heterocyclic groups), -O (C=O) (C 1-4 alkylene groups (-(ternary to seven-membered heterocyclic groups), -SH, -S(C) 1-6 alkyl), -S(C 3-6 cyclic hydrocarbon group), -S(C 1-4 Alkylene-C 3-6-Cyclohydryl groups), -S (tri- to seven-membered heterocyclic groups), -S (C 1-4 alkylene groups (ternary to seven-membered heterocyclic groups), -NH2, -NH(C 1-6 alkyl), -N(C) 1-6 alkyl)2、-NH(C 3-6 cyclic hydrocarbon group), -N(C) 3-6 2, -NH(C) 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-4 Alkylene-C 3-6 Cyclic hydrocarbon group)2, -NH (three- to seven-membered heterocyclic group), -N (three- to seven-membered heterocyclic group)2, -NH (C 1-4 alkylene-tertiary to heptaneous groups), -N(C 1-4 2, -NH(C=O)(C 1-6 alkyl), -N(C) 1-6 alkyl)-(C=O)(C 1-6 Alkyl), -NH(C=O)(C 3-6 cyclic hydrocarbon group), -N(C) 1-6 alkyl)-(C=O)(C 3-6 cyclic hydrocarbon group), -NH (C=O)(C 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -N(C) 1-6 alkyl)-(C=O)(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -NH (C=O) (three- to seven-membered heterocyclic groups), -N (C 1-6 Alkyl)-(C=O) (three to seven-membered heterocyclic groups), -COOH, -C(=O) (C 1-6 Alkyl), -C(=O)O(C 1-6 Alkyl), -C(=O)O(C 3-6 cyclic hydrocarbon group), -C(=O)O(C 1-4 Alkylene-C 3-6 Cyclic hydrocarbon groups), -C(=O)O (three- to seven-membered heterocyclic groups), -C(=O)O (C 1-4 Alkylene group (ternary to seven-membered heterocyclic group), -C(=O)NH2, -C(=O)NH(C 1-6 Alkyl), -C(=O)N(C 1-6 Alkyl)2、-C(=O)NH(C 1-4 Alkylene-C 3-6 cyclic hydrocarbon group), -C(=O)N(C 1-4 Alkylene-C 3-6Cyclic hydrocarbon group)2, -C(=O)NH (three- to seven-membered heterocyclic group), -C(=O)N (three- to seven-membered heterocyclic group)2, -C(=O)NH (C 1-4 alkylene-tertiary to sev...

Claims

1. A compound or a pharmaceutically acceptable salt thereof, said compound having a structure comprising formula (I). LCM―L―TM(I) in: LCM is the LC3 binding site, which is the part that has an affinity for the LC3 protein; L represents the connector section; TM represents the lipid droplet binding region, which is the part that can non-covalently interact with the lipid droplets; Wherein, the formula (I) has the structure of the following formula (xv): in: L is a structure of formula (a) or a pharmaceutically acceptable salt thereof: -Dy-(a) Where y is an integer greater than 1; and y is an integer less than or equal to 12; Each D is independently selected from the following groups: -CR L1 R L2 -, -O-, -S-, -S(=O)-, -NR L3 -、-C(=O-、Optional location with 0-6 R L1 and / or R L2 Group-substituted four- to six-membered heterocyclic groups, optionally via 0-6 R groups L1 and / or R L2 Group-substituted heteroaryl groups; wherein, R L1 R L2 R L3 Each is independently selected from: H, C 1-6 Alkyl, -OH, -NH2, -SH, halogen, -CN; The LCM portion is selected from the following structure: The E ring and F ring are each independently selected from the benzene ring and the naphthalene ring; wherein the E ring is optionally composed of one or more rings selected from the R ring. E The F ring is optionally replaced by one or more groups selected from R. F The G ring is optionally replaced by one or more groups selected from R. G Substitution of groups; The G ring is absent, or is selected from the benzene ring and the naphthalene ring; Z 1 It is an azo group; Z 2 It does not exist, or it may be an azo group; R E R F and R G Each time it appears, it is independently selected from H and C. 1-6 Alkyl groups and -OH.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein: D is selected independently from -CR L1 R L2 - and -O-.

3. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein, The R L1 and R L2 For H.

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein, The structure of L is selected from 5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein, The R L1 R L2 and R L3 For H.

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein, The structure of L is as follows:

7. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein, The TM portion is selected from Sudan III and Sudan IV.

8. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein, The TM part is Sudan III.

9. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein formula (I) has the structure of formula (xvi): Where R 42 R 43 R 44 R 45 R 46 R 47 R 48 R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 Each is independently selected from H and C. 1-6 Alkyl groups and -OH.

10. The compound of claim 9 or a pharmaceutically acceptable salt thereof, wherein, The R 42 R 43 R 44 R 45 R 46 R 47 and R 48 At least one of them is -OH; and R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 For H.

11. The compound of claim 9 or a pharmaceutically acceptable salt thereof, wherein, The R 42 R 43 R 44 R 45 R 46 R 47 and R 48 At least one of them is -OH; and, the R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 At least one of them is C 1-6 Alkyl groups, and the remaining groups are each independently selected from H.

12. The compound of claim 11 or a pharmaceutically acceptable salt thereof, wherein, The R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 At least one of them is C 1-3 Alkyl groups, and the remaining groups are each independently selected from H.

13. The compound of claim 11 or a pharmaceutically acceptable salt thereof, wherein, The R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 At least one of them is a methyl group, and the remaining groups are each independently selected from H.

14. The compound of claim 11 or a pharmaceutically acceptable salt thereof, wherein, The R 49 R 50 R 51 R 52 R 53 R 54 R 55 R 56 and R 57 Two of them are C 1-6 Alkyl groups, and the remaining groups are each independently selected from H.

15. The compound of claim 9 or a pharmaceutically acceptable salt thereof, wherein, The formula (xvi) is selected from:

16. The compound of claim 15 or a pharmaceutically acceptable salt thereof, wherein, The equation (xvi) is 17. The compound of any one of claims 1-16 or a pharmaceutically acceptable salt thereof, wherein said compound is selected from...

18. A pharmaceutical composition comprising a preventive or therapeutically effective amount of the compound of any one of claims 1-17 or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

19. The use of any compound of claims 1-17 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 18, in the preparation of a medicament for treating lipid metabolism-related diseases.

20. The application according to claim 19, wherein, The lipid metabolism-related diseases mentioned are selected from MADD, obesity, NAFLD, type II diabetes, hepatocellular carcinoma, Alzheimer's disease, and atherosclerosis.

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