Preparation method and medical application of visible light promoted seleno-sulfamide

Abstract

The invention relates to the technical field of organic synthetic chemistry, in particular to a preparation method and medical application of visible light promoted seleno-sulfamide. The preparation method of the seleno-sulfamide comprises the following steps: by taking (N-aryl)-alkynyl sulfamide and diselenide as reaction raw materials, carrying out stirring reaction under a certain temperature condition and light source irradiation to obtain the seleno-sulfamide compound. The synthesis method is mild in condition, does not need a metal catalyst and an oxidizing agent, and accords with the idea of green chemistry. The method also has the advantages of simple operation, high yield, high purity and the like. In-vitro cell viability tests show that the seleno-sulfamide disclosed by the invention has excellent anti-tumor activity and low toxic and side effects, can be prepared into anti-tumor drugs to be applied to clinical anti-tumor treatment, and has important significance in research of anti-tumor active drugs.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthetic chemistry, and particularly relates to a preparation method and medical use of selenium-based sultam under visible light promotion. Background Art

[0002] Sulfonamide compounds, as an important class of organic molecules, have extensive application values in the fields of drug research and development, functional materials, and synthetic chemistry. Among them, sulfonamide derivatives with a cyclic structure (sultam) are common in natural products and pharmacologically active molecular structures due to their unique molecular configurations. In view of this, developing efficient methods for synthesizing such skeletons has long attracted great attention from organic chemists and medicinal chemists.

[0003] On the other hand, selenium, as an essential trace element for the human body, plays a key role in antioxidant defense systems such as glutathione peroxidase. In recent years, the pharmacological activity research of selenium-containing compounds has become a hot topic, and experimental results show that selenium-containing compounds have good therapeutic effects on prostate cancer, breast cancer, and lung cancer. In the field of chemical synthesis, organoselenium compounds are important synthetic intermediates and catalysts, and can be used to synthesize various organic compounds such as drugs, dyes, and pesticides.

[0004] The construction of the structural diversity of selenium-containing heterocyclic skeletons not only provides a rich molecular library for the discovery of drug lead compounds, but also has important application values for systematically carrying out structure-activity relationship research and innovative drug development; in view of the unique structural skeleton of sultam and the extensive biological activities of selenium-containing compounds, developing new and efficient synthetic strategies to construct selenium-based sultam has always been the goal that synthetic chemists and medicinal chemists strive to achieve. Currently, there are mainly two strategies for the synthesis of sultam. One is the molecular cycloaddition reaction of (o-vinyl-N-phenyl)-allyl sulfonamide; the other is the cyclization reaction of 2-nitrochalcone with elemental sulfur under redox-neutral conditions. However, there is a lack of a general method for introducing selenium functional groups onto the sultam skeleton. Summary of the Invention

[0005] The present invention provides a preparation method and medical use of selenium-based sultam under visible light promotion. One of the purposes of the present invention is to provide a class of selenium-based sultam derivatives with anti-tumor activity; the second purpose of the present invention is to provide a method for preparing and purifying the above selenium-based sultam; the third purpose of the present invention is to apply the above selenium-based sultam derivatives to the preparation of clinical anti-tumor drugs.

[0006] The above objects of the present invention are achieved by the following technical solutions:

[0007] In an organic solvent, using the (N-aryl)-alkynylsulfonamide with the structure shown in formula (I) and the diselenide with the structure shown in formula (II) as reaction raw materials, under visible light irradiation, stir the reaction open to the air at room temperature. After the reaction is completed, remove the solvent from the reaction solution under reduced pressure to obtain a crude product, and purify the crude product by column chromatography to obtain the seleno inner sulfonamide compound with the structure shown in formula (III); the reaction equation is shown as follows:

[0008]

[0009] Among them, the compound of formula (I) is (N-aryl)-alkynylsulfonamide, and the substituent R 1 is furyl, thienyl, pyridyl, naphthyl, phenyl, phenyl substituted by one or more substituents, where the substituents are alkoxy, alkyl, halogen, trifluoromethoxy; the substituent R 2 is C 1 -C 10 alkyl, 3-6 carbon cycloalkyl, naphthyl, furyl, phenyl, phenyl with one substituent, where the substituents are halogen, alkyl, alkylamino, alkoxy, cyano; the substituent R 3 is phenyl, carbonyl, halogen or pivaloyl.

[0010] The compound of formula (II) is diaryl diselenide or dialkyl diselenide.

[0011] The molar ratio of the (N-aryl)-alkynylsulfonamide with the structure shown in formula (I) to the diselenide with the structure shown in formula (II) is 1:0.5 - 1:1, preferably 1:0.5.

[0012] The organic solvent is acetonitrile, chloroform, carbon tetrachloride, chlorobenzene, nitromethane, preferably nitromethane.

[0013] The irradiation light source for the reaction is one of sunlight, white fluorescent lamp, blue LED, purple LED lamp, preferably blue LED.

[0014] Preferably, the reaction is carried out at room temperature for 20 h - 30 h.

[0015] After the reaction is completed, concentrate the reaction solution under reduced pressure, separate the concentrate by column chromatography, using a mixed solution of petroleum ether and ethyl acetate as the eluent, where the volume ratio of petroleum ether to ethyl acetate is (1 - 20):1, collect the eluate, and obtain the seleno inner sulfonamide compound with the structure shown in formula (III) after rotary evaporation of the solvent.

[0016] The seleno inner sulfonamide derivative prepared by the present invention has excellent anti-tumor performance and can be preferably applied to the preparation of drugs for treating anti-tumor diseases. Among them, the therapeutic effects on tumor diseases such as liver cancer, gastric cancer, colon cancer, breast cancer and lung cancer are particularly significant.

[0017] Furthermore, the selenium-based internal sulfonamide derivative or its pharmaceutically acceptable salt, solvate and hydrate obtained by the present invention can be combined with a pharmaceutically acceptable carrier or diluent to form a pharmaceutical preparation. Pharmaceutically acceptable carriers include inert solid fillers or diluents and sterile aqueous or organic solutions.

[0018] The beneficial effects of the present invention are as follows:

[0019] (1) The conditions of the present invention are mild. Harsh reaction conditions are not required during the synthesis process, reducing energy consumption and equipment requirements. At the same time, it has good compatibility with various functional groups.

[0020] (2) The present invention does not require the use of metal catalysts and photocatalysts, avoiding the pollution of the product by metal residues and the potential harm to the environment, which conforms to the environmental protection concept of green chemistry.

[0021] (3) Experiments have proved that the selenium-based internal sulfonamide derivatives provided by the present invention selectively have a strong inhibitory effect on the proliferation of various tumor cells (including liver cancer, gastric cancer, colon cancer, breast cancer, lung cancer, etc.), while causing less damage to normal cells. Therefore, the compounds of the present invention have important prospects for medical use. Detailed implementation manners

[0022] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0023] The present invention provides the following technical solution: In an organic solvent, (N-aryl)-alkynyl sulfonamide with the structure shown in formula (I) and diselenide with the structure shown in formula (II) are used as reaction raw materials. Under visible light irradiation, the reaction is stirred open to the air. After the reaction is completed, the solvent in the reaction solution is removed under reduced pressure to obtain a crude product, and the crude product is purified by column chromatography to obtain a selenium-based internal sulfonamide compound with the structure shown in formula (III); the reaction equation is shown as follows:

[0024]

[0025] Among them, the compound of formula (I) is (N-aryl)-alkynyl sulfonamide, and the substituent R 1 is furyl, thienyl, pyridyl, naphthyl, phenyl, phenyl substituted by one or more substituents, and the substituents are alkoxy, alkyl, halogen, trifluoromethoxy; the substituent R 2is a C1-C10 alkyl group, a 3-6 carbon cycloalkyl group, a naphthyl group, a furyl group, a phenyl group, or a phenyl group with one substituent, where the substituent is a halogen, an alkyl group, an alkylamino group, an alkoxy group, or a cyano group; substituent R 3 is a phenyl group, a carbonyl group, a halogen, or a pivaloyl group.

[0026] The compound of formula (II) is a diaryl diselenide or a dialkyl diselenide.

[0027] The compound of formula (I) is prepared by the following route:

[0028]

[0029] Example 1

[0030] The reaction equation is shown as follows:

[0031]

[0032] Charge N-methyl-N,2-diphenylethynyl-1-sulfonamide (0.2 mmol), diphenyl diselenide (0.1 mmol), and nitromethane (2 mL) into a 20 mL test tube equipped with a magnetic stir bar. After adding, place a blue LED lamp 2 cm away from the test tube and react at room temperature for 30 hours under open conditions. After the reaction is completed, remove the solvent from the organic phase using a rotary evaporator, and purify the residue using a silica gel column (the silica gel specification is 200 mesh - 300 mesh, and the eluent is petroleum ether / ethyl acetate = 6 / 1) to obtain the target compound with a yield of 78%. 1 H NMR (400 MHz, CDCl 3 ): δ 7.40 (d, J = 9.2 Hz, 5H), 7.22 (d, J = 17.2 Hz, 5H), 7.19 (d, J = 5.0 Hz, 2H), 7.01–6.94 (m, 2H), 3.60 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 153.0, 140.2, 138.0, 132.5, 131.7, 131.0, 130.6, 129.0, 129.6, 128.6, 128.5, 127.6, 124.0, 122.9, 120.5, 116.4, 32.5.

[0033] Example 2

[0034] The reaction equation is shown as follows:

[0035]

[0036] Into a 20 mL test tube equipped with a magnetic stir bar, N-methyl-N,2-diphenylethynyl-1-sulfonamide (0.2 mmol), diphenyldiselenide (0.1 mmol) and acetonitrile (2 mL) were added. After addition, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 h under open conditions. After the reaction was completed, the organic phase was concentrated by rotary evaporation, and the residue was purified by silica gel column chromatography (silica gel specification: 200 mesh - 300 mesh, eluent: petroleum ether / ethyl acetate = 6 / 1) to obtain the target compound with a yield of 71%.

[0037] Example 3

[0038] The reaction equation is shown as follows:

[0039]

[0040] Into a 20 mL test tube equipped with a magnetic stir bar, N-methyl-N,2-diphenylethynyl-1-sulfonamide (0.2 mmol), diphenyldiselenide (0.1 mmol) and carbon tetrachloride (2 mL) were added. After addition, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 h under open conditions. After the reaction was completed, the organic phase was concentrated by rotary evaporation, and the residue was purified by silica gel column chromatography (silica gel specification: 200 mesh - 300 mesh, eluent: petroleum ether / ethyl acetate = 6 / 1) to obtain the target compound with a yield of 67%.

[0041] Example 4

[0042] The reaction equation is shown as follows:

[0043]

[0044] Into a 20 mL test tube equipped with a magnetic stir bar, 2-(4-(tert-butyl)phenyl)-N-methyl-N-phenylethynyl-1-sulfonamide (0.2 mmol), diphenyldiselenide (0.1 mmol) and nitromethane (2 mL) were added. After addition, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 h under open conditions. After the reaction was completed, the organic phase was concentrated by rotary evaporation, and the residue was purified by silica gel column chromatography (silica gel specification: 200 mesh - 300 mesh, eluent: petroleum ether / ethyl acetate = 5 / 1) to obtain the target compound with a yield of 78%. 1 H NMR(400MHz,CDCl 3 ):δ7.50–7.38(m,5H),7.30–7.14(m,4H),7.11–7.03(m,4H),3.54(s,3H),1.33(s,9H). 13 C NMR(100MHz,CDCl 3): δ 152.9, 152.0, 141.1, 134.3, 132.2, 131.7, 131.3, 130.4, 128.8, 129.3, 127.9, 124.8, 124.5, 124.0, 122.3, 116.2, 35.1, 32.4, 31.3。

[0045] Example 5

[0046] The reaction equation is shown as follows:

[0047] Charge 2-(4-(cyano)phenyl)-N-methyl-N-phenylethynyl-1-sulfonamide (0.2 mmol), diphenyldiselenide (0.1 mmol) and nitromethane (2 mL) into a 20 mL test tube equipped with a magnetic stir bar. After adding, place a blue LED lamp 2 cm away from the test tube and react at room temperature for 30 hours under open conditions. After the reaction is completed, remove the solvent from the organic phase by a rotary evaporator, and purify the residue by a silica gel column (the silica gel specification is 200 mesh - 300 mesh, and the eluent is petroleum ether / ethyl acetate = 6 / 1) to obtain the target compound with a yield of 70%. 1 H NMR (400 MHz, CDCl 3 ): δ 7.75–7.62 (m, 2H), 7.55 (m, 1H), 7.39–7.41 (m, 2H), 7.23 (s, 1H), 7.30–7.21 (m, 5H), 7.10–7.06 (m, 1H), 6.91 (dd, J = 8.1, 1.4 Hz, 1H), 3.58 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 151.5, 141.8, 141.1, 132.3, 132.4, 132.3, 130.5, 130.4, 129.7, 127.8, 125.6, 123.5, 122.7, 118.0, 117.4, 112.8, 32.5。

[0048] Example 6

[0049] The reaction equation is shown as follows:

[0050]

[0051] Into a 20 mL test tube equipped with a magnetic stir bar, N-methyl-2-(1-naphthyl)-N-phenylethynyl-1-sulfonamide (0.2 mmol), diphenyldiselenide (0.1 mmol) and nitromethane (2 mL) were added. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was concentrated by rotary evaporation to remove the solvent, and the residue was purified by silica gel column chromatography (silica gel specification: 200 mesh - 300 mesh, eluent: petroleum ether / ethyl acetate = 4 / 1) to obtain the target compound with a yield of 85%. 1 H NMR(400MHz,CDCl 3 ):δ7.95(t,J=7.2Hz,2H),7.69(d,J=7.7Hz,1H),7.58–7.50(m,2H),7.49–7.45(m,1H),7.55–7.48(m,1H),7.40–7.41(m,2H),7.24–7.29(m,1H),7.22–7.18(m,4H),7.08–7.00(m,2H),3.58(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ139.0,138.3,135.1,133.5,129.7,130.2,128.8,129.3,128.3,128.7,128.0,127.7,128.2,126.5,126.3,125.2,124.7,40.6.

[0052] Example 7

[0053] The reaction equation is as follows:

[0054]

[0055] Into a 20 mL test tube equipped with a magnetic stir bar, N-methyl-N-phenyl-2-(2-thienyl) (0.2 mmol), diphenyldiselenide (0.1 mmol) and nitromethane (2 mL) were added. After addition, a blue LED light was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was concentrated by rotary evaporation to remove the solvent, and the residue was purified by silica gel column chromatography (silica gel specification: 200 mesh - 300 mesh, eluent: petroleum ether / ethyl acetate = 5 / 1) to obtain the target compound with a yield of 82%. 1 H NMR(400MHz,CDCl 3): δ 7.52–7.40 (m, 14 2H), 7.47–7.40 (m, 2H), 7.25–7.23 (m, 1H), 7.21–7.18 (m, 4H), 7.10–7.06 (m, 2H), 6.96 (d, J = 3.5 Hz, 1H), 3.51 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 148.2, 140.4, 137.1, 131.8, 130.4, 129.3, 129.6, 129.1, 122.3, 122.0, 120.5, 116.9, 30.4.

[0056] Example 8

[0057] The reaction equation is shown as follows:

[0058]

[0059] Charge N-(3,5-dimethylphenyl)-N-methyl-2-phenylethynyl-1-sulfonamide (0.2 mmol), diphenyldiselenide (0.1 mmol) and nitromethane (2 mL) into a 20 mL test tube equipped with a magnetic stir bar. After adding, place a blue LED lamp 2 cm away from the test tube and react at room temperature for 30 hours under open conditions. After the reaction is completed, remove the solvent from the organic phase by a rotary evaporator, and purify the residue by a silica gel column (the silica gel specification is 200 mesh - 300 mesh, and the eluent is petroleum ether / ethyl acetate = 5 / 1) to obtain the target compound with a yield of 85%. 1 H NMR (400 MHz, CDCl 3 ): δ 7.50–7.46 (m, 2H), 7.42–7.33 (m, 3H), 7.20–7.16 (m, 3H), 7.19 (dd, J = 8.0, 1.4 Hz, 2H), 7.01 (s, 1H), 6.81 (s, 1H), 3.42 (s, 3H), 2.34 (s, 3H), 1.58 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 153.8, 141.2, 140.8, 139.9, 131.0, 130.7, 130.3, 129.5, 128.7, 128.3, 128.4, 127.7, 124.3, 123.5, 116.4, 33.5, 22.9, 22.0.

[0060] Example 9

[0061] The reaction equation is shown as follows:

[0062]

[0063] Into a 20 mL test tube equipped with a magnetic stir bar, N-methyl-2-phenyl-N-(4-neopentanoylphenyl) (0.2 mmol), diphenyldiselenide (0.1 mmol) and nitromethane (2 mL) were charged. After addition, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 h under open conditions. After the reaction was completed, the organic phase was concentrated by rotary evaporation to remove the solvent, and the residue was purified by silica gel column chromatography (silica gel specification: 200 mesh - 300 mesh, eluent: petroleum ether / ethyl acetate = 4 / 1) to obtain the target compound with a yield of 81%. 1 H NMR(400MHz,CDCl 3 ):δ8.10–7.89(m,1H),7.63–7.50(m,1H),7.50(d,J=5.3Hz,4H),7.29–7.23(m,2H),7.30–7.14(m,4H),7.13–7.11(m,1H),4.19(t,J=7.3Hz,1H),3.58(s,3H),2.78–2.65(m,1H),2.05–1.80(m,1H),1.82–1.63(m,1H),1.41–1.18(m,2H),1.01–0.80(m,3H). 13 C NMR(100MHz,CDCl 3 ):δ194.5,153.2,144.1,137.3,137.2,133.3,133.4,132.6,131.9,130.8,130.3,129.9,128.8,129.4,128.6,128.8,129.9,127.3,125.2,123.5,116.0,45.6,33.4,32.2,21.5,14.2.

[0064] Example 10

[0065] The reaction equation is shown as follows:

[0066]

[0067] Into a 20 mL test tube equipped with a magnetic stir bar, N-([1,1'-biphenyl]-4-yl)-N-methyl-2-phenylethynyl-1-sulfonamide (0.2 mmol), diphenyldiselenide (0.1 mmol) and nitromethane (2 mL) were added. After adding, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was concentrated by rotary evaporation, and the residue was purified by silica gel column chromatography (silica gel specification: 200 mesh - 300 mesh, eluent: petroleum ether / ethyl acetate = 7 / 1) to obtain the target compound with a yield of 86%. 1 H NMR(400MHz,CDCl 3 ):δ7.73(dd,J=8.5,2.0Hz,1H),7.52–7.43(m,5H),7.33–7.26(m,6H),7.27–7.13(m,6H),3.66(s,3H)。 13 CNMR(100MHz,CDCl 3 ):δ153.5,140.3,140.0,137.9,136.3,133.1,130.3,130.7,129.7,128.8,129.5,129.3,128.6,128.4,127.4,126.7,125.1,124.8,116.8,32.6。

[0068] Example 11

[0069] The reaction equation is shown as follows:

[0070]

[0071] Into a 20 mL test tube equipped with a magnetic stir bar, N,N,2-triphenylethynyl-1-sulfonamide (0.2 mmol), diphenyldiselenide (0.1 mmol) and nitromethane (2 mL) were added. After adding, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was concentrated by rotary evaporation, and the residue was purified by silica gel column chromatography (silica gel specification: 200 mesh - 300 mesh, eluent: petroleum ether / ethyl acetate = 3 / 1) to obtain the target compound with a yield of 78%. 1 H NMR(400MHz,CDCl 3 ):δ7.56–7.37(m,10H),7.33(d,J=1.7Hz,1H),7.20–7.17(m,5H),7.10–7.05(m,2H),6.90(d,J=8.2Hz,1H)。 13 C NMR(100MHz,CDCl 3): δ 133.2, 131.3, 130.6, 130.2, 129.1, 129.6, 128.8, 128.4, 127.9, 127.6, 123.3, 121.1。

[0072] Example 12

[0073] The reaction equation is shown as follows:

[0074]

[0075] Charge N-methyl-N,2-diphenylethynyl-1-sulfonamide (0.2 mmol), dimethyldiselenide (0.1 mmol) and nitromethane (2 mL) into a 20-mL test tube equipped with a magnetic stir bar. After adding, place a blue LED lamp 2 cm away from the test tube and react at room temperature for 30 hours under open conditions. After the reaction is completed, remove the solvent from the organic phase through a rotary evaporator, and purify the residue with a silica gel column (the silica gel specification is 200 mesh - 300 mesh, and the eluent is petroleum ether / ethyl acetate = 6 / 1) to obtain the target compound with a yield of 85%. 1 H NMR (400 MHz, CDCl 3 ): δ 7.48–7.46 (m, 4H), 7.32–7.23 (m, 3H), 7.10–7.01 (m, 1H), 6.94 (dd, J = 8.0, 1.5 Hz, 1H), 3.57 (s, 3H), 2.38 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 150.5, 139.8, 138.5, 131.3, 130.5, 128.7, 128.9, 128.3, 124.6, 123.6, 122.4, 116.9, 31.6, 11.1。

[0076] Example 13

[0077] The reaction equation is shown as follows:

[0078]

[0079] Charge N-methyl-N,2-diphenylethynyl-1-sulfonamide (0.2 mmol), 1,2-bis(4-nitrophenyl)diselenide (0.1 mmol) and nitromethane (2 mL) into a 20-mL test tube equipped with a magnetic stir bar. After adding, place a blue LED lamp 2 cm away from the test tube and react at room temperature for 30 hours under open conditions. After the reaction is completed, remove the solvent from the organic phase through a rotary evaporator, and purify the residue with a silica gel column (the silica gel specification is 200 mesh - 300 mesh, and the eluent is petroleum ether / ethyl acetate = 5 / 1) to obtain the target compound with a yield of 79%.1 H NMR (400 MHz, CDCl 3 ): δ 8.12 (d, J = 8.5 Hz, 2H), 7.63–7.48 (m, 3H), 7.51–7.34 (m, 3H), 7.32 (d, J = 8.2 Hz, 1H), 7.19 (d, J = 7.0 Hz, 2H), 7.12 (t, J = 7.6 Hz, 1H), 7.00 (d, J = 6.6 Hz, 1H), 3.65 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 151.0, 139.5, 138.8, 130.9, 130.2, 129.2, 129.3, 128.6, 124.2, 123.9, 122.8, 117.4, 31.9, 10.8

[0080] Example 14

[0081] The reaction equation is shown as follows:

[0082]

[0083] N-Methyl-N,2-diphenylethynyl-1-sulfonamide (0.2 mmol), 1,2-bis(4-chlorophenyl) diselenide (0.1 mmol) and nitromethane (2 mL) were charged into a 20 mL test tube equipped with a magnetic stir bar. After adding, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 30 hours under open conditions. After the reaction was completed, the organic phase was removed by a rotary evaporator, and the residue was purified by a silica gel column (the silica gel specification was 200 mesh - 300 mesh, and the eluent was petroleum ether / ethyl acetate = 4 / 1) to obtain the target compound with a yield of 81%. 1 H NMR (400 MHz, CDCl 3 ): δ 7.51–7.39 (m, 4H), 7.43–7.29 (m, 2H), 7.29–7.17 (m, 1H), 7.23–7.12 (m, 2H), 7.20–7.15 (m, 2H), 7.11–7.01 (m, 2H), 3.63 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 153.7, 141.1, 137.3, 133.8, 134.5, 131.4, 131.3, 128.9, 129.6, 129.2, 128.1, 128.0, 123.7, 124.2, 122.6, 116.2, 32.6.

[0084] In vitro anti-tumor activity study of Example 15

[0085] The in vitro proliferation inhibitory activities of the target compounds 1a - 1l against three human tumor cells, namely HGC - 27, HepG2, HCT - 116, and human normal liver cells LO 2 were detected by the MTT method. The detailed test results are shown in the following table:

[0086]

[0087] ND:Not detected

[0088] The test results indicate that most of the compounds of the present invention have significant anti - cell proliferation activities, and are superior to the control drug fluorouracil (5 - FU). In particular, the anti - proliferation activity IC 50 values of compounds 1g, 1i, and 1l against the three tumor cells are all in single digits.

[0089] Although the embodiments of the present invention have been shown and described, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a selenosulfonamide promoted by visible light, characterized in that: The preparation method is as follows: in an organic solvent, (N-aryl)-alkynyl sulfonamide and diselenide are reacted under visible light irradiation with open stirring to obtain a selenoyl endsulfonamide compound, and the reaction equation is as shown below: Among them, R 1 is furanyl, thienyl, pyridyl, naphthyl, phenyl, or phenyl substituted with one or more substituents, wherein the substituent is alkoxy, alkyl, halogen, or trifluoromethoxy; R 2 C1-C 10 Alkyl, 3-6 carbon ring alkyl, naphthyl, furanyl, phenyl, phenyl with one substituent, wherein the substituent is halogen, alkyl, alkyl nitrogen, alkoxy, cyano; R 3 is phenyl, carbonyl, halogen or pivaloyl; R 4 is an aryl group or an alkyl group.

2. The method for preparing the visible light-promoted selenoyl lactone according to claim 1, characterized in that: The molar ratio of the (N-aryl)-alkynyl sulfonamide of the structure shown in formula (I) to the diselenide of the structure shown in formula (II) is 1:0.5-1:

1.

3. The method for preparing the visible light-promoted selenosulfonamide according to claim 1, characterized in that: The molar ratio of the p-(N-aryl)-alkynyl sulfonamide of the structure shown in formula (I) to the diselenide of the structure shown in formula (II) is 1:0.

5.

4. The method for preparing the visible light-promoted selenosulfonamide according to claim 1, characterized in that: The organic solvent is nitromethane, acetonitrile, chloroform, carbon tetrachloride or chlorobenzene.

5. The method for preparing the visible light-promoted selenoyl lactone according to claim 1, characterized in that: The irradiation light source of the visible light reaction is one of sunlight, white fluorescent lamp, blue LED and purple LED lamp; the open stirring reaction is carried out at room temperature for 20h-30h.

6. The method for preparing the visible light-promoted selenosulfonamide according to claim 1, characterized in that: After stirring for reaction, the mixture is concentrated under reduced pressure and separated by column chromatography; a mixed solution of petroleum ether and ethyl acetate is used as an eluent, wherein the volume ratio of petroleum ether to ethyl acetate is 1 to 20:

1.

7. A pharmaceutical composition, characterized in that The pharmaceutical composition comprises the selenosulfonamide compound prepared according to the method of claim 1, a medically acceptable salt, solvate or hydrate thereof, and a pharmaceutically acceptable carrier or excipient.

8. Use of the pharmaceutical composition according to claim 7, characterized in that: The pharmaceutical composition is used for preparing medicine for treating and / or preventing malignant tumors.

9. The use of the pharmaceutical composition according to claim 8, characterized in that: The malignant tumor is one of liver cancer, stomach cancer, colon cancer, breast cancer and lung cancer.

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