A method for preparing visible light-promoted seleno-based internal sulfonamides and medical uses thereof

Abstract

The present application relates to the technical field of organic synthesis chemistry, and particularly relates to a visible light promoted preparation method and medical use of seleno internal sulfonamide. The preparation method of seleno internal sulfonamide comprises the following steps: taking (N-aryl)-alkynyl sulfonamide and diselenide as reaction raw materials, and stirring under certain temperature conditions and light source irradiation to obtain seleno internal sulfonamide compound. The synthesis method is mild, does not need to use metal catalyst and oxidant, and conforms to the concept of green chemistry. The present application also has the advantages of simple operation, high yield and high purity. In vitro cell activity test shows that the seleno internal sulfonamide has excellent antitumor activity and low toxic side effects, can be prepared into an antitumor drug for clinical antitumor treatment, and has important significance for the research of antitumor active drugs.

Description

Technical Field

[0001] This invention relates to the field of organic synthetic chemistry, specifically to a method for preparing a visible light-promoted selenium-based sulfonamide and its pharmaceutical applications. Background Technology

[0002] Sulfonamides, as an important class of organic molecules, have wide applications in drug development, functional materials, and synthetic chemistry. Among them, sulfonamide derivatives with cyclic structures (sulfonamides) are commonly found in natural products and pharmacologically active molecular structures due to their unique molecular configurations. Therefore, developing efficient methods for synthesizing these skeletons has long been a focus of attention for organic chemists and medicinal chemists.

[0003] On the other hand, selenium, as an essential trace element for the human body, plays a crucial role in antioxidant defense systems such as glutathione peroxidase. In recent years, research on the pharmacological activity of selenium-containing compounds has become a hot topic, with experimental results showing that these 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 structural diversity of selenium-containing heterocyclic skeletons not only provides a rich molecular library for drug lead compound discovery but also has significant application value for systematic structure-activity relationship studies and innovative drug development. Given the unique structural skeleton of sulfonamides and the broad bioactivity of selenium-containing compounds, developing novel and efficient synthetic strategies to construct selenium-containing sulfonamides has always been a goal pursued by synthetic chemists and medicinal chemists. Currently, there are two main strategies for the synthesis of sulfonamides: one is through the cycloaddition reaction of (o-vinyl-N-phenyl)-allylsulfonamides; the other is through the cyclization reaction of 2-nitrochalcone with elemental sulfur under redox neutral conditions. However, a universal method for introducing selenium functional groups onto the sulfonamide skeleton is lacking. Summary of the Invention

[0005] This invention provides a method for preparing a visible light-promoted selenyl sulfonamide and its pharmaceutical applications. One objective of this invention is to provide a class of selenyl sulfonamide derivatives with antitumor activity. Another objective is to provide a method for preparing and purifying the above-mentioned selenyl sulfonamide. A third objective is to apply the above-mentioned selenyl sulfonamide derivatives to the preparation of clinical antitumor drugs.

[0006] The above-mentioned objective of the present invention is achieved through the following technical solution:

[0007] In an organic solvent, using (N-aryl)-alkynylsulfonamide of formula (I) and diselenyl ether of formula (II) as reactants, the reaction was carried out under visible light irradiation and with open stirring at room temperature. After the reaction was completed, the solvent was removed from the reaction solution under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain a selenium-based sulfonamide compound of formula (III). The reaction equation is shown below:

[0008]

[0009] Among them, compound (I) is (N-aryl)-alkynylsulfonamide, with substituent R 1 It is a phenyl group substituted with furanyl, thiophene, pyridyl, naphthyl, phenyl, or one or more substituents, wherein the substituent is alkoxy, alkyl, halogen, or trifluoromethoxy; substituent R 2 For C1-C 10 Alkyl, 3-6 carbocyclic alkyl, naphthyl, furanyl, phenyl, or phenyl with one substituent, wherein the substituent is halogen, alkyl, alkazyl, alkoxy, or cyano; substituent R 3 It can be phenyl, carbonyl, halogen, or neopentanoyl.

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

[0011] The molar ratio of (N-aryl)-alkynyl sulfonamide of formula (I) to diselenide of formula (II) is 1:0.5-1:1, preferably 1:0.5.

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

[0013] The light source for the reaction is one of sunlight, white fluorescent lamp, blue LED, or purple LED, with blue LED being preferred.

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

[0015] After the reaction was completed, the reaction solution was concentrated under reduced pressure, and the concentrate was separated by column chromatography using a mixture of petroleum ether and ethyl acetate as the eluent, wherein the volume ratio of petroleum ether to ethyl acetate was (1-20):1. The eluent was collected, and the solvent was evaporated by rotary evaporation to obtain the selenium-based sulfonamide compound shown in formula (III).

[0016] The selenium-based sulfonamide derivatives prepared by this invention have excellent anti-tumor properties and can be well applied to the preparation of drugs for 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 selenyl sulfonamide derivatives obtained by this invention, or their pharmaceutically acceptable salts, solvates, and hydrates, can be used in combination with pharmaceutically acceptable carriers or diluents to form pharmaceutical formulations. Pharmaceutically acceptable carriers include inert solid fillers or diluents and sterile aqueous or organic solutions.

[0018] The beneficial effects of this invention are:

[0019] (1) The present invention has mild conditions and does not require harsh reaction conditions during the synthesis process, which reduces energy consumption and equipment requirements, while having good compatibility with various functional groups.

[0020] (2) This invention does not require the use of metal catalysts and photocatalysts, thus avoiding the pollution of products by metal residues and potential harm to the environment, which is in line with the environmental protection concept of green chemistry.

[0021] (3) Experiments have shown that the selenium-based sulfonamide derivatives provided by this invention have a strong inhibitory effect on the proliferation of various tumor cells (including liver cancer, gastric cancer, colon cancer, breast cancer, and lung cancer), while causing less damage to normal cells. Therefore, the compounds of this invention have important potential for pharmaceutical applications. Detailed Implementation

[0022] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0023] This invention provides the following technical solution: In an organic solvent, using (N-aryl)-alkynylsulfonamide with the structure shown in formula (I) and diselenyl ether with the structure shown in formula (II) as reactants, the reaction is carried out under open stirring under visible light irradiation. After the reaction is completed, the solvent is removed from the reaction solution under reduced pressure to obtain a crude product. The crude product is purified by column chromatography to obtain a selenium-based sulfonamide compound with the structure shown in formula (III). The reaction equation is shown below:

[0024]

[0025] Among them, compound (I) is (N-aryl)-alkynylsulfonamide, with substituent R 1 The phenyl group is furanyl, thiophene, pyridyl, naphthyl, phenyl, or a phenyl group substituted with one or more substituents, wherein the substituents are alkoxy, alkyl, halogen, or trifluoromethoxy; substituent R 2It is a C1-C10 alkyl, 3-6 carbocyclic alkyl, naphthyl, furanyl, phenyl, or a phenyl with one substituent, wherein the substituent is halogen, alkyl, alkazyl, alkoxy, or cyano; substituent R 3 It can be phenyl, carbonyl, halogen, or neopentanoyl.

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

[0027] Compound (I) is prepared by the following route:

[0028]

[0029] Example 1

[0030] The reaction equation is shown below:

[0031]

[0032] N-methyl-N,2-diphenylacetylene-1-sulfonamide (0.2 mmol), diphenyldiselenoether (0.1 mmol), and nitromethane (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, 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 purified by removing the solvent through a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: petroleum ether / ethyl acetate = 6 / 1) to obtain the target compound in 78% yield. 1 H NMR (400MHz, CDCl3): δ7.40 (d, J = 9.2Hz, 5H), 7.22 (d, J = 17.2Hz, 5H), 7.19 (d, J = 5.0Hz, 2H), 7.01–6.94 (m, 2H), 3.60 (s, 3H). 13 C NMR (100MHz, CDCl3): δ153.0,140.2,138.0,132.5,131.7,131.0,130.6,129.0,129.6,128.6,128.5,127.6,124.0,122.9,120.5,116.4,32.5.

[0033] Example 2

[0034] The reaction equation is shown below:

[0035]

[0036] N-methyl-N,2-diphenylacetylene-1-sulfonamide (0.2 mmol), diphenyldiselenoether (0.1 mmol), and acetonitrile (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, 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 purified by removing the solvent through a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: petroleum ether / ethyl acetate = 6 / 1) to obtain the target compound in 71% yield.

[0037] Example 3

[0038] The reaction equation is shown below:

[0039]

[0040] N-methyl-N,2-diphenylacetylene-1-sulfonamide (0.2 mmol), diphenyldiselenoether (0.1 mmol), and carbon tetrachloride (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, 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 purified by removing the solvent through a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: petroleum ether / ethyl acetate = 6 / 1) to obtain the target compound in a yield of 67%.

[0041] Example 4

[0042] The reaction equation is shown below:

[0043]

[0044] 2-(4-(tert-butyl)phenyl)-N-methyl-N-phenylethyn-1-sulfonamide (0.2 mmol), diphenyldiselenoether (0.1 mmol), and nitromethane (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, 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 purified by removing the solvent through a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: petroleum ether / ethyl acetate = 5 / 1) to obtain the target compound in 78% yield. 1 H NMR (400MHz, CDCl3): 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). 13C NMR (100MHz, CDCl3): δ152.9,152.0,141.1,134.3,132.2,131.7,131.3,130. 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 below:

[0047] 2-(4-(cyano)phenyl)-N-methyl-N-phenylethyn-1-sulfonamide (0.2 mmol), diphenyldiselenoether (0.1 mmol), and nitromethane (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, 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 purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: petroleum ether / ethyl acetate = 6 / 1) to obtain the target compound in 70% yield. 1 H NMR (400MHz, CDCl3): δ7.75–7.62(m,2H),7.55(m,1H),7.39–7.41(m,2H),7.23(s,1 H),7.30–7.21(m,5H),7.10–7.06(m,1H),6.91(dd,J=8.1,1.4Hz,1H),3.58(s,3H). 13 C NMR (100MHz, CDCl3): δ151.5,141.8,141.1,132.3,132.4,132.3,130.5,130.4,129.7,127.8,125.6,123.5,122.7,118.0,117.4,112.8,32.5.

[0048] Example 6

[0049] The reaction equation is shown below:

[0050]

[0051] N-methyl-2-(1-naphthyl)-N-phenylethyn-1-sulfonamide (0.2 mmol), diphenyldiselenoether (0.1 mmol), and nitromethane (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, 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 purified by removing the solvent through a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: petroleum ether / ethyl acetate = 4 / 1) to obtain the target compound in 85% yield. 1 H NMR (400MHz, CDCl3): 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, CDCl3): δ139.0,138.3,135.1,133.5,129.7,130.2,128.8,12 9.3,128.3,128.7,128.0,127.7,128.2,126.5,126.3,125.2,124.7,40.6.

[0052] Example 7

[0053] The reaction equation is shown below:

[0054]

[0055] N-methyl-N-phenyl-2-(2-thiophene) (0.2 mmol), diphenyldiselenoether (0.1 mmol), and nitromethane (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, 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 purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: petroleum ether / ethyl acetate = 5 / 1) to obtain the target compound in 82% yield. 1 H NMR (400MHz, CDCl3): δ7.52–7.40(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=3.5Hz,1H),3.51(s,3H).13 C NMR (100MHz, CDCl3): δ148.2,140.4,137.1,131.8,130.4,129.3,129.6,129.1,122.3,122.0,120.5,116.9,30.4.

[0056] Example 8

[0057] The reaction equation is shown below:

[0058]

[0059] N-(3,5-dimethylphenyl)-N-methyl-2-phenylethyn-1-sulfonamide (0.2 mmol), diphenyldiselenoether (0.1 mmol), and nitromethane (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, 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 purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: petroleum ether / ethyl acetate = 5 / 1) to obtain the target compound in 85% yield. 1 H NMR (400MHz, CDCl3): δ7.50–7.46(m,2H),7.42–7.33(m,3H),7.20–7.16(m,3H),7.19(d d,J=8.0,1.4Hz,2H),7.01(s,1H),6.81(s,1H),3.42(s,3H),2.34(s,3H),1.58(s,3H). 13 C NMR (100MHz, CDCl3): δ153.8,141.2,140.8,139.9,131.0,130.7,130.3,1 29.5,128.7,128.3,128.4,127.7,124.3,123.5,116.4,33.5,22.9,22.0.

[0060] Example 9

[0061] The reaction equation is shown below:

[0062]

[0063] N-methyl-2-phenyl-N-(4-neovalerylphenyl) (0.2 mmol), diphenyldiselenoether (0.1 mmol), and nitromethane (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, 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 purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: petroleum ether / ethyl acetate = 4 / 1) to obtain the target compound in 81% yield. 1 H NMR (400MHz, CDCl3): 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, CDCl3): 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 below:

[0066]

[0067] N-([1,1'-biphenyl]-4-yl)-N-methyl-2-phenylethyn-1-sulfonamide (0.2 mmol), diphenyldiselenoether (0.1 mmol), and nitromethane (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, 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 purified by removing the solvent through a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: petroleum ether / ethyl acetate = 7 / 1) to obtain the target compound in 86% yield. 1H NMR (400MHz, CDCl3): 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, CDCl3): δ153.5,140.3,140.0,137.9,136.3,133.1,130.3,130.7,1 29.7,128.8,129.5,129.3,128.6,128.4,127.4,126.7,125.1,124.8,116.8,32.6.

[0068] Example 11

[0069] The reaction equation is shown below:

[0070]

[0071] N,N,2-triphenylacetylene-1-sulfonamide (0.2 mmol), diphenyldiselenoether (0.1 mmol), and nitromethane (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, 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 purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: petroleum ether / ethyl acetate = 3 / 1) to obtain the target compound in 78% yield. 1 H NMR (400MHz, CDCl3): 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, CDCl3): δ133.2,131.3,130.6,130.2,129.1,129.6,128.8,128.4,127.9,127.6,123.3,121.1.

[0072] Example 12

[0073] The reaction equation is shown below:

[0074]

[0075] N-methyl-N,2-diphenylacetylene-1-sulfonamide (0.2 mmol), dimethyl diselenyl ether (0.1 mmol), and nitromethane (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, 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 purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: petroleum ether / ethyl acetate = 6 / 1) to obtain the target compound in 85% yield. 1 H NMR (400MHz, CDCl3): δ7.48–7.46(m,4H),7.32–7.23(m,3H),7.10–7.01(m,1H),6.94(dd,J=8.0,1.5Hz,1H),3.57(s,3H),2.38(s,3H). 13 C NMR (100MHz, CDCl3): δ150.5,139.8,138.5,131.3,130.5,128.7,128.9,128.3,124.6,123.6,122.4,116.9,31.6,11.1.

[0076] Example 13

[0077] The reaction equation is shown below:

[0078]

[0079] N-methyl-N,2-diphenylacetylene-1-sulfonamide (0.2 mmol), 1,2-bis(4-nitrophenyl)diselenoether (0.1 mmol), and nitromethane (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, 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 purified by removing the solvent using a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: petroleum ether / ethyl acetate = 5 / 1) to obtain the target compound in 79% yield. 1 H NMR (400MHz, CDCl3): δ8.12(d,J=8.5Hz,2H),7.63–7.48(m,3H),7.51–7.34(m,3H),7.32(d,J =8.2Hz, 1H), 7.19 (d, J = 7.0Hz, 2H), 7.12 (t, J = 7.6Hz, 1H), 7.00 (d, J = 6.6Hz, 1H), 3.65 (s, 3H). 13C NMR (100MHz, CDCl3): δ151.0,139.5,138.8,130.9,130.2,129.2,129.3,128.6,124.2,123.9,122.8,117.4,31.9,10.8

[0080] Example 14

[0081] The reaction equation is shown below:

[0082]

[0083] N-methyl-N,2-diphenylacetylene-1-sulfonamide (0.2 mmol), 1,2-bis(4-chlorophenyl)diselenoether (0.1 mmol), and nitromethane (2 mL) were added to a 20 mL test tube equipped with a magnetic stirrer. After the addition was complete, 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 purified by removing the solvent through a rotary evaporator. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: petroleum ether / ethyl acetate = 4 / 1) to obtain the target compound in 81% yield. 1 H NMR (400MHz, CDCl3): δ7.51–7.39(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 (100MHz, CDCl3): δ153.7,141.1,137.3,133.8,134.5,131.4,131.3,128.9,129.6,129.2,128.1,128.0,123.7,124.2,122.6,116.2,32.6.

[0084] Example 15: In vitro antitumor activity study

[0085] The in vitro proliferation inhibitory activity of the target compound 1a-1l against three human tumor cell lines (HGC-27, HepG2, and HCT-116) and normal human hepatocytes (LO2) was detected using the MTT assay. Detailed test results are shown in the table below:

[0086]

[0087] ND: Not detected

[0088] Test results showed that most of the compounds of this invention exhibited significant anti-cell proliferation activity, which was superior to the control drug fluorouracil (5-FU). In particular, compounds 1g, 1i, and 1l showed IC50 activity against three types of tumor cells. 50 The values ​​are all in single digits.

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

Claims

1. A method for preparing a visible light-promoted selenyl sulfonamide, characterized in that: The preparation method is as follows: In an organic solvent, (N-aryl)-alkynylsulfonamide of formula (I) and diselenyl ether of formula (II) are reacted under visible light irradiation with open stirring in the absence of metal catalyst and photocatalyst to obtain selenium-based sulfonamide compound of formula (III). The reaction equation is as follows: ， Among them, R 1 The radicals are furanyl, thiophenyl, pyridyl, naphthyl, phenyl, or phenyl substituted with one or more substituents, wherein the substituents are alkoxy, alkyl, halogen, or trifluoromethoxy; R 2 For C1-C 10 Alkyl, 3-6 carbocyclic alkyl, naphthyl, furanyl, phenyl, phenyl substituted with one substituent, wherein the substituent is halogen, alkyl, alkoxy, or cyano; R 3 It is phenyl, halogenated, or neopentanoyl; R 4 It is aryl or alkyl.

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

1.

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

5.

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

5. The method for preparing visible light-promoted selenium-based sulfonamides according to claim 1, characterized in that: The light source for the visible light reaction was a blue LED lamp; the open-top stirred reaction was carried out at room temperature for 20-30 hours.

6. The method for preparing visible light-promoted selenium-based sulfonamide according to claim 1, characterized in that: After stirring and reaction, the mixture was concentrated under reduced pressure and separated by column chromatography. A mixture of petroleum ether and ethyl acetate was used as the eluent, wherein the volume ratio of petroleum ether to ethyl acetate was 1–20:1.

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