Imidazolidinedione HDAC inhibitor, and preparation method therefor and use thereof

Abstract

The present invention belongs to the technical field of medicines. The present invention relates to an imidazolidinedione HDAC inhibitor, and a preparation method therefor and the use thereof. Provided in the present invention is an imidazolidinedione HDAC inhibitor, which inhibitor is a substituted imidazolidinedione compound as represented by general formula V, or a stereoisomer, a hydrate or a pharmaceutically acceptable salt thereof. The inhibitor has efficient and good HDAC enzyme inhibitory activity, and also has good in-vitro anti-tumor activity. The inhibitor provides a new way for the application of an HDAC inhibitor in tumors / or the treatment of diseases related to uncontrolled histone deacetylase activity.

Description

Imidazolidinedione HDAC inhibitor, preparation method and application Technical Field

[0001] The present invention relates to an imidazolidinedione HDAC inhibitor, a preparation method and an application thereof, and belongs to the technical field of medicine. Background Art

[0002] Traditional treatments for malignant tumors primarily include surgery, chemotherapy, and radiotherapy. While surgery is a promising approach, it is not ideal for prolonging life without other adjuvant therapies. Chemotherapy can lead to drug resistance and side effects, including bone marrow suppression and intestinal dysfunction. Radiotherapy is a localized treatment that can inhibit tumor growth but can also affect and damage surrounding tissues. Molecularly targeted therapies, with their high specificity and low toxicity, have become a new approach for cancer treatment. In chemotherapy, inhibition of histone deacetylase has been extensively studied and demonstrated promising therapeutic effects in a wide range of cancers. Despite over three decades of research, existing clinical candidate HDAC inhibitors still suffer from poor pharmacokinetic properties, limited efficacy, and limited indications. The potential for combination therapy with HDAC targets has not been fully realized, and there are relatively few marketed HDAC inhibitors. Therefore, this target remains of great research value and potential for further investigation. Histone deacetylase (HDAC), discovered in the 1990s, plays a crucial role in post-translational modification of amino acid side chains in a wide range of proteins, enabling them to exist in multiple states and significantly altering their biological properties. Because histone deacetylases are highly expressed in a wide range of tumor cells, HDAC inhibitors can effectively target tumor cells without causing significant toxicity. Furthermore, HDACs can slow and minimize the process by which cancer stem cells acquire drug resistance. Prostate cancer is the second most common male cancer worldwide (after lung cancer), most commonly occurring in men over 50 years of age. While prostate cancer is often curable when it hasn't metastasized, approximately 25% of cases do. These patients often remain asymptomatic for months or even years in the early stages, making treatment and diagnosis more difficult. Initial treatment can be achieved through androgen deprivation, but this can easily lead to drug resistance, making the disease incurable. Research is currently exploring the potential benefits of HDAC inhibitors for prostate cancer patients. First, overexpression of HDAC6 is associated with the invasion and metastasis of tumor cells, and HDAC overexpression is often observed in prostate cancer patients. Second, HDAC exhibits high levels of inhibition in multiple tumor systems. A considerable number of academic studies have provided experimental evidence for the use of HDAC inhibitors in the treatment of prostate cancer. At the same time, HDAC inhibitors can solve the drug resistance problem of many inhibitors, but there are no HDAC inhibitors specifically for prostate cancer. Summary of the Invention

[0003] The purpose of the present invention is to address the defects of the prior art and to provide an imidazolidinedione HDAC inhibitor, a preparation method and an application thereof.

[0004] The present invention solves the technical problem through the following technical solution: The imidazolidinedione HDAC inhibitor of the present invention is a substituted imidazolidinedione compound represented by general formula V, or a stereoisomer, hydrate or pharmaceutically acceptable salt thereof: wherein W is selected from an oxygen atom or a sulfur atom; X, Y, Z, M1, and M2 each independently represent a carbon or nitrogen atom, and when X, Y, Z, M1, and M2 are carbon atoms, each independently is optionally substituted by R3, and R3 can be hydrogen, alkyl, cyano, halogen, haloalkyl, hydroxyl, sulfhydryl, alkoxy, alkylthio, alkoxyalkyl, aralkyl, aryl, or Het; Q is selected from a saturated or unsaturated straight or branched hydrocarbon group having a length of 1 to 9 carbon atoms, an aryl, or Het; R1 is hydrogen, deuterium, alkyl, haloalkyl, hydroxyl, sulfhydryl, alkoxy, alkylamino, alkylthio, alkoxyalkyl, methylene, aralkyl, diarylalkyl, aryl, or Het; R2 is selected from a hydroxyl group, a 2-aminophenyl group optionally substituted by one or more R4; R4 is hydrogen, alkyl, cyano, halogen, haloalkyl, hydroxyl, sulfhydryl, alkoxy, alkylthio, alkoxyalkyl, aralkyl, aryl, or Het; Alkyl is a straight or branched saturated hydrocarbon group having 1 to 9 carbon atoms; or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms; or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms attached to a straight or branched saturated hydrocarbon group having 1 to 6 carbon atoms; Alkoxy is a straight or branched saturated hydrocarbon group having 1 to 9 carbon atoms or a cyclic saturated hydrocarbon group having 3 to 9 carbon atoms; or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms attached to a straight or branched saturated hydrocarbon group having 1 to 9 carbon atoms; wherein each carbon atom is optionally substituted with oxygen; Alkylamino is a straight or branched saturated hydrocarbon group having 1 to 9 carbon atoms or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms; or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms attached to a straight or branched saturated hydrocarbon group having 1 to 9 carbon atoms; wherein each carbon atom is optionally substituted with an NH group; Alkoxyalkyl is an alkoxy group as defined above attached to an alkyl group; Alkenyl and alkynyl are straight or branched unsaturated hydrocarbon groups having 1 to 9 carbon atoms and containing double or triple bonds; aryl is a carbocyclic ring selected from phenyl, naphthyl, acenaphthyl or tetrahydronaphthyl, each of which is optionally substituted with 1, 2 or 3 substituents, each of which is independently selected from hydrogen, alkyl, cyano, halogen, haloalkyl, hydroxy, mercapto, alkoxy, alkylthio, alkoxyalkyl, aralkyl, diarylalkyl, aryl or Het; aralkyl and diarylalkyl are aryl groups as defined above linked to an alkyl group; Het is a monocyclic heterocycle selected from pyrrolyl, pyrazolyl, imidazolyl, furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl; or a bicyclic heterocycle selected from quinolyl, quinoxalinyl, indolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzofuranyl, benzothienyl, 2,3-dihydrobenzo[1,4]dioxinyl or benzo[1,3]dioxolyl;or a monocyclic saturated hydrocarbon group of 3-6 carbon atoms or a bicyclic saturated hydrocarbon group of 6-12 carbon atoms, wherein the carbon atoms in the ring are independently optionally substituted with 1-4 O, S, N or NH; each monocyclic or bicyclic ring is optionally substituted with 1, 2 or 3 substituents, each substituent being independently selected from halogen, haloalkyl, hydroxy, alkyl or alkoxy.;

[0005] Halogen is a substituent selected from fluorine, chlorine, bromine or iodine; haloalkyl is a straight-chain or branched saturated hydrocarbon group having 1 to 9 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms, or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms connected to a straight-chain or branched saturated hydrocarbon group having 1 to 6 carbon atoms; wherein one or more carbon atoms are substituted by one or more halogen atoms.

[0006] Preferably, the present invention further selects the following compounds as imidazolidinedione HDAC inhibitors: wherein W is selected from an oxygen atom or a sulfur atom; X, Y, Z, M1, and M2 each independently represent a carbon or nitrogen atom; when X, Y, Z, M1, and M2 are carbon atoms, each independently is optionally substituted by R3, and R3 is hydrogen, alkyl, cyano, halogen, haloalkyl, alkoxy, alkylthio, or alkoxyalkyl; Q is selected from a saturated or unsaturated straight-chain or branched hydrocarbon group with a length of 1 to 9 carbon atoms, or an aryl group; R2 is selected from a hydroxyl group, or a 2-aminophenyl group optionally substituted with one or more R4; and R4 is hydrogen, alkyl, cyano, halogen, haloalkyl, aryl, or Het.

[0007] Preferably, the present invention further selects the following compounds as imidazolidinedione HDAC inhibitors: wherein W is selected from an oxygen atom or a sulfur atom; X, Y, Z, M1, and M2 each independently represent a carbon or nitrogen atom; when X, Y, Z, M1, and M2 are carbon atoms, each independently is optionally substituted by R3, and R3 is hydrogen, alkyl, halogen, or alkoxy; Q is selected from a saturated or unsaturated straight-chain or branched hydrocarbon group or an aryl group having a length of 3 to 9 carbon atoms; R2 is selected from a hydroxyl group or a 2-aminophenyl group optionally substituted with one or more R4; and R4 is hydrogen, alkyl, cyano, halogen, haloalkyl, aryl, or Het.

[0008] Preferably, in the inhibitor of formula V, the hydrogen attached to carbon is replaced by deuterium, an isotope of hydrogen.

[0009] More preferably, the alkyl group is replaced by a deuterated alkyl group, the alkoxy group is replaced by a deuterated epoxy group, the benzene ring is replaced by a deuterated benzene ring, and the aromatic ring is replaced by a deuterated aromatic ring.

[0010] Preferably, a pharmaceutically acceptable salt refers to a salt form in which a basic group in the parent compound is converted; wherein the pharmaceutically acceptable salt is an inorganic or organic acid salt of a basic group, more preferably an amine or amino group; the basic group in the parent compound reacts with 1-4 equivalents of an acid in a solvent system.

[0011] Preferably, the basic group of the compound of the present invention can form a salt with an acid, and the acid salt is specifically a salt formed with an inorganic acid, especially a hydrohalic acid (such as hydrochloric acid, hydrobromic acid, hydroiodic acid), nitric acid, sulfuric acid, phosphoric acid, carbonic acid, etc.; a salt formed with a lower alkyl sulfonic acid, such as methanesulfonic acid, trifluoromethanesulfonic acid; a salt formed with an aryl sulfonic acid, such as benzenesulfonic acid or p-toluenesulfonic acid; a salt formed with an organic acid, such as acetic acid, fumaric acid, tartaric acid, oxalic acid, citric acid, maleic acid, malic acid or succinic acid; a salt formed with an amino acid, such as aspartic acid or glutamic acid.

[0012] Preferably, the compounds and pharmaceutically acceptable salts of the present invention also include solvate or hydrate forms.

[0013] Preferably, the structural formula of the compound in the imidazolidinedione HDAC inhibitor of the present invention includes isomeric forms, such as enantiomers, diastereomers, geometric isomers or conformational isomers, specifically R and S configurations containing asymmetric centers, (Z) and (E) isomers of double bonds, and (Z) and (E) conformational isomers.

[0014] Preferably, the inhibitor is one of the following: (1) (Z)-N-hydroxy-7-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)heptylamide; (2) (Z)-N-hydroxy-8-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)octanamide; (3) (Z)-N-hydroxy-6-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (4) (Z)-N-hydroxy-5-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)pentanamide; (5) (Z)-N-hydroxy-7-(4-(4-bromo-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)heptylamide; (6) (Z)-N-hydroxy-8-(4-(4-bromo-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)octanamide; (7) (Z)-N-hydroxy-9-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)nonanamide; (8) (Z)-N-hydroxy-10-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)decanamide; (9) (Z)-N-hydroxy-7-(4-(2-methoxybenzylidene)-3-methyl-2,5-dioxoimidazolidin-1-yl)heptanamide; (10) (Z)-N-hydroxy-7-(4-(4-bromo-2-methoxybenzylidene)-3-methyl-2,5-dioxoimidazolidin-1-yl)heptanamide; (11) (Z)-N-hydroxy-6-(4-(4-bromo-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (12) (Z)-N-hydroxy-6-(4-(3-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (13) (Z)-N-hydroxy-6-(4-(4-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (14) (Z)-N-hydroxy-6-(4-(2,4-dimethoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (15) (Z)-N-hydroxy-6-(4-(4-fluoro-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (16) (Z)-N-Hydroxy-6-(4-(4-chloro-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (17) (Z)-N-Hydroxy-6-(4-(2-methoxy-4-methylbenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (18) (Z)-N-Hydroxy-6-(4-(2-methoxy-4-(trifluoromethyl)benzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (19) (Z)-N-Hydroxy-6-(2,5-dioxo-4-(3,4,5-trimethoxybenzylidene)imidazolidin-1-yl)hexanamide;(20) (Z)-N-Hydroxy-6-(4-(naphthalen-1-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (21) (Z)-N-Hydroxy-6-(4-(naphthalen-2-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (22) (Z)-N-Hydroxy-6-(2,5-dioxo-4-(quinolin-2-ylmethylene)imidazolidin-1-yl)hexanamide; (23) (Z)-N-Hydroxy-6-(2,5-dioxo-4-(quinolin-3-ylmethylene)imidazolidin-1-yl)hexanamide; (24) (Z)-N-Hydroxy-6-(2,5-dioxo-4-(quinolin-4-ylmethylene)imidazolidin-1-yl)hexanamide; (25) (Z)-N-Hydroxy-6-(2,5-dioxo-4-(quinolin-6-ylmethylene)imidazolidin-1-yl)hexanamide; (26) (Z)-N-Hydroxy-6-(2,5-dioxo-4-(quinolin-5-ylmethylene)imidazolidin-1-yl)hexanamide; (27) (Z)-N-Hydroxy-6-(4-(furan-2-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (28) (Z)-N-Hydroxy-6-(2,5-dioxo-4-(thiophen-2-ylmethylene)imidazolidin-1-yl)hexanamide; (29) (Z)-N-Hydroxy-6-(4-((2,3-dihydrobenzofuran-5-yl)methylene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (30) (Z)-N-hydroxy-6-(4-(benzofuran-5-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (31) (Z)-N-hydroxy-6-(4-(benzo[d][1,3]dioxol-5-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (32) (Z)-N-hydroxy-6-(4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methylene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (33) (Z)-N-(2-amino-4-fluorophenyl)-4-((2,5-dioxo-4-(pyridin-3-ylmethylene)imidazolidin-1-yl)methyl)benzamide; (34) (Z)-N-(2-amino-4-fluorophenyl)-4-((2,5-dioxo-4-(pyridin-3-ylmethylene)imidazolidin-1-yl)methyl)benzamide; (35) (Z)-N-hydroxy-6-(2,5-dioxo-4-((4-(pyridin-4-yl)quinolin-6-yl)methylene)imidazolidin-1-yl)hexanamide.

[0015] The preparation method of the above-mentioned inhibitor is as follows: using substituted formaldehyde (A) and hydroxylamine or substituted hydroxylamine (B) as raw materials, a Knoevenagel condensation reaction occurs in the presence of alanine to obtain an intermediate (C); the intermediate (C) undergoes a nucleophilic substitution reaction with a bromocarboxylate to obtain a key intermediate (D); the intermediate (D) undergoes a hydrolysis reaction under acidic conditions to obtain an intermediate (E); and the intermediate (E) undergoes a condensation reaction with hydroxylamine hydrochloride to obtain the target compound (1-32). The synthetic route is as follows:

[0016] The above-mentioned inhibitor is prepared by two methods. Using substituted formaldehyde (A) and hydantoin or substituted hydantoin (B) as raw materials, a Knoevenagel condensation reaction occurs under the action of alanine to obtain an intermediate (C); the intermediate (C) undergoes a nucleophilic substitution reaction with a bromocarboxylate to obtain a key intermediate (D); the intermediate (D) undergoes a hydrolysis reaction under acidic conditions to obtain an intermediate (E); the intermediate (E) undergoes a condensation reaction with 4-fluoro-1,2-phenylenediamine to obtain the target compound (1-32). The synthetic route is as follows:

[0017] The preparation method of the above-mentioned inhibitor also includes the following steps: using compound (F) as a raw material, reacting it with cycloisopropyl malonate to undergo a Combes quinoline synthesis reaction to obtain intermediate (G); brominating intermediate (G) with phosphorus tribromide in DMF to obtain intermediate (H); Suzuki coupling reaction of intermediate (H) with 4-pyridineboronic acid to obtain intermediate (I); reducing intermediate (I) with lithium aluminum hydride to obtain intermediate (J); and selectively oxidizing intermediate (J) to obtain key intermediate (K). Intermediate (K) undergoes four steps to obtain target compound (35), and the synthesis route is as follows:

[0018] Use of the above-mentioned imidazolidinedione HDAC inhibitor in the preparation of a drug for inhibiting the growth of cancer cells.

[0019] Based on the weak inhibitory activity and insufficient anti-tumor effect of HDAC, the present invention selected vorinostat as a lead compound for further structural modification. The basic skeleton structure was determined to be imidazolidinedione, and by screening substituent groups, a highly effective inhibitory effect was achieved.

[0020] Compared with the prior art, the present invention has the following significant advantages: (1) it has highly efficient and excellent HDAC enzyme inhibitory activity; (2) it has low cost, good efficacy, low toxicity, and a high yield of intermediate products during the synthesis process, which reduces resource waste and is conducive to reducing costs; (3) it has significant anti-tumor activity and a small dosage. DETAILED DESCRIPTION

[0021] The technical solution of the present invention will be further described below in conjunction with embodiments.

[0022] Reagents were purchased from commercial suppliers such as Anhui Zesheng Technology Co., Ltd., Bailingwei Technology Co., Ltd., Aladdin Reagent Co., Ltd., and Beijing Coupling Technology Co., Ltd., and were used without further purification unless otherwise indicated. General reagents were purchased from Xilong Chemical Co., Ltd., Nanjing Chemical Reagent Co., Ltd., Sinopharm Chemical Reagent Co., Ltd., and Qingdao Ocean Chemical Co., Ltd. In the examples, all temperatures are in degrees Celsius unless otherwise indicated. In the examples described below, silica gel columns were used as chromatographic columns. Silica gel (200-300 mesh) was purchased from Qingdao Ocean Chemical Co., Ltd. Nuclear magnetic resonance spectra were performed using CDCl3 or DMSO-d6 as solvents (in ppm) and TMS (0 ppm) as the reference standard. When multiple peaks are present, the following abbreviations are used: s (singlet), d (doublet), t (triplet), m (multiplet), br (broadened), dd (doublet of doublets), and dt (doublet of triplets). The coupling constant is expressed in Hertz (Hz).

[0023] The low-resolution mass spectrometry (MS) data in the examples described below were analyzed using an Agilent 6120 series LC-MS equipped with a G1329B autosampler and a G4212B detector using a G1311B quaternary pump and a G1316A column oven. An ESI source was used for the LC-MS spectrometer.

[0024] For ease of description, some of the raw materials in the examples described below will be described by their abbreviations, which are compared with their full names as follows: DCM is CH2Cl2, i.e., dichloromethane; CDCl3 is deuterated chloroform; PE is petroleum ether; EtOAc and EA are both ethyl acetate; MeOH and CH3OH are both methanol; ClSO3H is chlorosulfonic acid; TEA and Et3N are triethylamine; DMSO-d6 is hexadeuterated dimethyl sulfoxide; THF is tetrahydrofuran; NaCl is sodium chloride; Na2SO4 is sodium sulfate; DIPEA is N,N-diisopropylethylamine, PyBOP is 1H-benzotriazol-1-yloxytripyrrolidino hexafluorophosphate, and Pd(dppf)Cl2 is 1,1′-bis(diphenylphosphino)ferrocenepalladium chloride, dichloromethane complex. Example 1

[0025] The synthesis steps for (Z)-N-hydroxy-7-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)heptamide are as follows: Step 1: Synthesis of (Z)-5-(2-methoxybenzylidene)imidazolidine-2,4-dione, with the following structural formula: 1.11 g of 2-methoxybenzaldehyde (10 mmol), 1.36 g (11.0 mmol, 1.1 eq.) of hydantoin, and 1.07 g (12.0 mmol, 1.2 eq.) of β-alanine were dissolved in 25 mL of acetic acid in a 100 mL eggplant-shaped reaction flask. The mixture was refluxed at 120°C overnight and the reaction was continued by TLC until the starting material was completely consumed. The reaction solution was slowly added to ice water and stirred at room temperature. A large amount of solid precipitated, which was filtered to obtain the crude product. The crude product was purified by silica gel column chromatography (PE:EA = 1:1). The product was a pale yellow solid with a yield of 76%. 1H NMR (300 MHz, Chloroform-d) δ 9.62 (s, 1H), 9.05 (s, 1H), 7.67 (dd, J = 7.8, 1.6 Hz, 1H), 7.37 (td, J = 7.8, 1.5 Hz, 1H), 7.07 (td, J = 7.6, 1.2 Hz, 1H), 7.00 (dd, J = 8.1, 1.3 Hz, 1H), 6.88 (s, 1H), 3.87 (s, 2H). Step 2: Synthesis of ethyl (Z)-7-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)heptanoate, the structural formula is as follows: Weigh 5 mmol of (Z)-5-(2-methoxybenzylidene)imidazolidine-2,4-dione and 10 mmol of potassium carbonate (2.0 eq.) in 20 mL of DMF. The mixture was cooled to 0°C and stirred for 30 minutes. Then, 6 mmol of ethyl 7-bromoheptanoate (1.2 eq.) was slowly added dropwise. The temperature was raised to room temperature and the reaction was continued for 6-8 hours. After the reaction, the product was purified by column chromatography (PE:EA = 5:1-2:1). The product was obtained as a white solid in a 52% yield. 1 H NMR (400MHz, Chloroform-d) δ8.00 (s, 1H), 7.41-7.33 (m, 2H), 7.08-6.95 (m, 2H), 6.76 (s, 1H), 4.13 (q, J=7.1Hz, 2H), 3.96 (s, 3H), 3.61 (dd, J=8.0, 6.6Hz, 2H), 2.30 (t, J=7.5Hz, 2H), 1.76 (s, 1H), 1.75-1.58 (m, 4H), 1.43-1.33 (m, J=4.0, 3.5Hz, 4H), 1.26 (t, J=7.1Hz, 4H). Step 3: Synthesis of (Z)-N-hydroxy-7-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)heptylamide, the structural formula of which is as follows: First, (Z)-7-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)heptanoic acid was prepared. 5 mmol of ethyl (Z)-7-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)heptanoate was dissolved in 10 mL of acetic acid solution and placed in a 50 mL eggplant-shaped flask. 1 mL of concentrated hydrochloric acid was slowly added dropwise to the reaction flask. The reaction temperature was raised to 90°C and the reaction was carried out for 6 hours. After the reaction was completed, the reaction solution was added to ice brine while hot to precipitate a large amount of white solid, which was then dried to obtain a crude product of (Z)-7-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)heptanoic acid. Weigh 1 mmol of crude (Z)-7-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)heptanoic acid and 1.5 mmol of PyBOP condensing agent (1.5 eq.) into a 25 mL reaction vial. Add 6 mL of DMF solution and 590 μL of DIPEA (3.5 eq.). Stir at room temperature for several minutes, then add 0.14 g of hydroxylamine hydrochloride (2.0 eq.). React at room temperature for 6 h, monitor by TLC until the intermediate is completely consumed (DCM:MeOH = 25:1). Concentrate in vacuo and purify by column chromatography. The resulting product is a white solid in a 53% yield. 1 H NMR (400MHz, DMSO-d6) δ10.60 (d, J = 3.5Hz, 1H), 10.32 (d, J = 3.5Hz, 1H), 8.52 (s, 1H), 7. 66 (dd, J=7.7, 1.6Hz, 1H), 7.37 (td, J=7.8, 1.6Hz, 1H), 7.07 (td, J=7.6, 1.2Hz, 1H), 7.0 0 (dd, J=8.0, 1.3Hz, 1H), 6.86 (s, 1H), 3.87 (s, 2H), 3.72 (t, J=6.6Hz, 2H), 1.99 (t, J=8. 6Hz, 2H), 1.62 (p, J=6.7Hz, 2H), 1.55 (ddd, J=16.3, 8.5, 7.4Hz, 2H), 1.41-1.28 (m, 4H); 13 C NMR (101 MHz, DMSO-d6) δ 174.79, 163.98, 158.56, 154.37, 132.25, 129.69, 127.13, 124.90, 123.38, 112.63, 110.42, 55.63, 37.80, 32.04, 28.24, 27.26, 26.86, 25.05. Example 2

[0026] (Z)-N-Hydroxy-8-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)octanamide, the structural formula is as follows: The fragment 7-bromoheptanoic acid ethyl ester in step 2 of Example 1 was replaced with 8-bromooctanoic acid ethyl ester, and the other steps and operations were the same as those in Example 1; a white solid was obtained, with a yield of 43%. 1 H NMR (400MHz, DMSCO-d6) δ10.45 (d, J=3.5Hz, 1H), 9.08 (d, J=3.5Hz, 1H), 8.52 (s, 1H), 7.62 (dd, J=7.7, 1.6Hz, 1H), 7.34 (td, J=7.9, 7.3, 1.6Hz, 1H ), 7.09-6.95 (m, 2H), 6.74 (s, 1H), 3.85 (s, 3H), 3.46 (t, J=7.1Hz, 2H), 1. 93 (t, J=7.4Hz, 2H), 1.51 (dp, J=29.4, 7.2Hz, 4H), 1.25 (h, J=6.0Hz, 6H); 13 C NMR (101 MHz, DMSO-d6) δ 174.80, 163.98, 158.56, 154.37, 132.25, 129.69, 127.13, 124.90, 123.38, 112.63, 110.42, 55.63, 37.80, 32.04, 28.81, 27.94, 27.26, 27.07, 25.05. Example 3

[0027] (Z)-N-Hydroxy-6-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidinazole-1-yl)hexanamide, the structural formula is as follows: The fragment 7-bromoheptanoic acid ethyl ester in step 2 of Example 1 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1. The product was a white solid with a yield of 47%. 1 H NMR (400MHz, DMSO-d6) δ10.45 (d, J=3.5Hz, 1H), 8.69 (d, J=3.7Hz, 1H), 7.61 ( dd, J=7.7, 1.6Hz, 1H), 7.34 (ddd, J=8.7, 7.4, 1.6Hz, 1H), 7.05 (dd, J=8.4, 1.1 Hz, 1H), 6.98 (td, J=7.4, 1.0Hz, 1H), 6.73 (s, 1H), 3.84 (s, 3H), 3.44 (t, J=7. 1Hz, 3H), 2.01-1.89 (m, 2H), 1.51 (dq, J=15.1, 7.5Hz, 4H), 1.30-1.13 (m, 2H); 13C NMR (101 MHz, DMSO-d6) δ 169.72, 164.59, 157.59, 155.51, 130.87, 129.71, 126.96, 121.62, 121.08, 111.59, 104.57, 56.07, 38.28, 32.50, 27.81, 26.15, 24.61. Example 4

[0028] (Z)-N-Hydroxy-5-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)pentanamide, the structural formula is as follows: The fragment 7-bromoheptanoic acid ethyl ester in step 2 of Example 1 was replaced with 5-bromopentanoic acid ethyl ester, and the other steps and operations were the same as those in Example 1; a white solid was obtained, with a yield of 48%. 1 H NMR (40MHz, DMSO-d6) δ10.36 (d, J=3.5Hz, 1H), 9.08 (d, J=3.5Hz, 1H), 8.52 (s, 1H), 7.61 (dd, J=7.7, 1.6Hz, 1H), 7.35 (ddd, J=8.7, 7.4, 1.6Hz, 1H), 7.06 (dd, J=8.4, 1.0Hz, 1H), 6.99 (td, J=7.5, 1.0Hz, 1H), 6.74 (s, 1H), 3.85 (s, 3H), 3.4 6(t, J=6.5Hz, 2H), 1.98 (t, J=6.2Hz, 2H), 1.50 (ddt, J=15.7, 12.1, 8.2Hz, 4H); 13 C NMR (101 MHz, DMSO-d6) δ 170.22, 164.78, 157.53, 155.60, 131.19, 129.64, 126.68, 121.34, 121.20, 111.63, 105.46, 56.02, 38.13, 32.13, 27.54, 22.82. Example 5

[0029] (Z)-N-Hydroxy-7-(4-(4-bromo-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)heptylamide, the structural formula is as follows: Replace the raw material in step 1 in Example 1 with 2-methoxybenzaldehyde and 4-bromo-2-methoxybenzaldehyde, and the other steps and operations are the same as in Example 1; white solid, yield: 38%. 1H NMR (400MHz, DMSO-d6) δ10.60 (d, J=3.5Hz, 1H), 10.32 (d, J=3.5Hz, 1H), 8.51 (s, 1H), 7.52 (d, J=9.0Hz, 1H), 7.40 (dd, J=8.8, 2.2Hz, 1H), 7.23 (d, J=2.2Hz, 1H), 6.85 (s, 1H), 3.88 (s, 2H), 3.72 (t, J=6.6Hz, 2H), 1.99 (t, J=8.6Hz, 2H), 1.62 (p, J=6.7Hz, 2H), 1.55 (ddd, J=16.3, 8.5, 7.4Hz, 2H), 1.41-1.28 (m, 4H); 13 CNMR (101 MHz, DMSO-d6) δ 178.26, 162.10, 156.21, 152.45, 135.20, 124.25, 123.56, 123.21, 120.64, 112.11, 111.87, 56.07, 36.50, 32.64, 27.97, 27.02, 26.66, 25.14. Example 6

[0030] (Z)-N-Hydroxy-8-(4-(4-bromo-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)octanamide, the structural formula is as follows: The raw material in step 1 of Example 1 was replaced with 2-methoxybenzaldehyde or 4-bromo-2-methoxybenzaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 8-bromooctanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; a white solid was obtained with a yield of 35%. 1 H NMR (400MHz, DMSO-d6) δ10.58 (d, J=3.5Hz, 1H), 10.30 (d, J=3.5Hz, 1H), 8.53 (s, 1H), 7.50 (d, J=9.0Hz, 1H), 7.42 (dd, J=8.8, 2.2Hz, 1H ), 7.21 (d, J = 2.2Hz, 1H), 6.83 (s, 1H), 3.76 (s, 2H), 3.70 (t, J = 6.6Hz, 2H), 2.01 (t, J = 8.6Hz, 2H), 1.66-1.49 (m, 4H), 1.43-1.23 (m, 7H); 13C NMR (101 MHz, DMSO-d6) δ 169.66, 164.44, 158.25, 155.49, 131.06, 127.61, 123.88, 123.25, 121.16, 114.92, 103.14, 56.67, 38.40, 32.68, 28.91, 28.69, 28.01, 26.52, 25.51. Example 7

[0031] (Z)-N-Hydroxy-9-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)nonanamide, the structural formula is as follows: The fragment 7-bromoheptanoic acid ethyl ester in step 2 of Example 1 was replaced with 9-bromononanoic acid ethyl ester. Other steps and operations were the same as those in Example 1. The product was a white solid with a yield of 39%. 1 H NMR (400MHz, DMSO-d6) δ10.62 (d, J=3.5Hz, 1H), 10.32 (d, J=3.5Hz, 1H), 8.66 (s , 1H), 7.60 (dd, J=7.6, 1.6Hz, 1H), 7.39-7.29 (m, 1H), 7.05 (d, J=8.3Hz, 1H), 6.9 8 (t, J=7.5Hz, 1H), 6.73 (s, 1H), 3.84 (s, 3H), 3.45 (t, J=7.1Hz, 2H), 1.92 (t, J=7 .3Hz, 2H), 1.55 (q, J=7.0Hz, 2H), 1.46 (p, J=7.5, 7.0Hz, 2H), 1.28-1.20 (m, 8H); 13 C NMR (101 MHz, DMSO-d6) δ 169.71, 164.55, 157.61, 155.50, 130.79, 129.74, 126.98, 121.68, 121.05, 111.59, 104.42, 56.08, 38.35, 32.68, 29.05, 28.96, 28.89, 28.01, 27.91, 26.58, 25.55. Example 8

[0032] (Z)-N-Hydroxy-10-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)decylamide, the structural formula is as follows: The fragment 7-bromoheptanoic acid ethyl ester in step 2 of Example 1 was replaced with 10-bromodecanoic acid ethyl ester, and the other steps and operations were the same as those in Example 1; a white solid was obtained, with a yield of 32%. 1H NMR (400MHz, DMSO-d6) δ10.63 (d, J=3.5Hz, 1H), 10.32 (d, J=3.5Hz, 1H), 8.6 6 (s, 1H), 7.60 (dd, J=7.7, 1.6Hz, 1H), 7.39-7.29 (m, 1H), 7.05 (d, J=8.3Hz, 1 H), 6.98 (t, J=7.5Hz, 1H), 6.73 (s, 1H), 3.84 (s, 3H), 3.45 (t, J=7.1Hz, 2H), 1.92 (t, J=7.4Hz, 2H), 1.50 (dp, J=33.1, 7.0Hz, 4H), 1.24 (d, J=8.0Hz, 10H); 13 C NMR (101 MHz, DMSO-d6) δ 169.64, 164.54, 157.62, 155.49, 130.76, 129.75, 127.00, 121.71, 121.04, 111.58, 104.35, 56.08, 38.35, 32.71, 29.27, 29.14, 29.01, 28.96, 28.01, 26.71, 25.57. Example 9

[0033] (Z)-N-Hydroxy-7-(4-(2-methoxybenzylidene)-3-methyl-2,5-dioxoimidazolidin-1-yl)heptylamide, the structural formula is as follows: The raw material hydantoin in step 1 of Example 1 was replaced with 1-methylhydantoin, and the other steps and operations were the same as those in Example 1; a white solid was obtained, with a yield of 34%. 1 H NMR (400MHz, DMSO-d6) δ10.62 (d, J=3.5Hz, 1H), 10.32 (d, J=3.5Hz, 1H), .52s, 1H ), 7.71 (dd, J=7.7, 1.6Hz, 1H), 7.37 (td, J=7.8, 1.6Hz, 1H), 7.36 (s, 1H), 7.07 (t d, J=7.6, 1.2Hz, 1H), 7.00 (dd, J=8.1, 1.3Hz, 1H), 3.87 (s, 2H), 3.72 (t, J=6.7Hz , 2H), 3.300 (s, 2H), 1.99 (t, J=8.6Hz, 2H), 1.66-1.50 (m, 4H), 1.41-1.28 (m, 4H); 13C NMR (101 MHz, DMSO-d6) δ 169.54, 163.56, 161.67, 157.47, 131.35, 131.26, 130.75, 129.45, 121.50, 120.34, 111.34, 56.02, 38.90, 32.63, 30.09, 28.57, 27.96, 26.65, 25.43. Example 10

[0034] (Z)-N-Hydroxy-7-(4-(4-bromo-2-methoxybenzylidene)-3-methyl-2,5-dioxoimidazolidin-1-yl)heptylamide, the structural formula is as follows: The raw material hydantoin in step 1 of Example 1 was changed to 1-methylhydantoin, and 2-methoxybenzaldehyde was changed to 4-bromo-2-methoxybenzaldehyde. The other steps and operations were the same as in Example 1; white solid, yield: 35%. 1 H NMR (400MHz, DMSO-d6) δ10.34 (d, J=3.3Hz, 1H), 8.67 (d, J=3.5Hz, 1H), 7.88 (d, J=9.0Hz, 1H), 7.24 (s, 1H), 7.13 (dd, J=9.0, 2.2Hz, 1H) ; 13 C NMR (101 MHz, DMSO-d6) δ 169.57, 163.47, 158.56, 153.56, 132.71, 130.04, 123.28, 123.05, 120.99, 114.72, 114.43, 56.60, 38.93, 32.63, 30.14, 28.56, 27.93, 26.67, 25.41. Example 11

[0035] (Z)-N-Hydroxy-6-(4-(4-bromo-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw material in step 1 of Example 1 was replaced with 2-methoxybenzaldehyde or 4-bromo-2-methoxybenzaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; a white solid was obtained with a yield of 40%. 1H NMR (400MHz, DMSO-d6) δ10.60 (d, J=3.5Hz, 1H), 8.76 (d, J=3.5Hz, 1H), 8.43 (s, 1H), 7.51 (d, J=9.0Hz, 1H), 7.30 (dd, J=9.0, 2.0Hz, 1H) ; 13 C NMR (101 MHz, DMSO-d6) δ 169.80, 165.71, 158.87, 155.31, 134.44, 127.54, 124.90, 124.46, 122.70, 118.04, 112.23, 57.17, 36.98, 33.77, 27.55, 26.54, 24.60. Example 12

[0036] (Z)-N-Hydroxy-6-(4-(3-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw material in step 1 of Example 1 was replaced with 2-methoxybenzaldehyde or 3-methoxybenzaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; a white solid was obtained with a yield of 39%. 1 H NMR (400MHz, DMSO-d6) δ10.62 (d, J=3.3Hz, 1H), 8.92 (d, J=3.5Hz, 1H), 8.79 (s, 1H), 7.26 (ddd, J=8.0, 7.0, 1.0Hz, 1H), 7.15 (dt, J=8.1, 2. 5Hz, 1H), 7.02-6.96 (m, 2H), 6.65 (s, 1H), 3.82 (s, 2H), 3.72 (t, J=6.6Hz, 2H), 1.99 (t, J=8.6Hz, 2H), 1.68-1.56 (m, 4H), 1.44-1.29 (m, 2H); 13 C NMR (101 MHz, DMSO-d6) δ 169.20, 160.57, 159.87, 155.68, 134.71, 130.75, 126.30, 124.62, 119.25, 118.51, 116.35, 52.27, 37.70, 36.52, 27.81, 26.68, 25.41. Example 13

[0037] (Z)-N-Hydroxy-6-(4-(4-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw material in step 1 of Example 1 was replaced with 2-methoxybenzaldehyde or 4-methoxybenzaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; a white solid was obtained with a yield of 38%. 1 H NMR (400MHz, DMSO-d6) δ10.56 (d, J=3.3Hz, 1H), 9.20 (d, J=3.5Hz, 1H), 8.82 (s, 1H), 7.56-7.50 (m, 2H), 7.08-7.01 (m , 2H), 6.59 (s, 1H), 3.82 (s, 2H), 3.72 (t, J=6.6Hz, 2H), 1.99 (t, J=8.6Hz, 2H), 1.67-1.52 (m, 4H), 1.42-1.33 (m, 2H); 13 C NMR (101 MHz, DMSO-d6) δ 1700.80, 168.10, 164.70, 150.38, 134.53, 129.69, 125.16, 119.05, 114.85, 56.32, 36.80, 31.22, 27.21, 26.48, 24.81. Example 14

[0038] (Z)-N-Hydroxy-6-(4-(2,4-dimethoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide, the structural formula is as follows. The raw material in step 1 of Example 1 was replaced with 2-methoxybenzaldehyde or 2,4-dimethoxybenzaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; a white solid was obtained with a yield of 42%. 1 H NMR (400MHz, DMSO-d6) δ10.52 (d, J=3.5Hz, 1H), 9.02 (d, J=3.5Hz, 1H), 8.56 (s, 1H), 7.53 (d, J=8.2Hz, 1H), 6.74 (s, 1H), 6.63 -6.56 (m, 2H), 3.88 (s, 2H), 3.82 (s, 2H), 3.72 (t, J=6.6Hz, 2H), 1.99 (t, J=8.6Hz, 2H), 1.64-1.50 (m, 4H), 1.47-1.32 (m, 2H); 13C NMR (101 MHz, DMSO-d6) δ 169.57, 164.50, 160.87, 154.92, 152.61, 135.81, 129.45, 121.12, 115.45, 110.55, 100.21, 58.67, 53.12, 39.71, 33.55, 29.45, 26.53, 25.12. Example 15

[0039] (Z)-N-Hydroxy-6-(4-(4-fluoro-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw material in step 1 of Example 1 was replaced with 2-methoxybenzaldehyde or 4-fluoro-2-methoxybenzaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; the product was a pale yellow solid with a yield of 40%. 1 H NMR (400MHz, DMSO-d6) δ10.54 (d, J=3.5Hz, 1H), 9.08 (d, J=3.5Hz, 1H), 8.51 (s, 1H), 7.52 (dd, J=8.7, 5.0Hz, 1H), 7.00 (ddd, J=8.8, 8 .1, 1.9Hz, 1H), 6.81-6.76 (m, 2H), 3.77 (s, 2H), 3.54 (t, J=6.6Hz, 2H), 2.00 (t, J=8.6Hz, 2H), 1.64-1.50 (m, 4H), 1.39-1.29 (m, 2H); 13 C NMR (101 MHz, DMSO-d6) δ 169.40, 165.87, 164.98, 163.92, 160.22, 157.95, 153.67, 131.80, 131.21, 128.05, 122.61, 120.67, 113.06, 111.05, 109.97, 101.65, 101.42, 52.05, 38.51, 33.34, 28.05, 27.48, 25.21. Example 16

[0040] (Z)-N-Hydroxy-6-(4-(4-chloro-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw material in step 1 of Example 1 was replaced with 2-methoxybenzaldehyde or 4-chloro-2-methoxybenzaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; a white solid was obtained with a yield of 36%. 1H NMR (400MHz, DMSO-d6) δ10.62 (d, J=3.5Hz, 1H), 9.08 (d, J=3.5Hz, 1H), 8.60 (s, 1H), 7.54 (d, J=8.8Hz, 1H), 7.34-7.28 (m, 1H), 7.0 2 (d, J=1.9Hz, 1H), 6.82 (s, 1H), 3.98 (s, 2H), 3.70 (t, J=6.6Hz, 2H), 1.98 (t, J=8.6Hz, 2H), 1.64-1.50 (m, 4H), 1.41-1.30 (m, 2H); 13 C NMR (101 MHz, DMSO-d6) δ 169.50, 166.58, 160.54, 159.70, 136.08, 132.87, 128.71, 124.33, 120.71, 111.45, 110.12, 52.10, 38.70, 35.44, 29.02, 27.52, 25.21. Example 17

[0041] (Z)-N-Hydroxy-6-(4-(2-methoxy-4-methylbenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw material in step 1 of Example 1 was replaced with 2-methoxybenzaldehyde or 2-methoxy-4-methylbenzaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; a white solid was obtained with a yield of 41%. 1 H NMR (400MHz, DMSO-d6) δ10.61 (d, J=3.5Hz, 1H), 8.86 (d, J=3.5Hz, 1H), 8.53 (s, 1H), 7. 66 (dd, J=7.7, 1.6Hz, 1H), 7.31 (td, J=7.8, 1.6Hz, 1H), 7.09 (td, J=7.6, 1.2Hz, 1H), 7.0 0 (dd, J=8.0, 1.3Hz, 1H), 6.84 (s, 1H), 3.89 (s, 2H), 3.70 (t, J=6.6Hz, 2H), 1.97 (t, J=8. 6Hz, 2H), 1.60 (p, J=6.7Hz, 2H), 1.52 (ddd, J=16.3, 8.5, 7.4Hz, 2H), 1.40-1.27 (m, 4H); 13C NMR (101 MHz, DMSO-d6) δ 169.80, 160.98, 156.66, 152.37, 138.67, 124.59, 124.11, 122.41, 121.85, 112.05, 111.02, 54.50, 34.80, 31.22, 26.86, 26.42, 25.11, 22.78. Example 18

[0042] (Z)-N-Hydroxy-6-(4-(2-methoxy-4-(trifluoromethyl)benzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw material in step 1 of Example 1 was replaced with 2-methoxybenzaldehyde or 2-methoxy-4-trifluoromethylbenzaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; the product was a pale yellow solid with a yield of 43%. 1 H NMR (400MHz, DMSO-d6) δ10.54 (d, J=3.5Hz, 1H), 9.00 (d, J=3.5Hz, 1H), 8.52 (s, 1H), 7.60 (d, J=1.5Hz, 2H), 7.31-7.27 (m, 1H), 6.82 (s, 1H), 3.98 (s, 2H), 3.75 (t, J=6.6Hz, 2H), 2.02 (t, J=8.6Hz, 2H), 1.69-1.54 (m, 4H), 1.44-1.35 (m, 2H); 13 C NMR (101MHz, DMSO-d6) δ169.40, 163.98, 158.10, 158.08, 158.06, 158.05, 154. 37, 132.84, 132.59, 132.33, 132.07, 129.17, 129.15, 129.14, 129.12, 127.11, 1 Example 19

[0043] (Z)-N-Hydroxy-6-(2,5-dioxo-4-(3,4,5-trimethoxybenzylidene)imidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw materials in step 1 of Example 1 were replaced with 2-methoxybenzaldehyde and 3,4,5-trimethoxybenzaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; a white solid was obtained with a yield of 34%. 1 H NMR (400MHz, DMSO-d6) δ10.57 (d, J=3.3Hz, 1H), 9.02 (d, J=3.5Hz, 1H), 8.72 (s, 1H), 7.23 (s, 1H), 6.84 (s, 2H), 3.86 (s, 5H), 3.90 (s, 2H), 3.72 (t, J=6.6Hz, 2H), 1.97 (t, J=8.6Hz, 2H), 1.75-1.64 (m, 4H), 1.48-1.37 (m, 2H); 13 C NMR (101 MHz, DMSO-d6) δ 169.10, 162.70, 155.28, 154.84, 142.12, 131.78, 126.24, 114.45, 109.54, 62.74, 57.42, 36.90, 33.81, 27.87, 27.22, 25.04. Example 20

[0044] (Z)-N-Hydroxy-6-(4-(naphthalen-1-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw materials in step 1 of Example 1 were replaced with 2-methoxybenzaldehyde and 1-naphthaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; the product was a pale yellow solid with a yield of 37%. 1 H NMR (400MHz, DMSO-d6) δ10.85 (d, J=3.3Hz, 1H), 9.10 (d, J=3.5Hz, 1H), 8.87 (s, 1H), 8.10-8.02 (m, 1H), 7.94-7.87 (m, 2H), 7.61 (t, J=7.7Hz, 1H ), 7.60-7.52 (m, 2H), 7.48 (d, J=7.8Hz, 1H), 6.92 (s, 1H), 3.72 (t, J=6.6Hz, 2H), 2.00 (t, J=8.6Hz, 2H), 1.70-1.55 (m, 4H), 1.45-1.36 (m, 2H).; 13C NMR (101 MHz, DMSO-d6) δ 169.87, 161.15, 154.38, 133.08, 132.74, 132.36, 129.24, 128.34, 128.30, 128.25, 126.96, 126.74, 125.72, 124.74, 110.87, 37.80, 32.22, 28.01, 27.29, 25.31. Example 21

[0045] (Z)-N-Hydroxy-6-(4-(naphthalen-2-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw material in step 1 of Example 1 was replaced with 2-methoxybenzaldehyde or 2-naphthaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; the product was a pale yellow solid with a yield of 35%. 1 H NMR (400MHz, DMSO-d6) δ10.58 (d, J=3.3Hz, 1H), 9.02 (d, J=3.5Hz, 1H), 8.89 (s, 1H), 7.98 (dt, J=6.8, 2.0Hz, 1H), 7.87 (ddd, J=5.7, 2.9, 1.2Hz, 2 H), 7.72 (d, J=8.2Hz, 1H), 7.58-7.49 (m, 3H), 6.52 (s, 1H), 3.78 (t, J=6. 6Hz, 2H), 1.97 (t, J=8.6Hz, 2H), 1.69-1.53 ​​(m, 4H), 1.41-1.30 (m, 2H).; 13 C NMR (101 MHz, DMSO-d6) δ 170.80, 166.09, 152.38, 135.52, 135.00, 132.05, 130.06, 129.11, 128.84, 128.28, 127.86, 127.74, 127.64, 118.25, 36.90, 34.35, 26.81, 26.08, 24.81. Example 22

[0046] (Z)-N-hydroxy-6-(2,5-dioxo-4-(quinolin-2-ylmethylene)imidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw material in step 1 of Example 1 was replaced with 2-methoxybenzaldehyde or 2-quinolinecarboxaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; the product was a pale yellow solid with a yield of 31%. 1H NMR (400MHz, DMSO-d6) δ10.76 (d, J=3.3Hz.1H), 9.15 (d, J=3.5Hz, 1H), 8.74 (s, 1H), 8.27 (d, J=8.1Hz, 1H), 8.09-7.99 (m, 1H), 7.95-7.88 (m, 1H), 7.75-7.69(m, 2H), 7.58(s, 1H), 7.51(td, J=7.9, 1.3Hz, 1H), 3.78(t, J= 6.6Hz, 2H), 1.98 (t, J=8.6Hz, 2H), 1.70-1.54 (m, 4H), 1.46-1.32 (m, 2H); 13 C NMR (101 MHz, DMSO-d6) δ 169.89, 164.14, 154.31, 149.81, 147.93, 136.17, 129.80, 128.76, 128.56, 128.53, 126.98, 126.85, 122.01, 108.77, 37.80, 32.22, 28.01, 27.26, 26.86, 25.01. Example 23

[0047] (Z)-N-hydroxy-6-(2,5-dioxo-4-(quinolin-3-ylmethylene)imidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw materials in step 1 of Example 1 were replaced with 2-methoxybenzaldehyde and 3-quinolinecarboxaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; the product was a pale yellow solid with a yield of 32%. 1 H NMR (400MHz, DMSO-d6) δ10.65 (d, J=3.3Hz, 1H), 9.12 (d, J=3.5Hz, 1H), 8.92 (s, 1H), 8 .80 (d, J=2.0Hz, 1H), 8.38 (t, J=1.9Hz, 1H), 8.10 (dt, J=8.2, 1.8Hz, 1H), 8.02 (dd, J= 7.2, 1.3Hz, 1H), 7.68 (td, J=7.5, 1.3Hz, 1H), 7.62 (td, J=8.2, 1.4Hz, 1H), 6.87 (s, 1H ), 3.84 (t, J=6.6Hz, 2H), 2.00 (t, J=8.6Hz, 2H), 1.65-1.48 (m, 4H), 1.40-1.30 (m, 2H); 13C NMR (101 MHz, DMSO-d6) δ 171.80, 166.12, 151.38, 148.02, 147.33, 132.67, 128.95, 128.65, 128.56, 128.43, 127.44, 126.81, 126.60, 113.70, 38.87, 33.54, 27.87, 27.27.25.31. Example 24

[0048] (Z)-N-hydroxy-6-(2,5-dioxo-4-(quinolin-4-ylmethylene)imidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw materials in step 1 of Example 1 were replaced with 2-methoxybenzaldehyde and 4-quinolinecarboxaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; the product was a pale yellow solid with a yield of 30%. 1 H NMR (400MHz, DMSO-d6) δ10.48 (d, J=3.3Hz, 1H), 8.92 (d, J=3.5Hz, 1H), 8.70 (s, 1H), 8 .71 (d, J=4.9Hz, 1H), 8.27-8.15 (m, 1H), 7.95 (dd, J=8.2, 1.5Hz, 1H), 7.61 (ddd, J=8.0 , 6.9, 1.2Hz, 1H), 7.52 (ddd, J=8.2, 7.0, 1.3Hz, 1H), 7.40 (d, J=4.9Hz, 1H), 689 (s, 1H) , 3.72 (t, J=6.6Hz, 2H), 1.97 (t, J=8.6Hz, 2H), 1.60-1.45 (m, 4H), 1.40-1.29 (m, 2H).; 13 C NMR (101 MHz, DMSO-d6) δ 170.80, 162.16, 154.38, 148.08, 148.03, 136.58, 129.92, 129.80, 129.23, 127.88, 127.80, 124.29, 122.99, 111.37, 38.10, 34.55, 27.08, 26.84, 25.01. Example 25

[0049] (Z)-N-hydroxy-6-(2,5-dioxo-4-(quinolin-6-ylmethylene)imidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw materials in step 1 of Example 1 were replaced with 2-methoxybenzaldehyde and 6-quinolinecarboxaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; the product was a pale yellow solid with a yield of 32%. 1H NMR (400MHz, DMSO-d6) δ10.54 (d, J=3.3Hz, 1H), 9.02 (d, J=3.5Hz, 1H), 8.95 (s, 1H), 8.89 (dd, J=4.1, 1.7Hz, 1H), 8.26 (dt, J=8.4, 1.8Hz, 1H), 8.15-8.09 (m, 1H), 8.01 (d, J=8.2Hz, 1H), 7.68 (dd, J=8.2, 2.2Hz, 1H), 7.55 (dd, J=8.2, 4.1Hz, 1H), 6.65 (s, 1H) , 3.70 (t, J=6.6Hz, 2H), 1.98 (t, J=8.6Hz, 2H), 1.69-1.52 (m, 4H), 1.41-1.30 (m, 2H); 13 C NMR (101 MHz, DMSO-d6) δ 169.24, 162.09, 155.38, 148.65, 145.76, 131.38, 130.17, 129.05, 128.37, 127.83, 127.28, 127.27, 122.01, 116.60, 39.40, 34.51, 26.98, 26.64, 25.54. Example 26

[0050] (Z)-N-hydroxy-6-(2,5-dioxo-4-(quinolin-5-ylmethylene)imidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw materials in step 1 of Example 1 were replaced with 2-methoxybenzaldehyde and 8-quinolinecarboxaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; the product was a pale yellow solid with a yield of 30%. 1 H NMR (400MHz, DMSO-d6) δ10.56 (d, J=3.3Hz, 1H), 9.13 (d, J=3.5Hz, 1H), 8.95 (dd, J=4. 2, 1.8Hz, 1H), 8.72 (s, 1H), 8.39 (dd, J=7.6, 1.8Hz, 1H), 8.01 (dd, J=7.2, 1.3Hz, 1H), 7 .65 (dd, J=8.3, 7.2Hz, 1H), 7.57-7.45 (m, 1H), 7.43 (dd, J=7.8, 4.1Hz, 1H), 7.02 (s, 1H ), 3.72 (t, J=6.6Hz, 2H), 1.97 (t, J=8.6Hz, 2H), 1.66-1.50 (m, 4H), 1.45-1.31 (m, 2H); 13C NMR (101 MHz, DMSO-d6) δ 171.01, 163.11, 152.12, 145.24, 144.53, 131.05, 130.12, 129.26, 129.03, 128.51, 128.44, 127.89, 123.40, 111.55, 37.80, 32.22, 27.01, 26.28.24.41. Example 27

[0051] (Z)-N-Hydroxy-6-(4-(furan-2-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw material in step 1 of Example 1 was replaced with 2-methoxybenzaldehyde or 2-furanaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; a dark solid was obtained with a yield of 31%. 1 H NMR (400MHz, DMSO-d6) δ10.66 (d, J=3.3Hz, 1H), 9.06 (d, J=3.5Hz, 1H), 8.75 (s, 1H), 7.89 (t, J=1.5Hz, 1H), 6.96 (dd, J=5.0, 1.2Hz, 1H), 6.76 (s, 1H), 6.58 (dd, J=5.0, 1.7Hz, 1H), 3.70 (t, J=6.6Hz, 2H), 1.99 (t, J=8.6Hz, 2H), 1.66-1.55 (m, 4H), 1.45-1.31 (m, 2H); 13 C NMR (101 MHz, DMSO-d6) δ 172.08, 160.34, 153.38, 151.83, 145.11, 127.00, 115.71, 111.59, 99.81, 37.80, 32.22, 27.01, 26.28, 25.14. Example 28

[0052] (Z)-N-Hydroxy-6-(2,5-dioxo-4-(thien-2-ylmethylene)imidazolidin-1-yl)hexanamide: The raw material in step 1 of Example 1 was replaced with 2-methoxybenzaldehyde or 2-thiophenecarboxaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; yellow solid, yield: 35%. 1H NMR (400MHz, DMSO-d6) δ10.60 (d, J=3.5Hz, 1H), 9.02 (d, J=3.5Hz, 1H), 8.55 (s, 1H), 7. 61 (dd, J=7.7, 1.6Hz, 1H), 7.35 (td, J=7.8, 1.6Hz, 1H), 7.02 (td, J=7.6, 1.2Hz, 1H), 6.9 8 (dd, J=8.0, 1.3Hz, 1H), 6.84 (s, 1H), 3.85 (s, 2H), 3.70 (t, J=6.6Hz, 2H), 1.92 (t, J=8. 6Hz, 2H), 1.61 (p, J=6.7Hz, 2H), 1.54 (ddd, J=16.3, 8.5, 7.4Hz, 2H), 1.40-1.28 (m, 4H); 13 C NMR (101 MHz, DMSO-d6) δ 170.80, 162.50, 154.37, 137.94, 130.79, 128.83, 126.40, 124.32, 107.97, 37.80, 34.22, 26.51, 26.18, 25.51. Example 29

[0053] (Z)-N-Hydroxy-6-(4-((2,3-dihydrobenzofuran-5-yl)methylene)-2,5-dioxoimidazolidin-1-yl)hexanamide: The raw materials in step 1 of Example 1 were replaced with 2-methoxybenzaldehyde and 2,3-dihydrobenzofuran-5-carboxaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was replaced with 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; a white solid was obtained with a yield of 28%. 1 H NMR (400MHz.DMSO-d6) δ10.61 (d, J=3.3Hz, 1H), 9.08 (d, J=3.5Hz, 1H), 8.88 (s, 1H), 7.40 (d t, J=2.4, 0.9Hz, 1H), 7.39 (dd, J=8.9, 2.3Hz, 1H), 7.05 (s, 1H), 6.94 (d, J=8.9Hz, 1H), 4.52 ( ddd, J=13.7, 5.1, 3.3Hz, 2H), 3.75 (t, J=6.6Hz, 2H), 3.21 (ddd, J=5.1, 3.3, 1.0Hz, 1H), 3.1 5 (ddd, J=5.1, 3.2, 1.0Hz, 1H), 2.02 (t, J=8.6Hz, 2H), 1.70-1.56 (m, 4H), 1.41-1.32 (m, 2H); 13C NMR (101 MHz, DMSO-d6) δ 170.22, 164.09, 160.24, 154.38, 130.17, 128.83, 127.44, 126.41, 125.77, 116.42, 110.54, 71.81, 38.78, 35.88, 29.73, 26.85, 26.28, 25.41. Example 30

[0054] (Z)-N-Hydroxy-6-(4-(benzofuran-5-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw material in step 1 of Example 1 was changed to 2-methoxybenzaldehyde or 1-benzofuran-5-carboxaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was changed to 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; the product was a white solid with a yield of 24%. 1 H NMR (400MHz, DMSO-d6) δ10.56 (d, J=3.3Hz, 1H), 9.06 (d, J=3.5Hz, 1H), 8.86 (s, 1H), 8.05 (d, J=1.6Hz, 1H), 7.96-7.88 (m, 1H), 7.65 (d, J=8.4Hz, 1H), 7.60 (dd, J=8.4, 2.2Hz, 1H), 6.81 (t, J=1.8Hz, 1H), 6.62 (s, 1H), 3.72 (t, J =6.6Hz, 2H), 1.96 (t, J = 8.6Hz, 2H), 1.60-1.45 (m, 4H), 1.40-1.32 (m, 2H); 13 C NMR (101 MHz, DMSO-d6) δ 169.95, 163.09, 155.98, 154.38, 145.74, 130.79, 128.96, 127.56, 125.84, 123.47, 117.25, 112.37, 106.95, 37.80, 35.85, 26.62, 26.22, 25.38. Example 31

[0055] (Z)-N-hydroxy-6-(4-(benzo[d][1,3]dioxol-5-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw material in step 1 of Example 1 was changed to 2-methoxybenzaldehyde or 3,4-methylenedioxybenzaldehyde (piperonal), and the fragment 7-bromoheptanoate in step 2 was changed to 6-bromohexanoate. The other steps and operations were the same as those in Example 1; the product was a white solid with a yield of 40%. 1H NMR (400MHz, DMSO-d6) δ10.53 (d, J=3.3Hz, 1H), 9.01 (d, J=3.5Hz, 1H), 8.77 (s, 1H), 7.12 (d, J=2.0Hz, 1H), 7.09 (dd, J=8.8, 2.0Hz, 1H) , 6.96 (d, J=8.8Hz, 1H), 6.66 (s, 1H), 6.00 (s, 2H), 3.75 (t, J=6.6Hz, 2H), 1.99 (t, J=8.6Hz, 2H), 1.69-1.50 (m, 4H), 1.41-1.32 (m, 2H); 13 C NMR (101 MHz, DMSO-d6) δ 170.12, 164.09, 154.38, 150.14, 147.86, 128.85, 125.62, 124.45, 115.35, 110.08, 109.64, 102.28, 37.80, 35.52, 26.70, 26.20, 25.52. Example 32

[0056] (Z)-N-Hydroxy-6-(4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methylene)-2,5-dioxoimidazolidin-1-yl)hexanamide, the structural formula is as follows: The raw material in step 1 of Example 1 was changed to 2-methoxybenzaldehyde or 2,2-difluoro-1,3-benzodioxole-5-carboxaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was changed to 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1; the product was a pale yellow solid with a yield of 33%. 1 H NMR (400MHz, DMSO-d6) δ10.57 (d, J=3.3Hz, 1H), 9.11 (d, J=3.5Hz, 1H), 8.78 (s, 1H), 7.24 (d, J=2.0Hz, 1H), 7.19 (d, J=8.1Hz, 1H ), 7.11 (dd, J = 8.0, 1.9 Hz, 1H), 6.66 (s, 1H), 3.72 (t, J = 6.6 Hz, 2H), 1.99 (t, J = 8.6 Hz, 2H), 1.67-1.52 (m, 4H), 1.42-1.33 (m, 2H); 13C NMR (101 MHz, DMSO-d6) δ 169.86, 164.09, 154.38, 143.72, 143.63, 143.55, 142.72, 142.63, 142.55, 134.27, 132.13, 129.98, 128.97, 125.62, 124.36, 115.49, 113.94, 113.93, 113.69, 38.80, 35.22, 26.77, 26.58, 25.01. Example 33 (Z)-N-(2-amino-4-fluorophenyl)-4-((2,5-dioxo-4-(pyridin-3-ylmethylene)imidazolidin-1-yl)methyl)benzamide, the structural formula is as follows: The raw material in step 1 in Example 1 was changed to 2-methoxybenzaldehyde or 3-pyridinecarboxaldehyde, the fragment 7-bromoheptanoic acid ethyl ester in step 2 was changed to 4-bromomethylbenzoic acid methyl ester, and the raw material hydroxylamine hydrochloride in step 4 was changed to 4-fluoro-1,2-phenylenediamine. Other steps and operations were the same as in Example 1; light yellow solid, yield: 30%. 1 H NMR (400MHz, DMSO-d6) δ9.45 (s, 1H), 8.89 (s, 1H), 8.73-8.69 (m, 1H), 8.53 (ddd, J=3.9, 1.9, 1.1Hz, 1H), 7.96-7.90 (m, 2H), 7.74 (dt, J=7.7, 1.9H z, 1H), 7.67 (dd, J=8.2, 5.0Hz, 1H), 7.41 (dt, J=8.4, 1.0Hz, 2H), 7.33 (dd, J=7.8, 3.8Hz, 1H), 6.86-6.76 (m, 2H), 6.77 (s, 1H), 4.87-4.82 (m, 4H); 13 C NMR (101 MHz, DMSO-d6) δ 173.88, 163.71, 159.89, 157.87, 153.97, 150.39, 149.90, 142.01, 141.95, 137.31, 134.82, 132.71, 130.72, 129.00, 128.44, 126.22, 126.20, 125.90, 123.64, 122.86, 122.80, 114.39, 106.69, 106.53, 102.71, 102.55, 39.76. Example 34 (Z)-N-(2-amino-4-fluorophenyl)-4-((2,5-dioxo-4-(pyridin-3-ylmethylene)imidazolidin-1-yl)methyl)benzamide, the structural formula is as follows: The raw materials in step 1 of Example 1 were changed to 2-methoxybenzaldehyde and 3-pyridinecarboxaldehyde, hydantoin was changed to 1-methylhydantoin, the fragment 7-bromoheptanoic acid ethyl ester in step 2 was changed to 4-bromomethylbenzoic acid methyl ester, and the raw material hydroxylamine hydrochloride in step 4 was changed to 4-fluoro-1,2-phenylenediamine. Other steps and operations were the same as those in Example 1; the product was a pale yellow solid with a yield of 31%. 1 H NMR (400MHz, DMSO-d6) δ9.45 (s, 1H), 8.77-8.73 (m, 1H), 8.53 (ddd, J=3.8, 1.9, 1.1Hz, 1H), 7.96-7.90 (m, 2H), 7.82 (dt, J=7.9, 1.9Hz, 1H), 7.67 (dd, J=8.2, 5.0Hz, 1H), 7.41 (dt, J=8.5, 1.0Hz, 2H), 7.33 (dd, J=7.8, 3.9Hz, 1H), 7.00 (s, 1H), 6.83 (td, J=8.1, 2.2 Hz, 1H), 6.78 (dd, J=8.0, 2.3Hz, 1H), 4.93 (t, J=1.0Hz, 2H), 4.84 (s, 2H), 3.30 (s, 2H); 13 C NMR (101 MHz, DMSO-d6) δ 173.88, 160.56, 159.89, 157.87, 154.94, 149.90, 149.87, 142.01, 141.95, 138.04, 134.62, 133.21, 132.71, 132.52, 129.00, 128.47, 126.22, 126.20, 123.63, 122.86, 122.80, 116.70, 106.69, 106.53, 102.71, 102.55, 41.30, 29.11. Example 35 The synthesis of (Z)-N-hydroxy-6-(2,5-dioxo-4-((4-(pyridin-4-yl)quinolin-6-yl)methylene)imidazolidin-1-yl)hexanamide is as follows: Step 1: Synthesis of 4-(pyridin-4-yl)quinoline-6-carboxaldehyde, the structural formula is as follows: 300 mmol of cycloisopropyl malonate (1.5 eq.) was dissolved in 20 mL of trimethyl orthoformate and added to a 100 mL three-necked flask. The atmosphere was replaced with nitrogen. The reaction temperature was raised to 110°C. After reflux reaction for 2 h, 20 mmol of the raw material methyl 4-aminobenzoate was dissolved in 20 mL of trimethyl orthoformate and carefully added to the reaction flask. After continuing the reaction for 2 h, the mixture was cooled to room temperature, concentrated and evaporated to remove the solvent, and the compound was washed with methanol and filtered to obtain a white solid. After drying, 40 mL of diphenyl ether was added, the atmosphere was replaced with nitrogen, the reaction temperature was raised to 240°C, and the mixture was stirred for 10-20 min. After cooling, 20 mL of n-hexane was added and stirred continuously. The solid was filtered and washed with n-hexane. After drying, a light yellow solid compound G (methyl 4-oxo-4,4a-dihydroquinoline-6-carboxylate, yield: 78%) was obtained. 3.3 mmol of compound G was dissolved in 10 mL of DMF, 341 μL phosphorus tribromide (1.1 eq.) was slowly added dropwise at room temperature, and the reaction was carried out under nitrogen protection for 1 h. After the reaction was completed, the reaction solution was slowly poured into 100 mL of ice-water solution (vigorously stirred throughout the process), sodium acetate was added (to neutralize the reactants of phosphorus tribromide and water), and the mixture was extracted with ethyl acetate solution (3×60 mL). The organic phase was collected and washed with saturated brine (2×200 mL), dried over anhydrous magnesium sulfate, and purified by column chromatography (PE:EA=3:1) to obtain a light yellow compound H (methyl 4-bromoquinoline-6-carboxylate, yield: 88%); 2 mmol of compound H, 3 mmol of 4-pyridineboronic acid, 0.1 mmol of Pd(dppf)Cl2 (5 mol%) and 4 mmol of potassium carbonate were added to 15 mL of In a reaction flask containing 1,4-dioxane and 3 mL of water, the reaction mixture was reacted at 80°C for 2 h under a nitrogen atmosphere. The reaction mixture was then cooled to room temperature, the solid was filtered, and the mixture was purified by column chromatography (PE:EA = 1:1) to obtain a pale yellow compound I (methyl 4-(pyridin-4-yl)quinoline-6-carboxylate, yield: 90%). 1 mmol of compound I was weighed and added to 4 mL of anhydrous THF under nitrogen. 1.6 mL of a 2.5 mol / L, 4.0 eq. solution of LiAlH4 in THF was slowly added at 0°C. The reaction temperature was raised to room temperature. After 2 h, 0.16 g of water was added to quench the reaction. The reaction mixture was stirred for 10 min, followed by the addition of 0.16 g of a 10% aqueous solution of NaOH and 0.48 g of water. The mixture was dried over anhydrous magnesium sulfate, the solid was filtered, and the mixture was concentrated to obtain a pale yellow crude compound J ((4-(pyridin-4-yl)quinolin-6-yl)methanol).1 mmol of crude compound J was dissolved in 10 mL of DCM, and 1.2 mmol of DMP (dissolved in 10 mL of DCM) was slowly added dropwise at room temperature. The reaction was allowed to react for 5 h. 20 mL of DCM was added to dilute the reaction solution, and the solution was washed with saturated aqueous sodium carbonate solution (40 mL), saturated sodium thiosulfate solution (40 mL), and saturated brine (2 x 40 mL) in sequence. The solution was dried over anhydrous magnesium sulfate and purified by column chromatography (DCM:MeOH=20:1) to give a light yellow compound K (4-(pyridin-4-yl)quinoline-6-carbaldehyde, yield: 83%). 1 H NMR (400 MHz, Chloroform-d) δ 8.71-8.64 (m, 3H), 8.52 (d, J = 4.8 Hz, 1H), 8.10 (d, J = 8.2 Hz, 1H), 8.03 (dd, J = 8.1, 2.2 Hz, 1H), 7.88-7.83 (m, 2H), 7.80 (d, J = 4.6 Hz, 1H). Step 2: Synthesis of (Z)-N-hydroxy-6-(2,5-dioxo-4-((4-(pyridin-4-yl)quinolin-6-yl)methylene)imidazolidin-1-yl)hexanamide. The structural formula is as follows: The raw material in step 1 of Example 1 was changed to 2-methoxybenzaldehyde or 4-(pyridin-4-yl)quinoline-6-carboxaldehyde, and the fragment 7-bromoheptanoic acid ethyl ester in step 2 was changed to 6-bromohexanoic acid ethyl ester. The other steps and operations were the same as those in Example 1. The yield was 40%. 1 H NMR (400MHz, DMSO-d6) δ10.53 (d, J=3.3Hz, 1H), 9.03 (d, J=3.5Hz, 1H), 8.84 (s, 1H), 8.69-8.64 (m, 2H), 8.48 (d, J = 4.8Hz, 1H), 8.33 (d, J = 2.6Hz, 1H), 8.03 (d, J = 8.2Hz, 1H ), 7.88-7.83 (m, 2H), 7.75 (d, J=4.7Hz, 1H), 7.61 (dd, J=8.2, 2.2Hz, 1H), 6.68 (s, 1H) , 3.72 (t, J=6.6Hz, 2H), 2.01 (t, J=8.6Hz, 2H), 1.68-1.53 ​​(m, 4H), 1.41-1.30 (m, 2H); 13CNMR (101 MHz, DMSO-d6) δ 169.53, 164.09, 154.38, 149.88, 149.55, 146.53, 141.95, 139.80, 132.11, 128.92, 128.87, 127.25, 126.96, 123.87, 122.06, 121.54, 115.90, 36.84, 35.10, 26.45, 26.51, 25.01. HDAC kinase inhibition assay was performed on the inhibitor of the present invention: ADP-Glo ​​Luminescent Kinase Assay was used for the kinase reaction. The reagents used in the kinase reaction were as follows: HEPES (50 mM) pH 7.5 with NaCl (100 mM), EGTA (1.0 mM), MgCl2 (3.0 mM), DTT (2.0 mM), and CHAPS (0.03%) were added. During the reaction, 50 μM PIP2 and 25 μM ATP were added to each 10 mL of test compound at different concentrations (0.05 nM-1.0 μM). The reaction system was incubated at room temperature for 1 hour, and then 10 μL of the reagent ADP-Glo ​​was added to terminate the enzyme reaction. Data were collected using Envision software, and Graphpad Prism 5 was used to analyze and fit the IC values ​​of the compounds. 50 value.

[0057] Table 1 HDAC1 enzyme inhibitory activity (IC 50 , nM) As shown in Table 1, the compounds of the present invention have nanomolar inhibitory activity against HDAC1, and some compounds are significantly better than the positive control Vorinostat. In particular, Example 11 has an inhibitory activity against HDAC1 that is nearly 30 times that of the positive control Vorinostat. This shows that the compounds of the present invention are highly effective HDAC inhibitors.

[0058] The antiproliferative activity of the inhibitor of the present invention was tested on tumor cell lines: CCK 8 method was used to evaluate the antiproliferative activity of the compound on cells, and the half inhibitory concentration IC was determined by single concentration activity screening and multiple concentration determination. 50 The assay principle is as follows: Cytotoxicity (CCK 8 assay): The CCK 8 reagent contains WST-8, which is reduced by mitochondrial dehydrogenases to a highly water-soluble yellow formazan product (formazan) under the action of the electron carrier 1-methoxy-5-methylphenazine methylsulfate (1-methoxy PMS). The amount of formazan produced is proportional to the number of viable cells.

[0059] The experimental method is as follows: (1) Cell inoculation: cells were prepared into a single cell suspension using culture medium containing 10% fetal bovine serum, and 90 μL of 5×10 cells were inoculated into each well of a 96-well plate. 4 / mL of adherent cells and 9×10 4 / mL suspension cells were pre-cultured at 5% CO2 and 37°C for 24h.

[0060] (2) Add the sample solution to be tested: add 10 μL of sample solution to each well. Set one concentration for each sample in the initial activity screening, and set up 3 replicate wells; IC 50 Eight concentrations (including 0) were measured, with three replicates for each concentration. The cells were then incubated in an incubator for 48 hours. The experiment consisted of a blank group (Blank), a control group (Control), and a drug group (Drug).

[0061] (3) Color development: Aspirate the old culture medium and drug solution from adherent cells (add 10 μL CCK 8 stock solution directly to suspended cells), add 100 μL CCK 8 solution diluted tenfold to each well, and continue to culture at 37°C, 5% CO2 for 14 h (operation, real-time observation).

[0062] (4) Detection: Measure the absorbance at 450 nm using an enzyme-labeled instrument and record the raw data results.

[0063] (5) The original data were normalized using Excel software, and the cell proliferation inhibition rate was calculated by the OD value of each well (formula = (OD Control OD Drug ) / (OD Control OD Blank )×100%), statistical inhibition rate. IC 50 Calculated by GraphPad Prism 8.

[0064] Table 2 Tumor cell line proliferation inhibitory activity (IC 50 , μM) As can be seen in Table 2, the compounds of the present invention exhibit micromolar antiproliferative activity against both tumor strains. In particular, the example compounds exhibited high sensitivity against the human prostate cancer cell line DU-145. Among them, nine compounds, including Examples 11-18 and 29, all exhibited inhibitory activity of less than 100 nanomolar against DU-145, significantly outperforming the positive control, Vorinostat. This suggests that the example compounds of the present invention have potential clinical applications in the treatment of these tumors.

[0065] The imidazolidinedione HDAC inhibitor of the present invention has high sensitivity to prostate cancer by effectively inhibiting the proliferation of solid tumor cells through HDAC, and its anti-tumor efficacy can be potentially used in its clinical treatment.

[0066] In addition to the above embodiments, the present invention may also have other implementations. Any technical solution formed by equivalent replacement or equivalent transformation falls within the scope of protection required by the present invention.

Claims

1. An imidazolidinedione HDAC inhibitor, characterized in that: The inhibitor is a substituted imidazolidinedione compound represented by the general formula V, or a stereoisomer, hydrate or pharmaceutically acceptable salt thereof, and the general formula is as follows: wherein W is selected from an oxygen atom or a sulfur atom; X, Y, Z, M1, and M2 each independently represent a carbon or nitrogen atom; when X, Y, Z, M1, and M2 are carbon atoms, each independently may be substituted by R3, and R3 is hydrogen, alkyl, cyano, halogen, haloalkyl, hydroxyl, mercapto, alkoxy, alkylthio, alkoxyalkyl, aralkyl, aryl, or Het; Q is selected from a saturated or unsaturated straight or branched hydrocarbon group having a length of 1 to 9 carbon atoms, an aryl group or Het; R1 is hydrogen, deuterium, alkyl, haloalkyl, hydroxy, mercapto, alkoxy, alkylamino, alkylthio, alkoxyalkyl, methylene, aralkyl, diarylalkyl, aryl or Het; R2 is selected from hydroxy, 2-aminophenyl optionally substituted with one or more R4; R4 is hydrogen, alkyl, cyano, halogen, haloalkyl, hydroxy, mercapto, alkoxy, alkylthio, alkoxyalkyl, aralkyl, aryl or Het; The alkyl group is a straight-chain or branched saturated hydrocarbon group having 1 to 9 carbon atoms; or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms; or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms connected to a straight-chain or branched saturated hydrocarbon group having 1 to 6 carbon atoms; Alkoxy is a straight or branched chain saturated hydrocarbon group having 1 to 9 carbon atoms; or a cyclic saturated hydrocarbon group having 3 to 9 carbon atoms; or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms connected to a straight or branched chain saturated hydrocarbon group having 1 to 9 carbon atoms; wherein each carbon atom is optionally substituted by oxygen; Alkylamino is a straight-chain or branched saturated hydrocarbon group having 1 to 9 carbon atoms; or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms; or a cyclic saturated hydrocarbon group having 3 to 6 carbon atoms connected to a straight-chain or branched saturated hydrocarbon group having 1 to 9 carbon atoms; wherein each carbon atom is optionally substituted by an NH group; Alkoxyalkyl is an alkoxy group as defined above attached to an alkyl group; Alkenyl and alkynyl are straight-chain or branched unsaturated hydrocarbon groups containing double or triple bonds and having 1 to 9 carbon atoms; Aryl is a carbocyclic ring selected from phenyl, naphthyl, acenaphthyl or tetrahydronaphthyl, each of which is optionally substituted with 1, 2 or 3 substituents, each substituent being independently selected from hydrogen, alkyl, cyano, halogen, haloalkyl, hydroxy, mercapto, alkoxy, alkylthio, alkoxyalkyl, aralkyl, diarylalkyl, aryl or Het; Aralkyl and diarylalkyl are aryl groups as defined above linked to an alkyl group; Het is a monocyclic heterocycle selected from pyrrolyl, pyrazolyl, imidazolyl, furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl; or a bicyclic heterocycle selected from quinolyl, quinoxalinyl, indolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzofuranyl, benzothienyl, 2,3-dihydrobenzo[1,4]dioxinyl or benzo[1,3]dioxolyl; or a monocyclic saturated hydrocarbon group of 3 to 6 carbon atoms, a bicyclic saturated hydrocarbon group of 6 to 12 carbon atoms, wherein the carbon atoms on the ring are independently optionally substituted by 1-4 O, S, N or NH; each monocyclic or bicyclic ring is optionally substituted by 1, 2 or 3 substituents, each substituent being independently selected from halogen, haloalkyl, hydroxy, alkyl or alkoxy; halogen is a substituent selected from fluorine, chlorine, bromine or iodine; haloalkyl is a straight or branched chain saturated hydrocarbon group having 1-9 carbon atoms, or a cyclic saturated hydrocarbon group having 3-6 carbon atoms, or a cyclic saturated hydrocarbon group having 3-6 carbon atoms connected to a straight or branched chain saturated hydrocarbon group having 1-6 carbon atoms; wherein one or more carbon atoms are substituted by one or more halogen atoms.

2. The imidazolidinedione HDAC inhibitor according to claim 1, characterized in that: In the general formula V, W is selected from an oxygen atom or a sulfur atom; X, Y, Z, M1, and M2 each independently represent a carbon or nitrogen atom; when X, Y, Z, M1, and M2 are carbon atoms, each independently may be substituted by R3, and R3 is hydrogen, alkyl, cyano, halogen, haloalkyl, alkoxy, alkylthio, or alkoxyalkyl; Q is selected from saturated or unsaturated straight or branched hydrocarbon groups, and aromatic groups having a length of 1 to 9 carbon atoms; R2 is selected from hydroxy, 2-aminophenyl optionally substituted with one or more R4; R4 is hydrogen, alkyl, cyano, halogen, haloalkyl, aryl or Het.

3. The imidazolidinedione HDAC inhibitor according to claim 1, characterized in that: In the general formula V, W is selected from an oxygen atom or a sulfur atom; X, Y, Z, M1, and M2 each independently represent a carbon or nitrogen atom; when X, Y, Z, M1, and M2 are carbon atoms, each independently may be optionally substituted by R3, and R3 is hydrogen, alkyl, halogen, or alkoxy; Q is selected from saturated or unsaturated straight or branched hydrocarbon groups or aromatic groups having a length of 3 to 9 carbon atoms; R2 is selected from hydroxy, 2-aminophenyl optionally substituted with one or more R4; R4 is hydrogen, alkyl, cyano, halogen, haloalkyl, aryl or Het.

4. The imidazolidinedione HDAC inhibitor according to claim 1, characterized in that: In the general formula V, the hydrogen bonded to the carbon is replaced by deuterium, an isotope of hydrogen.

5. The imidazolidinedione HDAC inhibitor according to claim 1, characterized in that: The inhibitor is one of the following, (1) (Z)-N-hydroxy-7-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)heptylamide; (2) (Z)-N-hydroxy-8-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)octanamide; (3) (Z)-N-hydroxy-6-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidinazole-1-yl)hexanamide; (4) (Z)-N-hydroxy-5-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)pentanamide; (5) (Z)-N-hydroxy-7-(4-(4-bromo-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)heptylamide; (6) (Z)-N-hydroxy-8-(4-(4-bromo-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)octanamide; (7) (Z)-N-hydroxy-9-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)nonanamide; (8) (Z)-N-hydroxy-10-(4-(2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)decanamide; (9) (Z)-N-hydroxy-7-(4-(2-methoxybenzylidene)-3-methyl-2,5-dioxoimidazolidin-1-yl)heptylamide; (10) (Z)-N-hydroxy-7-(4-(4-bromo-2-methoxybenzylidene)-3-methyl-2,5-dioxoimidazolidin-1-yl)heptylamide; (11) (Z)-N-hydroxy-6-(4-(4-bromo-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (12) (Z)-N-hydroxy-6-(4-(3-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (13) (Z)-N-hydroxy-6-(4-(4-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (14) (Z)-N-hydroxy-6-(4-(2,4-dimethoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (15) (Z)-N-hydroxy-6-(4-(4-fluoro-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (16) (Z)-N-hydroxy-6-(4-(4-chloro-2-methoxybenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (17) (Z)-N-hydroxy-6-(4-(2-methoxy-4-methylbenzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (18) (Z)-N-hydroxy-6-(4-(2-methoxy-4-(trifluoromethyl)benzylidene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (19) (Z)-N-Hydroxy-6-(2,5-dioxo-4-(3,4,5-trimethoxybenzylidene)imidazolidin-1-yl)hexanamide; (20) (Z)-N-hydroxy-6-(4-(naphthalen-1-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (21) (Z)-N-hydroxy-6-(4-(naphthalen-2-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (22) (Z)-N-hydroxy-6-(2,5-dioxo-4-(quinolin-2-ylmethylene)imidazolidin-1-yl)hexanamide; (23) (Z)-N-hydroxy-6-(2,5-dioxo-4-(quinolin-3-ylmethylene)imidazolidin-1-yl)hexanamide; (24) (Z)-N-hydroxy-6-(2,5-dioxo-4-(quinolin-4-ylmethylene)imidazolidin-1-yl)hexanamide; (25) (Z)-N-hydroxy-6-(2,5-dioxo-4-(quinolin-6-ylmethylene)imidazolidin-1-yl)hexanamide; (26) (Z)-N-hydroxy-6-(2,5-dioxo-4-(quinolin-5-ylmethylene)imidazolidin-1-yl)hexanamide; (27) (Z)-N-hydroxy-6-(4-(furan-2-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (28) (Z)-N-hydroxy-6-(2,5-dioxo-4-(thien-2-ylmethylene)imidazolidin-1-yl)hexanamide; (29) (Z)-N-Hydroxy-6-(4-((2,3-dihydrobenzofuran-5-yl)methylene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (30) (Z)-N-hydroxy-6-(4-(benzofuran-5-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (31) (Z)-N-hydroxy-6-(4-(benzo[d][1,3]dioxol-5-ylmethylene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (32) (Z)-N-hydroxy-6-(4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methylene)-2,5-dioxoimidazolidin-1-yl)hexanamide; (33) (Z)-N-(2-amino-4-fluorophenyl)-4-((2,5-dioxo-4-(pyridin-3-ylmethylene)imidazolidin-1-yl)methyl)benzamide; (34) (Z)-N-(2-amino-4-fluorophenyl)-4-((2,5-dioxo-4-(pyridin-3-ylmethylene)imidazolidin-1-yl)methyl)benzamide; (35) (Z)-N-Hydroxy-6-(2,5-dioxo-4-((4-(pyridin-4-yl)quinolin-6-yl)methylene)imidazolidin-1-yl)hexanamide.

6. The method for preparing the imidazolidinedione HDAC inhibitor according to claim 5, characterized in that: The method comprises the following steps: using substituted formaldehyde (A) and hydantoin or substituted hydantoin (B) as raw materials, undergoing a Knoevenagel condensation reaction under the action of β-alanine to obtain an intermediate (C); the intermediate (C) undergoing a nucleophilic substitution reaction with a bromocarboxylate to obtain a key intermediate (D); the intermediate (D) undergoing a hydrolysis reaction under acidic conditions to obtain an intermediate (E); and the intermediate (E) undergoing a condensation reaction with hydroxylamine hydrochloride to obtain the target compound (1-32). The synthetic route is as follows:

7. The method for preparing the imidazolidinedione HDAC inhibitor according to claim 5, characterized in that: Using substituted formaldehyde (A) and hydantoin or substituted hydantoin (B) as raw materials, a Knoevenagel condensation reaction occurs in the presence of alanine to obtain intermediate (C); intermediate (C) undergoes a nucleophilic substitution reaction with a bromocarboxylate to obtain a key intermediate (D); intermediate (D) undergoes a hydrolysis reaction under acidic conditions to obtain intermediate (E); intermediate (E) undergoes a condensation reaction with 4-fluoro-1,2-phenylenediamine to obtain the target compounds (33-34). The synthetic route is as follows:

8. The method for preparing the imidazolidinedione HDAC inhibitor according to claim 5, characterized in that: Compound (F) is used as a raw material and reacts with cycloisopropyl malonate to undergo Combes quinoline synthesis to obtain intermediate (G); intermediate (G) undergoes bromination reaction with phosphorus tribromide in DMF to obtain intermediate (H); intermediate (H) undergoes Suzuki coupling reaction with 4-pyridineboronic acid to obtain intermediate (I); intermediate (I) undergoes reduction reaction with lithium aluminum hydride to obtain intermediate (J); intermediate (J) is selectively oxidized to obtain key intermediate (K), and intermediate (K) undergoes four steps to obtain target compound (35). The synthetic route is as follows:

9. A pharmaceutical composition comprising the compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein: The compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof is an active ingredient.

10. Use of the compound according to any one of claims 1 to 6 in the preparation of a medicament for preventing or treating clinical disorders associated with HDACs.

11. The use of the compound according to claim 10, characterized in that: Diseases associated with HDACs include lung cancer, melanoma, liver cancer, kidney cancer, leukemia, prostate cancer, thyroid cancer, skin diseases, pancreatic cancer, ovarian cancer, testicular cancer, breast cancer, bladder cancer, gallbladder cancer, myelodysplastic syndrome, lymphoma, esophageal cancer, gastrointestinal cancer, astrocytoma, neuroblastoma, glioma, schwannoma, mesothelioma, non-insulin-dependent diabetes mellitus, and autoimmune diseases.

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