A 2,2-dimethyl-2H-chromene derivative containing a sulfonamide unit, its preparation method and application

Abstract

The present invention relates to a 2,2-dimethyl-2H-chromene derivative containing a sulfonamide unit, a preparation method thereof and an application. The compound of the present invention has the structure of the following formula (I), which has excellent inhibitory activity against plant viruses such as potato virus Y, and can be used as a drug or medicament for preventing and treating plant viral diseases such as potato virus Y disease. It has a novel structure, a simple preparation process and low production cost.

Description

Technical Field

[0001] The present invention relates to the fields of chemical engineering and pesticides, and more specifically to 2,2-dimethyl-2H-chromene derivatives containing a sulfonamide unit, a preparation method thereof, and the application of the 2,2-dimethyl-2H-chromene derivatives containing a sulfonamide unit in drugs for preventing and treating plant virus diseases such as potato virus Y disease. Background Art

[0002] Plant virus diseases are a major type of disease in agricultural production and are known as the "cancer of plants". Currently, more than 400 viruses are known to infect plants, which can infect a variety of cash crops such as wheat, corn, potato, cucumber, tomato, pepper, and tobacco, causing serious economic losses to agricultural production. The main pesticides for preventing and treating plant viruses in China include dufulin, ningnanmycin, ribavirin, lentinan, and aminooligosaccharin. However, due to their prevention and treatment effects or stability problems, they are difficult to play an important role in agricultural production. Therefore, there is an urgent need to develop new anti-plant virus agents with high efficiency, low toxicity, novel action modes, and environmental friendliness.

[0003] The 2,2-dimethyl-2H-chromene skeleton and its derivatives are widely present in many plants and microorganisms. They are important oxygen-containing heterocyclic compounds with a wide range of biological activities, such as antiviral, anti-inflammatory, antibacterial, and anticancer pharmacological activities, and are one of the most important hot lead structures in drug discovery and innovation.

[0004] In 1992, Kashman et al. (Kashman, Y.; Gustafson, K.R.; Fuller, R.W.; Cardellina, J.H.; McMahon, J.B.; Currens, M.J.; Buckheit, R.W.J.; Hughes, S.H.; Cragg, G.M.; Boyd, M.R. The calanolides, a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree Calophyllum lanigerum [J]. J. Med. Chem, 1992, 35: 2735-2743.) isolated a series of compounds Calanolide A with anti-human immunodeficiency virus (HIV) activity from the tropical rainforest tree Calophyllum lanigerum of the genus Calophyllum. Its EC 50= 0.1 μM. This natural product is a coumarin derivative containing a 2,2-dimethyl-2H-chromene structure and is one of the earliest discovered natural products with anti-HIV-1 activity, specifically acting on the NNRTIs of HIV-1. Calanolide A can not only effectively inhibit wild-type HIV-1 but also has ideal inhibitory activity against zidovudine-resistant and other clinically variant HIV-1 strains. Later, it was found that (+)-calanolide A is the active enantiomer.

[0005] In 2012, Hu Qiufen et al. (Hu, Q.F.; Zhou, B.; Gao, X.M. Antiviral chromones from the stem of Cassia siamea[J]. J. Nat. prod., 2012, 75: 1909 - 1914.) isolated 2,2-dimethyl-2H-chromene derivatives with anti-tobacco mosaic virus (TMV) activity from the stem of Cassia siamea using a 95% methanol extract. At a concentration of 20 μM, with ningnanmycin as the control agent, the anti-TMV activity of the compound was tested using the half-leaf lesion method. The test results showed that the 2,2-dimethyl-2H-chromene derivative had good anti-TMV inactivation activity (35.3%), superior to the control agent ningnanmycin (30.2%). The protective activity (42.7%) was also superior to that of the control ningnanmycin (27.4%).

[0006] In 2014, Li Yinke et al. (Li, Y.K.; Meng, Y.L.; Yang, Y.C.; Qin, L.; Xia, C.F.; Ye, Y.Q.; Gao, X.M.; Hu, Q.F. Chromones from the stems of Cassia fistula and their anti-tobacco mosaic virus activities[J]. Phytochem. Lett., 2014, 10: 46 - 49.) isolated 2,2-dimethyl-2H-chromene derivatives from the stem of Cassia siamea using a 70% acetone extract. At a concentration of 20 μM, it had good anti-TMV inactivation activity (30.8%), slightly lower than that of the control agent ningnanmycin (34.8%).

[0007] Chinese Patent No. CN103524472B was published on June 24, 2015, disclosing a phenolic compound, its preparation method and application. This phenolic compound has a 2,2-dimethyl-2H-chromene unit. Using the half-leaf lesion method, when the mass concentration of the agent was 50 mg / L, the anti-TMV activity of the compound was measured. The results showed that the relative inhibition rate of the compound was 38.5%, much higher than that of the control ningnanmycin (28.2%).

[0008] Chinese Patent No. CN104387402B disclosed a kind of isocoumarin compound, its preparation method and uses on August 31, 2016. For the first time, an isocoumarin compound with a 2,2-dimethyl-2H-chromene unit was isolated from the whole tobacco plant. Using the half-leaf method and ningnanmycin as the control agent, the anti-TMV activity of the compound was measured at a mass concentration of 50 mg / L. The results showed that the relative inhibition rate of the compound was 33.8%, which was better than that of the positive control agent ningnanmycin (31.5%).

[0009] Chinese Patent No. CN109535169B disclosed a chromone derivative, its preparation method and application on April 10, 2020. The chromone derivative contains a 2,2-dimethyl-2H-chromene structure. At a concentration of 50 mg / L, the relative inhibition rate against TMV was 38.7%, which was much higher than that of the control ningnanmycin (30.8%).

[0010] Chinese Patent No. CN109438464B disclosed a chromone derivative extracted from Cassia leschenaultiana DC. and its preparation method and application on June 16, 2020. The compound is a chromone derivative containing a 2,2-dimethyl-2H-chromene structure. At 50 mg / L, the relative inhibition rate against TMV was 35.6%, which was much higher than that of the control ningnanmycin (30.8%).

[0011] Chinese Patent No. CN115557960A disclosed a prenylated indole alkaloid compound, its preparation method and application on January 3, 2023. A new indole alkaloid compound with a 2,2-dimethyl-2H-chromene structure, named isoaspergilline A, was isolated from the fermentation products of the tobacco endogenous fungus Aspergillus versicolor YATS1111. Using the half-leaf spot method, the anti-TMV activity of the compound was measured at a mass concentration of 20 μM. Its relative inhibition rate against TMV reached 58.4%, which was significantly higher than that of the control agent ningnanmycin (33.2%).

[0012] In summary, natural drug small molecules containing 2,2-dimethyl-2H-chromene have good antiviral activity, among which natural products containing 2,2-dimethyl-2H-chromene structure are widely used to resist plant viruses. At present, chemical agents are still the main means of preventing and controlling plant viral diseases, which mainly include natural products and chemically synthesized antiviral agents. However, at this stage, highly effective, broad-spectrum and low-risk antiviral chemicals for non-target organisms are still very rare, and the current chemical synthesis and natural antiviral agents have unsatisfactory effects on the prevention and control of plant viral diseases, which seriously affects the development of agricultural production. Therefore, finding a new, efficient and low-risk anti-plant viral agent is still a key issue and major challenge facing the field of plant protection. Summary of the invention

[0013] One of the purposes of the present invention is to provide a class of 2,2-dimethyl-2H-chromene derivatives containing sulfonamide units and a preparation method thereof.

[0014] Another object of the present invention is to provide a composition containing the above compound.

[0015] Another object of the present invention is to provide the use of the above compound or the composition.

[0016] Another object of the present invention is to provide a method for controlling agricultural pests and diseases using the above compounds or the composition.

[0017] To achieve the above object, the present invention adopts the following technical solutions:

[0018] The 2,2-dimethyl-2H-chromene derivative containing a sulfonamide unit of the present invention has the following general structural formula (I):

[0019]

[0020] Where:

[0021] R 1 is independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, amino, thiol, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted cycloalkyl or optionally substituted or unsubstituted aryl;

[0022] R 2 is independently selected from one or more of hydrogen, deuterium, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl or optionally substituted heteroaryl;

[0023] R 3independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, amino, mercapto, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted cycloalkyl or optionally substituted or unsubstituted aryl;

[0024] R 4 independently selected from one or more of optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted heteroaryl or optionally substituted or unsubstituted benzyl.

[0025] Preferably:

[0026] said R 1 independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, cyano, amino, mercapto, carboxyl, C1-C6 alkyl, C1-C6 alkenyl, substituted or unsubstituted C6-C 15 aryl or substituted or unsubstituted C3-C6 heteroaryl;

[0027] said R 2 independently selected from one or more of hydrogen, deuterium or C1-C6 alkenyl;

[0028] said R 3 independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, cyano, amino, mercapto, carboxyl, C1-C6 alkyl, C1-C6 alkenyl, substituted or unsubstituted C6-C 15 aryl or substituted or unsubstituted C3-C6 heteroaryl;

[0029] said R 4 independently selected from substituted or unsubstituted C1-C 12 alkyl, substituted or unsubstituted C1-C6 alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted C6-C 15 aryl or substituted or unsubstituted C3-C6 heteroaryl;

[0030] Said substitution means being optionally substituted by one or more of halogen, nitro, hydroxyl, cyano, amino, mercapto, carboxyl or C1-C6 alkyl.

[0031] More preferably:

[0032] said R 1 independently selected from one or more of hydrogen, deuterium, halogen, nitro, hydroxyl, cyano, amino, mercapto, carboxyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, phenyl, benzyl or pyridyl;

[0033] said R 2independently selected from hydrogen, deuterium or 3-methyl-2-butenyl;

[0034] said R 3 independently selected from hydrogen, deuterium, halogen, nitro, hydroxy, cyano, amino, mercapto, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, phenyl, benzyl or pyridyl;

[0035] said R 4 independently selected from hydrogen, deuterium, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, n-pentyl, isopentyl, hexyl, heptyl, octyl, cyclopropyl, cyclohexyl, morpholinyl, phenyl, benzyl, pyridyl, pyrazolyl, pyrrolyl, furyl, thienyl, thiazolyl, benzopyrrolyl, pyridazine, pyrimidine, pyrazine, vinyl, amino, methylamino, dimethylamino, ethylamino 、 -CH2CH2CN, -CHCNCH3, -CH2CH2CH2CN, -CH2CHCNCH3, -CHCNCH2CH3, -CH2CH2F, -CHFCH3, -CH2CH2CH2F, -CH2CHFCH3, -CHFCH2CH3, -CH2CH2Cl, -CHClCH3, -CH2CH2CH2Cl, -CH2CHClCH3, -CHClCH2CH3, -CH2CH2Br, -CHBrCH3, -CH2CH2CH2Br, -CH2CHBrCH3, -CHBrCH2CH3,

[0036] Further preferred compounds are the following compounds I1 - I25:

[0037] Compound I1: (E)-4-methoxy-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0038] Compound I2: (E)-4-(trifluoromethyl)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0039] Compound I3: (E)-N-(4-((((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)octane-1-sulfonamide;

[0040] Compound I4: (E)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)thiophene-2-sulfonamide;

[0041] Compound I5: (E)-4-Fluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0042] Compound I6: (E)-4-Chloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0043] Compound I7: (E)-3-Fluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0044] Compound I8: (E)-2-Fluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0045] Compound I9: (E)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)pyridine-3-sulfonamide;

[0046] Compound I10: (E)-4-Methyl-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0047] Compound I11: (E)-3-Cyano-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0048] Compound I12: (E)-4-Nitro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0049] Compound I13: (E)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)cyclopropanesulfonamide;

[0050] Compound I14: (E)-2,5-Dichloro-N-(4-(((5-hydroxy-2,2-chromen-2H-methoxy-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0051] Compound I15: (E)-2,5-Difluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0052] Compound Ⅰ16: (E)-3-bromo-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0053] Compound Ⅰ17: (E)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0054] Compound Ⅰ18: (E)-4-ethyl-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0055] Compound Ⅰ19: (E)-2,4,6-trimethyl-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0056] Compound Ⅰ20: (E)-4-(tert-butyl)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromene)methylene)amino)phenyl)benzenesulfonamide;

[0057] Compound Ⅰ21: (E)-N-(4-(N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)sulfamoyl)phenyl)acetamide;

[0058] Compound Ⅰ22: (E)-2-(trifluoromethyl)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0059] Compound Ⅰ23: (E)-3,5-dichloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide;

[0060] Compound Ⅰ24: (E)-5-chloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)thiophene-2-sulfonamide;

[0061] Compound Ⅰ25: (E)-2-chloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide.

[0062] The present invention also provides a preparation method of 2,2-dimethyl-2H-chromene compounds containing a sulfonamide unit, and the synthesis route is as follows:

[0063]

[0064] Most preferably, it specifically includes:

[0065]

[0066] The present invention also provides a 2,2-dimethyl-2H-chromene compound containing a sulfonamide unit.

[0067] The present invention also provides a composition, which contains the 2,2-dimethyl-2H-chromene compound containing a sulfonamide unit or its stereoisomer, and an agriculturally acceptable adjuvant or fungicide, insecticide or herbicide; preferably, the dosage form of the composition is selected from emulsifiable concentrate (EC), dust (DP), wettable powder (WP), granule (GR), aqueous solution (AS), suspension concentrate (SC), ultra-low volume spray (ULV), soluble powder (SP), microcapsule (MC), smoke agent (FU), emulsion in water (EW), water dispersible granule (WG).

[0068] The present invention also provides the use of a 2,2-dimethyl-2H-chromene compound containing a sulfonamide unit, or the composition in the prevention and control of agricultural pests and diseases.

[0069] Preferably: the agricultural pests and diseases are plant virus diseases.

[0070] More preferably: the agricultural pests and diseases are Potato virus Y.

[0071] The present invention also provides a method for preventing and controlling agricultural pests and diseases, by applying the 2,2-dimethyl-2H-chromene compound containing a sulfonamide unit, or the composition to agricultural pests and diseases.

[0072] Preferably: the agricultural pests and diseases are plant virus diseases.

[0073] More preferably, the agricultural pests and diseases are Potato virus Y.

[0074] As used herein, "alkyl" includes branched and straight-chain saturated hydrocarbon groups having a specific number of carbon atoms. For example, "C 1-10 alkyl" (or alkylene) is intended to mean C1, C2, C3, C4, C5, C6, C7, C8, C9 and C 10 alkyl. Additionally, for example, "C 1-6 alkyl" represents an alkyl group having 1 to 6 carbon atoms. The alkyl group can be unsubstituted or substituted such that one or more of its hydrogen atoms are replaced by other chemical groups. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl (such as n-propyl and isopropyl), butyl (such as n-butyl, isobutyl, tert-butyl), pentyl (such as n-pentyl, isopentyl, neopentyl) and the like.

[0075] The "alkenyl" includes both straight-chain or branched-chain hydrocarbons and has one or more carbon-carbon double bonds at any stable point in the chain. For example, "C 2-6 alkenyl" (or alkenylene) is intended to include C2, C3, C4, C5, and C6 alkenyls. Examples of alkenyls include, but are not limited to, vinyl, 1-propenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, 4-methyl-3-pentenyl, and the like.

[0076] The "cycloalkyl" refers to cycloalkyls and includes mono-, bi-, or polycyclic systems. C 3-7 cycloalkyl is intended to include C3, C4, C5, C6, and C7 cycloalkyls. Examples of cycloalkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl, and the like. As used herein, "carbocyclic ring" or "carbocyclic residue" refers to any stable 3-, 4-, 5-, 6-, or 7-membered monocyclic or bicyclic ring or 7-, 8-, 9-, 10-, 11-, 12-, or 13-membered bicyclic or tricyclic ring, which may be saturated, partially unsaturated, unsaturated, or aromatic. Examples of these carbocyclic rings include, but are not limited to, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, pentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, adamantyl, cyclooctyl, cyclooctenyl, cyclooctadiene, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane, [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, anthryl, and tetrahydronaphthyl (tetralin). As described above, bridged rings are also included in the definition of carbocyclic rings (such as [2.2.2]bicyclooctane). Unless otherwise specified, preferred carbocyclic rings are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. When the term "carbocyclic ring" is used, it is intended to include "aryl". When one or more carbon atoms connect two non-adjacent carbon atoms, bridged rings occur. Preferred bridges are one or two carbon atoms. It is noted that the bridge always converts a monocyclic ring into a bicyclic ring. When the ring is bridged, the substituents of the ring are also present on the bridge.

[0077] The "aryl" refers to a monocyclic or bicyclic aromatic hydrocarbon group having 6 to 12 carbon atoms in the ring portion, such as phenyl and naphthyl, each of which may be substituted.

[0078] The "halogen" or "halogen atom" refers to fluorine, chlorine, bromine, and iodine.

[0079] The term "heteroaryl" refers to substituted and unsubstituted aromatic 5- or 6-membered monocyclic groups, 9- or 10-membered bicyclic groups, and 11- to 14-membered tricyclic groups, having at least one heteroatom (O, S or N) in at least one ring, and the heteroatom-containing ring preferably has 1, 2 or 3 heteroatoms selected from O, S and N. Each ring of the heteroaryl containing heteroatoms may contain one or two oxygen or sulfur atoms and / or consist of 1 to 4 nitrogen atoms, provided that the total number of heteroatoms in each ring is 4 or less and each ring has at least one carbon atom. The fused rings completing the bicyclic and tricyclic groups may contain only carbon atoms and may be saturated, partially saturated or unsaturated. The nitrogen and sulfur atoms may be optionally oxidized and the nitrogen atoms may be optionally quaternized. The bicyclic or tricyclic heteroaryl must include at least one fully aromatic ring, but the other fused rings may be aromatic or non-aromatic. The heteroaryl may be attached to any available nitrogen or carbon atom of any ring. When the valence allows, if the other ring is a cycloalkyl or heterocycle, it is additionally optionally substituted with =O (oxygen). Description of the Drawings

[0080] Appendix Figure 1 It is the anti-PVY activity result of compound I10 and ningnanmycin at a concentration of 500 μg / mL;

[0081] Appendix Figure 2 It is the inactivation activity of compound I10 and ningnanmycin against PVY at various concentrations. Detailed Description of the Invention

[0082] The present invention will be further described below by way of examples. It should be understood that the methods described in the embodiments of the present invention are only used to illustrate the present invention, rather than limiting the present invention. Any simple improvement of the preparation method of the present invention under the premise of the concept of the present invention belongs to the scope protected by the present invention. All raw materials and solvents used in the examples are commercially available reagents of corresponding purity.

[0083] Example 1: Synthesis of (E)-4-methoxy-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide (Ⅰ1):

[0084] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0085] At room temperature, 3-methyl-2-butenal (10.3 mL, 103.6 mmol), CaCl2 (6.32 g, 43.0 mmol), and triethylamine (24.0 mL, 172.1 mmol) were added to a solution of 2,4-dihydroxybenzaldehyde (7.15 g, 51.8 mmol) in ethanol (172 mL). The mixture was refluxed for 2 h. The reaction was monitored by thin-layer chromatography. After the raw materials were completely reacted, the reaction mixture was cooled and acidified with 2N HCl. The addition was stopped when the pH reached 6. The reaction mixture was extracted with ethyl acetate, and the organic phase was washed with saturated brine. The organic layers were combined, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the target compound 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde, 5.83 g of yellow solid, with a yield of 55%. 1 HNMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H, -OH), 9.80 (s, 1H, -CHO), 7.55 (d, J = 8.6 Hz, 1H, Ar-H), 6.60 (d, J = 10.1 Hz, 1H, Ar-H), 6.48 (d, J = 8.5 Hz, Ar-H), 5.78 (d, J = 10.1 Hz, Ar-H), 1.41 (s, 6H, -CH3). 13 CNMR (101 MHz, DMSO-d6) δ 195.5, 160.0, 157.7, 135.1, 129.8, 115.9, 115.0, 109.5, 108.7, 78.4, 28.3.

[0086] (2) Synthesis of (N-(4-aminophenyl)-4-methoxybenzenesulfonamide):

[0087] p-Phenylenediamine (300 mg, 2.77 mmol) was dissolved in 15 mL of dichloromethane, and triethylamine (280 mg, 2.77 mmol) was added. 4-Methoxybenzenesulfonyl chloride (573 mg, 2.77 mmol) was dissolved in 5 mL of dichloromethane and added dropwise to the above solution under an ice bath. The ice bath was removed, and the reaction was carried out at room temperature. The reaction was monitored by thin-layer chromatography. After the raw materials were completely reacted, dichloromethane was removed under negative pressure. 20 mL of water was added, and the mixture was stirred on a magnetic stirrer for 1 h. The resulting solid was filtered and dried to obtain the intermediate (N-(4-aminophenyl)-4-methoxybenzenesulfonamide. The obtained intermediate could be used in the next reaction without purification.

[0088] (3) Synthesis of (E)-4-methoxy-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide):

[0089] Dissolve 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde (150 mg, 0.73 mmol) and N-(4-aminophenyl)-4-methoxybenzenesulfonamide (204 mg, 0.73 mmol) in 20 mL of anhydrous ethanol, add a catalytic amount of glacial acetic acid, heat under reflux, monitor the reaction by thin-layer chromatography. When the raw materials are completely reacted, cool to room temperature, pour the system into ice water, add an appropriate amount of saturated brine, stir and let stand. Filter the precipitated yellow solid by suction, recrystallize with methanol, and dry to obtain 206 mg of yellow solid with a yield of 60.38%.

[0090] Example 2: Synthesis of (E)-4-(trifluoromethyl)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide (I2):

[0091] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0092] Synthesized according to the method and conditions of Example 1(1);

[0093] (2) Synthesis of (N-(4-aminophenyl)-4-trifluoromethylbenzenesulfonamide:

[0094] Synthesized according to the method and conditions of Example 1(2), with the difference that 4-trifluoromethylbenzenesulfonyl chloride is used as the raw material;

[0095] (3) Synthesis of (E)-4-(trifluoromethyl)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0096] Synthesized according to the method and conditions of Example 1(3), with the difference that (N-(4-aminophenyl)-4-trifluoromethylbenzenesulfonamide is used as the raw material;

[0097] Example 3: Synthesis of (E)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)octane-1-sulfonamide (I3):

[0098] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0099] Synthesized according to the method and conditions of Example 1(1);

[0100] (2) Synthesis of N-(4-aminophenyl)octane-1-sulfonamide:

[0101] Synthesized according to the method and conditions of Example 1(2), with the difference that octane-1-sulfonyl chloride is used as the raw material;

[0102] (3)(E)-Synthesis of N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)octane-1-sulfonamide:

[0103] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)octane-1-sulfonamide was used as the raw material;

[0104] Example 4: Synthesis of (E)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)thiophene-2-sulfonamide (Ⅰ4):

[0105] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0106] Synthesized according to the method and conditions of Example 1(1);

[0107] (2) Synthesis of N-(4-aminophenyl)thiophene-2-sulfonamide:

[0108] Synthesized according to the method and conditions of Example 1(2), with the difference that thiophene-2-sulfonyl chloride was used as the raw material;

[0109] (3) Synthesis of (E)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)thiophene-2-sulfonamide:

[0110] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)thiophene-2-sulfonamide was used as the raw material;

[0111] Example 5: Synthesis of (E)-4-fluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide (Ⅰ5):

[0112] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0113] Synthesized according to the method and conditions of Example 1(1);

[0114] (2) Synthesis of N-(4-aminophenyl)-4-fluorobenzenesulfonamide:

[0115] Synthesized according to the method and conditions of Example 1(2), with the difference that 4-fluorobenzenesulfonyl chloride was used as the raw material;

[0116] (4) Synthesis of (E)-4-fluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0117] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-4-fluorobenzenesulfonamide is used as the raw material;

[0118] Example 6: Synthesis of (E)-4-chloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide (Ⅰ6):

[0119] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0120] Synthesized according to the method and conditions of Example 1(1);

[0121] (2) Synthesis of N-(4-aminophenyl)-4-chlorobenzenesulfonamide:

[0122] Synthesized according to the method and conditions of Example 1(2), with the difference that 4-chlorobenzenesulfonyl chloride is used as the raw material;

[0123] (3) Synthesis of (E)-4-chloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0124] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-4-chlorobenzenesulfonamide is used as the raw material;

[0125] Example 7: Synthesis of (E)-3-fluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide (Ⅰ7):

[0126] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0127] Synthesized according to the method and conditions of Example 1(1);

[0128] (2) Synthesis of N-(4-aminophenyl)-3-fluorobenzenesulfonamide:

[0129] Synthesized according to the method and conditions of Example 1(2), with the difference that 3-fluorobenzenesulfonyl chloride is used as the raw material;

[0130] (3) Synthesis of (E)-3-fluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0131] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-3-fluorobenzenesulfonamide is used as the raw material;

[0132] Example 8: Synthesis of (E)-2-fluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide (I8):

[0133] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0134] Synthesized according to the method and conditions of Example 1(1);

[0135] (2) Synthesis of N-(4-aminophenyl)-2-fluorobenzenesulfonamide:

[0136] Synthesized according to the method and conditions of Example 1(2), with the difference that 2-fluorobenzenesulfonyl chloride is used as the raw material;

[0137] (3) Synthesis of (E)-2-fluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0138] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-2-fluorobenzenesulfonamide is used as the raw material;

[0139] Example 9: Synthesis of (E)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)pyridine-3-sulfonamide (I9):

[0140] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0141] Synthesized according to the method and conditions of Example 1(1);

[0142] (2) Synthesis of N-(4-aminophenyl)pyridine-3-sulfonamide:

[0143] Synthesized according to the method and conditions of Example 1(2), with the difference that pyridine-3-sulfonyl chloride is used as the raw material;

[0144] (3) Synthesis of (E)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)pyridine-3-sulfonamide:

[0145] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)pyridine-3-sulfonamide is used as the raw material;

[0146] Example 10: Synthesis of (E)-4-methyl-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide (I10):

[0147] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0148] Synthesized according to the method and conditions of Example 1(1);

[0149] (2) Synthesis of N-(4-aminophenyl)-4-methylbenzenesulfonamide:

[0150] Synthesized according to the method and conditions of Example 1(2), with the difference that 4-methylbenzenesulfonyl chloride is used as the raw material;

[0151] (3) Synthesis of (E)-4-methyl-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromene-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0152] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-4-methylbenzenesulfonamide is used as the raw material;

[0153] Example 11: Synthesis of (E)-3-cyano-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromene-6-yl)methylene)amino)phenyl)benzenesulfonamide (I11):

[0154] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0155] Synthesized according to the method and conditions of Example 1(1);

[0156] (2) Synthesis of N-(4-aminophenyl)-3-cyanobenzenesulfonamide:

[0157] Synthesized according to the method and conditions of Example 1(2), with the difference that 3-cyanobenzenesulfonyl chloride is used as the raw material;

[0158] (3) Synthesis of (E)-3-cyano-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromene-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0159] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-3-cyanobenzenesulfonamide is used as the raw material;

[0160] Example 12: Synthesis of (E)-4-nitro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromene-6-yl)methylene)amino)phenyl)benzenesulfonamide (Ⅰ12):

[0161] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0162] Synthesized according to the method and conditions of Example 1(1);

[0163] (2) Synthesis of N-(4-aminophenyl)-4-nitrobenzenesulfonamide:

[0164] Synthesized according to the method and conditions of Example 1(2), with the difference that 4-nitrobenzenesulfonyl chloride was used as the raw material;

[0165] (3) Synthesis of (E)-4-nitro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0166] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-4-nitrobenzenesulfonamide was used as the raw material;

[0167] Example 13: Synthesis of (E)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)cyclopropanesulfonamide (Ⅰ13):

[0168] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0169] Synthesized according to the method and conditions of Example 1(1);

[0170] (2) Synthesis of N-(4-aminophenyl)cyclopropanesulfonamide:

[0171] Synthesized according to the method and conditions of Example 1(2), with the difference that cyclopropanesulfonyl chloride was used as the raw material;

[0172] (3) Synthesis of (E)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)cyclopropanesulfonamide:

[0173] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)cyclopropanesulfonamide was used as the raw material;

[0174] Example 14: Synthesis of (E)-2,5-dichloro-N-(4-(((5-hydroxy-2,2-chromene-2H-methoxy-6-yl)methylene)amino)phenyl)benzenesulfonamide (Ⅰ14):

[0175] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0176] Synthesized according to the method and conditions of Example 1(1);

[0177] (2) Synthesis of N-(4-aminophenyl)-2,5-dichlorobenzenesulfonamide:

[0178] Synthesized by the method and conditions of Example 1(2), with the difference that 2,5-dichlorobenzenesulfonyl chloride is used as the raw material;

[0179] (3) Synthesis of (E)-2,5-dichloro-N-(4-(((5-hydroxy-2,2-chromene-2H-methoxy-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0180] Synthesized by the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-2,5-dichlorobenzenesulfonamide is used as the raw material;

[0181] Example 15: Synthesis of (E)-2,5-difluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromene-6-yl)methylene)amino)phenyl)benzenesulfonamide (Ⅰ15):

[0182] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0183] Synthesized by the method and conditions of Example 1(1);

[0184] (2) Synthesis of N-(4-aminophenyl)-2,5-difluorobenzenesulfonamide:

[0185] Synthesized by the method and conditions of Example 1(2), with the difference that 2,5-difluorobenzenesulfonyl chloride is used as the raw material;

[0186] (3) Synthesis of (E)-2,5-difluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromene-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0187] Synthesized by the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-2,5-difluorobenzenesulfonamide is used as the raw material;

[0188] Example 16: Synthesis of (E)-3-bromo-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromene-6-yl)methylene)amino)phenyl)benzenesulfonamide (Ⅰ16):

[0189] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0190] Synthesized by the method and conditions of Example 1(1);

[0191] (2) Synthesis of N-(4-aminophenyl)-3-bromobenzenesulfonamide:

[0192] Synthesized by the method and conditions of Example 1(2), with the difference that 3-bromobenzenesulfonyl chloride is used as the raw material;

[0193] (3) Synthesis of (E)-3-bromo-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0194] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-3-bromobenzenesulfonamide was used as the raw material;

[0195] Example 17: Synthesis of (E)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide (Ⅰ17):

[0196] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0197] Synthesized according to the method and conditions of Example 1(1);

[0198] (2) Synthesis of N-(4-aminophenyl)benzenesulfonamide:

[0199] Synthesized according to the method and conditions of Example 1(2), with the difference that benzenesulfonyl chloride was used as the raw material;

[0200] (3) Synthesis of (E)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0201] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)benzenesulfonamide was used as the raw material;

[0202] Example 18: Synthesis of (E)-4-ethyl-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide (Ⅰ18):

[0203] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0204] Synthesized according to the method and conditions of Example 1(1);

[0205] (2) Synthesis of N-(4-aminophenyl)-4-ethylbenzenesulfonamide:

[0206] Synthesized according to the method and conditions of Example 1(2), with the difference that 4-ethylbenzenesulfonyl chloride was used as the raw material;

[0207] (3) Synthesis of (E)-4-ethyl-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0208] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-4-ethylbenzenesulfonamide is used as the raw material;

[0209] Example 19: Synthesis of (E)-2,4,6-trimethyl-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide (Ⅰ19):

[0210] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0211] Synthesized according to the method and conditions of Example 1(1);

[0212] (2) Synthesis of N-(4-aminophenyl)-2,4,6-trimethylbenzenesulfonamide:

[0213] Synthesized according to the method and conditions of Example 1(2), with the difference that 2,4,6-trimethylbenzenesulfonyl chloride is used as the raw material;

[0214] (3) Synthesis of (E)-2,4,6-trimethyl-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0215] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-2,4,6-trimethylbenzenesulfonamide is used as the raw material;

[0216] Example 20: Synthesis of (E)-4-(tert-butyl)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromene)methylene)amino)phenyl)benzenesulfonamide (Compound No. Ⅰ20):

[0217] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0218] Synthesized according to the method and conditions of Example 1(1);

[0219] (2) Synthesis of N-(4-aminophenyl)-4-tert-butylbenzenesulfonamide:

[0220] Synthesized according to the method and conditions of Example 1(2), with the difference that 4-tert-butylbenzenesulfonyl chloride is used as the raw material;

[0221] (3) Synthesis of (E)-4-(tert-butyl)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromene)methylene)amino)phenyl)benzenesulfonamide:

[0222] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-4-tert-butylbenzenesulfonamide is used as the raw material;

[0223] Example 21: Synthesis of (E)-N-(4-(N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)sulfamoyl)phenyl)acetamide (I21):

[0224] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0225] Synthesized according to the method and conditions of Example 1(1);

[0226] (2) Synthesis of N-(4-(N-(4-aminophenyl)sulfamoyl)phenyl)acetamide:

[0227] Synthesized according to the method and conditions of Example 1(2), with the difference that 4-acetamidobenzenesulfonyl chloride is used as the raw material;

[0228] (3) Synthesis of (E)-N-(4-(N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)sulfamoyl)phenyl)

[0229] acetamide:

[0230] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-(N-(4-aminophenyl)sulfamoyl)phenyl)acetamide is used as the raw material;

[0231] Example 22: Synthesis of (E)-2-(trifluoromethyl)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide (I22):

[0232] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0233] Synthesized according to the method and conditions of Example 1(1);

[0234] (2) Synthesis of N-(4-aminophenyl)-2-(trifluoromethyl)benzenesulfonamide:

[0235] Synthesized according to the method and conditions of Example 1(2), with the difference that 2-(trifluoromethyl)benzenesulfonyl chloride is used as the raw material;

[0236] (3) Synthesis of (E)-2-(trifluoromethyl)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0237] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-2-(trifluoromethyl)benzenesulfonamide is used as the raw material;

[0238] Example 23: Synthesis of (E)-3,5-dichloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide (I23), which comprises the following steps:

[0239] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0240] Synthesized according to the method and conditions of Example 1(1);

[0241] (2) Synthesis of N-(4-aminophenyl)-3,5-dichlorobenzenesulfonamide:

[0242] Synthesized according to the method and conditions of Example 1(2), with the difference that 3,5-dichlorobenzenesulfonyl chloride is used as the raw material;

[0243] (3) Synthesis of (E)-3,5-dichloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0244] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-3,5-dichlorobenzenesulfonamide is used as the raw material;

[0245] Example 24: Synthesis of (E)-5-chloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)thiophene-2-sulfonamide (I24):

[0246] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0247] Synthesized according to the method and conditions of Example 1(1);

[0248] (2) Synthesis of N-(4-aminophenyl)-5-chlorothiophene-2-sulfonamide:

[0249] Synthesized according to the method and conditions of Example 1(2), with the difference that 5-chlorothiophene-2-sulfonyl chloride is used as the raw material;

[0250] (3) Synthesis of (E)-5-chloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)thiophene-2-sulfonamide:

[0251] Synthesized according to the method and conditions of Example 1(3), with the difference that N-(4-aminophenyl)-5-chlorothiophene-2-sulfonamide is used as the raw material;

[0252] Example 25: Synthesis of (E)-2-chloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide (I25):

[0253] (1) Synthesis of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde:

[0254] Synthesized according to the method and conditions of Example 1(1);

[0255] (2) Synthesis of N-(4-aminophenyl)-2-chlorobenzenesulfonamide:

[0256] Synthesized according to the method and conditions of Example 1(2), except that 2-chlorobenzenesulfonyl chloride was used as the raw material;

[0257] (3) Synthesis of (E)-2-chloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide:

[0258] Synthesized according to the method and conditions of Example 1(3), except that N-(4-aminophenyl)-2-chlorobenzenesulfonamide was used as the raw material.

[0259] The physicochemical properties of the 2,2-dimethyl-2H-chromene derivatives containing sulfonamide units prepared in the above examples are shown in Table 1, and their structural formulas, nuclear magnetic resonance hydrogen spectra ( 1 H NMR), carbon spectra ( 13 C NMR) and high-resolution mass spectrometry (HRMS) data are shown in Table 2.

[0260] Table 1 Physicochemical properties of the target compounds in the examples

[0261]

[0262]

[0263] Table 2 Structural formulas and spectral data of the target compounds in the examples

[0264]

[0265]

[0266]

[0267]

[0268]

[0269]

[0270] Test Example 1, Anti-PVY Therapeutic and Protective Activities of Target Compounds

[0271] (1) Test Method

[0272] A. Virus Purification

[0273] Using the method of Zhou Xueping (Zhou Xueping, Xu Zhixin, Xu Jing, Li Debao. Study on Cucumber Mosaic Virus Infecting Luffa cylindrica [J]. Journal of South China Agricultural University, 1995, 16(2): 74-79.), select the upper leaves of Nicotiana tabacum.L plants infected with PVY systemically for more than 3 weeks, homogenize them in phosphate buffer, filter through double-layer gauze, centrifuge at 8000g, treat with polyethylene glycol twice, and then centrifuge again. Suspend the precipitate in phosphate buffer to obtain the purified PVY liquid. The whole experiment is carried out at 4°C. Measure the absorbance value at a wavelength of 260 nm with an ultraviolet spectrophotometer, and calculate the virus concentration according to the formula.

[0274] Virus concentration (mg / mL) = (A 260 × dilution factor) / E 0.1％ 1cm 260nm .

[0275] Where E represents the extinction coefficient, that is, the light absorption value of a suspension with a concentration of 0.1% (1 mg / mL) at a wavelength of 260 nm and a light path of 1 cm. The E of PVY 0.1％ 1cm 260nm is 5.0.

[0276] B. In Vivo Therapeutic Effect of Agent on PVY Infection

[0277] In vivo therapeutic effect of agent on infection: Select Chenopodium amaranticolor at the 5-6 leaf stage with consistent growth, top it, sprinkle carborundum evenly on the whole leaf, dip a writing brush in the virus solution (6×10 -3 mg / mL) and inoculate the virus on the whole leaf. After natural drying, rinse it with clean water. After the leaf is dry, gently apply the agent on the left half leaf with a writing brush, and apply the solvent with the corresponding solvent concentration on the right half leaf as a control. Record the number of necrotic spots after 4-5 days, and calculate the inhibition rate according to the following formula.

[0278] C. In Vivo Protective Effect of Agent on PVY Infection

[0279] In vivo protective effect of agent on infection: Select Chenopodium amaranticolor at the 5-6 leaf stage with consistent growth, gently apply the agent on the left half leaf with a writing brush, and apply the solvent with the corresponding solvent concentration on the right half leaf as a control. After 24 hours, sprinkle carborundum evenly on the whole leaf, dip a writing brush in the virus solution (6×10 -3 mg / mL) and inoculate the virus on the whole leaf, rinse it with clean water, record the number of necrotic spots after 4-5 days, and calculate the inhibition rate according to the following formula:

[0280] D. In vivo inactivation effect of the agent on PVY infection

[0281] In vivo inactivation effect of the agent on PVY infection: Select Chenopodium amaranticolor at the 5-6 leaf stage with consistent growth, top it, evenly sprinkle carborundum on the whole leaf, dip a writing brush in the virus solution (6×10 -3 mg / mL) to inoculate the virus on the left half leaf, and inoculate the right half leaf with the mixture of the virus and the test compound after reacting for 30 min. After natural drying, rinse the leaf with clear water. Record the number of necrotic spots after 4-5 d, and calculate the inhibition rate according to the following formula:

[0282]

[0283] Among them, the average number of necrotic spots on the half leaf without applying the agent and the number of necrotic spots on the half leaf with the applied agent are both the averages of three replicates for each group.

[0284] Table 3 Anti-Potato virus Y treatment, protection and inactivation activities of the target compounds at a concentration of 500 μg / mL

[0285]

[0286] Using the half leaf necrotic spot method, at a concentration of 500 μg / mL, with ningnanmycin as the control agent, the anti-PVY activities of 2,2-dimethyl-2H-chromene derivatives containing a sulfonamide unit were tested. From the bioassay results in Table 3, it can be seen that most of the target compounds showed certain anti-PVY activities. The treatment and protection activities of Compounds I2, I5, I6, I7, I8, I10, I16, I17, I18, I24 and I25 were better than those of the control agent ningnanmycin. Among them, the treatment and protection activities of Compounds I7 (73.78%, 70.23%) and I10 (68.79%, 70.12%) were significantly higher than those of the control agent ningnanmycin (50.13%, 50.72%); among them, the inactivation activities of I6, I10 and I18 (80.05%, 84.10% and 79.11%) were comparable to those of the control agent ningnanmycin (82.59%).

[0287] To further study the anti-PVY activities of 2,2-dimethyl-2H-chromene derivatives containing a sulfonamide unit, we determined the EC 50 values of the inactivation activities of I6, I7, I10, I17 and I18 with good treatment, protection and inactivation activities in this type of compound. From the results in Table 4, it can be seen that the EC 50 values of the inactivation activities of Compounds I6 and I10 were 56.76 μg / mL and 53.33 μg / mL respectively, which were better than those of the control agent ningnanmycin (75.73 μg / mL); The primary screening activities and inactivation activities at each concentration of Compound I10 are shown in Figure 1 、Figure 2 .

[0288] Table 4 Inactivation activity of target compounds against Potato virus Y and inactivation EC 50 value

[0289]

[0290] As mentioned above, it is only the preferred embodiment of the present invention, and there is no limitation to the present invention in any form. Any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A 2,2-dimethyl-2H-chromene derivative containing a sulfonamide unit, characterized in that, Selected from the following specific compounds: Compound I1: (E)-4-methoxy-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide; Compound I2: (E)-4-(trifluoromethyl)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide; Compound I5: (E)-4-fluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide; Compound I6: (E)-4-chloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide; Compound I7: (E)-3-fluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide; Compound I8: (E)-2-fluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide; Compound I10: (E)-4-methyl-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide; Compound I15: (E)-2,5-difluoro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide; Compound I16: (E)-3-bromo-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide; Compound I17: (E)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide; Compound I18: (E)-4-ethyl-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide; Compound I22: (E)-2-(trifluoromethyl)-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide; Compound I24: (E)-5-chloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)thiophene-2-sulfonamide; Compound I25: (E)-2-chloro-N-(4-(((5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)methylene)amino)phenyl)benzenesulfonamide.

2. The 2,2-dimethyl-2H-chromene compound containing a sulfonamide unit according to claim 1, characterized in that, The synthetic route of the 2,2-dimethyl-2H-chromene compounds containing a sulfonamide unit is as follows: Among them, R 1 -R 3 is H, R 4 is selected from: 4-OCH3-Ph, 4-CF3-Ph, 4-F-Ph, 4-Cl-Ph, 3-F-Ph, 2-F-Ph, 4-CH3-Ph, 2,5-di-F-Ph, 3-Br-Ph, Ph, 4-CH2CH3-Ph, 2-CF3-Ph, 5-Cl-Thiophene, 2-Cl-Ph.

3. A composition, characterized in that: Containing the compound according to claim 1, and an agriculturally acceptable adjuvant or fungicide, insecticide or herbicide; the dosage form of the composition is selected from emulsifiable concentrate, powder, granule, aqueous solution, suspending agent, ultra-low volume spray, microcapsule, smoke agent, emulsion in water.

4. A composition according to claim 3, characterized in that: The powder is selected from wettable powder and soluble powder; the granule is selected from water dispersible granule.

5. Use of the compound according to claim 1 in the preparation of an agent for preventing and treating potato virus Y disease.

6. Use of the composition according to claim 3 in the preparation of an agent for preventing and treating potato virus Y disease.

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