Preparation method of bistrifluoromethyl selenide compound under visible light driving and medical use thereof

Abstract

The present application belongs to the technical field of organic synthesis chemistry, and particularly relates to a preparation method of a bis-trifluoromethyl selenide compound under visible light driving and medical use thereof. The preparation method of the bis-trifluoromethyl selenide compound comprises the following steps: taking olefin, trifluoromethyl selenide tetramethyl ammonium and bis-trifluoromethyl selenide diselenide as reaction raw materials, stirring and reacting under the condition of existing monovalent copper salt, visible light irradiation, and suitable temperature, so as to obtain the bis-trifluoromethyl selenide compound. The method has the advantages of mild reaction condition, simple operation, good functional group compatibility and the like. In addition, the bis-trifluoromethyl selenide compound provided by the present application shows good potential in anticonvulsant, and has the prospect of being further developed into an anticonvulsant drug.

Description

Technical Field

[0001] This invention belongs to the field of organic synthetic chemistry technology, specifically relating to a method for preparing bis(trifluoromethylselenoether) compounds under visible light-driven conditions and their pharmaceutical applications. Background Technology

[0002] Because the introduction of fluorine-containing groups can significantly alter the physical, chemical, and biological properties of parent molecules, organofluorine compounds have found widespread application in drug development and agrochemicals. Among the many organofluorine functional groups, trifluoromethylselenoyl (SeCF3) exhibits excellent lipophilicity due to its high hydrophobicity parameter (π=1.44), making it uniquely valuable in improving the bioavailability of compounds. Therefore, developing efficient and practical methods for introducing SeCF3 groups has become an important direction in synthetic chemistry research.

[0003] Although various synthetic methods for introducing single SeCF3 groups have been reported, systematic studies on the construction of bis(trifluoromethylselen) compounds are scarce. Therefore, developing synthetic strategies for structurally diverse and easily operable bis(trifluoromethylselen) compounds is not only of significant academic importance but also demonstrates strong application demand in drug molecule design and agrochemical development. Summary of the Invention

[0004] This invention provides a method for preparing a bis(trifluoromethylselenoether) compound under visible light and its pharmaceutical applications. One objective of this invention is to provide a class of bis(trifluoromethylselenoether) compounds with anticonvulsant activity. Another objective is to provide a method for preparing and purifying the above-mentioned bis(trifluoromethylselenoether) compound. A third objective is to apply the above-mentioned bis(trifluoromethylselenoether) compound to the preparation of clinical anticonvulsant drugs.

[0005] The above-mentioned objective of this invention is achieved through the following technical solution: In an organic solvent, using an olefin of formula (I), trifluoromethylselenomethyltetramethylammonium of formula (II), and bis(trifluoromethylselenomethyl)diselenoether of formula (III) as reactants, the reaction is carried out under stirring at a suitable temperature and under visible light irradiation in the presence of a monovalent copper salt. After the reaction is complete, volatiles are removed under vacuum, and the residue is purified by column chromatography to obtain the bis(trifluoromethylselenoether) compound of formula (IV); the reaction equation is shown below:

[0006]

[0007] The compound of formula (I) is an olefin, and Ar is phenyl, naphthyl, anthracene, furanyl, thiophene, or aryl substituted with one or more substituents, wherein the substituents are alkoxy, alkyl, halogen, cyano, or nitro.

[0008] Compound (II) is trifluoromethylselenomethylammonium; compound (III) is di(trifluoromethylseleno)diselenoether.

[0009] The molar ratio of the olefin of formula (I) to the trifluoromethylselenomethyltetramethylammonium of formula (II) and the di(trifluoromethylseleno)diselenoether of formula (III) is 1:(2-5):2, preferably 1:3:2.

[0010] The monovalent copper salt is selected from CuCl, CuBr, CuI, Cu(MeCN)4PF6, and Cu2SO4, with CuI being the preferred monovalent copper salt.

[0011] The organic solvent is selected from acetonitrile, toluene, N,N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, ethyl acetate, or 1,2-dichloroethane, with acetonitrile being the preferred organic solvent.

[0012] The light source for the visible light reaction is one of white fluorescent lamp, blue LED, or purple LED; the light source for the visible light reaction is blue LED; the reaction is carried out at room temperature under nitrogen protection with stirring, and the reaction time is 10 hours.

[0013] 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 (1-100):1.

[0014] The use of the bis(trifluoromethylselenoether) compounds of the present invention, and their pharmaceutically acceptable salts, solvates, or hydrates, in the preparation of anticonvulsant drugs. The derivatives exhibit significant efficacy in treating convulsions.

[0015] On the other hand, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of an active ingredient and one or more pharmaceutically acceptable carriers or diluents; said active ingredient is selected from any one or more of the aforementioned bis(trifluoromethylselenoether) compounds, their pharmaceutically acceptable salts, solvates or hydrates.

[0016] The beneficial effects of this invention are as follows:

[0017] (1) The present invention uses visible light (such as blue LED) as an energy source to drive the reaction, avoiding the harsh conditions such as high temperature, high pressure or strong oxidants that may be used in traditional methods.

[0018] (2) This invention can efficiently introduce two trifluoromethylselenide groups at the ortho position of an olefin in a single reaction, directly generating a bis(trifluoromethylselenide) ether compound. This method is simple to operate, requires no multi-step synthesis, and significantly improves the synthesis efficiency.

[0019] (3) Some of the bis(trifluoromethylselenoether) derivatives prepared by this method have good anticonvulsant effects and are expected to be used to prepare new anticonvulsant drugs. Detailed Implementation

[0020] 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.

[0021] This invention provides the following technical solution: In an organic solvent, using an olefin of formula (I), trifluoromethylselenomethyltetramethylammonium of formula (II), and di(trifluoromethylselenomethyl)diselenoether of formula (III) as raw materials, and in the presence of a monovalent copper salt, the mixture is stirred and reacted under suitable temperature and visible light irradiation conditions to obtain the bis(trifluoromethylselenoether) compound of formula (IV). The reaction equation is shown below:

[0022]

[0023] Compound (I) is an olefin, where Ar is phenyl, naphthyl, anthracene, furanyl, thiophene, or an aryl group substituted with one or more substituents, wherein the substituents are alkoxy, alkyl, halogen, cyano, or nitro; compound (II) is trifluoromethylselenomethyltetramethylammonium; and compound (III) is di(trifluoromethylselenomethyl)diselenoether.

[0024] Example 1

[0025] The reaction equation is shown below:

[0026]

[0027] Under a nitrogen atmosphere, trifluoromethylselenomethylammonium (1.5 mmol) and CuI (0.5 mmol) were added sequentially to a 20 mL Schlenk tube equipped with a magnetic stirrer. The reaction system was evacuated and purged three times with nitrogen. Then, under an inert atmosphere, 4-tert-butylstyrene (0.5 mmol), diseleno(trifluoroselenomethyl)diselenoether (1 mmol), and anhydrous acetonitrile (2 mL) were added via syringe. After the addition was complete, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed, the volatiles were removed under vacuum, and the residue was purified by silica gel column chromatography to obtain the target compound 1a in 80% yield. 1H NMR(400 MHz, CDCl3) δ 7.41 (d, J = 8.2 Hz, 2H), 7.22 (d, J = 8.2 Hz, 2H), 4.56(dd, J = 10.5,5.2 Hz, 1H), 3.60 (dd, J = 14.1, 5.3 Hz, 1H), 3.40 (dd, J =13.4, 10.9 Hz, 1H), 1.37 (s, 9H). 13 C NMR (100 MHz, CDCl3) δ 151.9,131.2,130.1, 133.3, 127.1,126.7, 48.2, 35.5, 34.7, 31.9.

[0028] Example 2

[0029] Under a nitrogen atmosphere, trifluoromethylselenomethylammonium (1.5 mmol) and CuI (0.5 mmol) were added sequentially to a 20 mL Schlenk tube equipped with a magnetic stirrer. The reaction system was evacuated and purged three times with nitrogen. Then, under an inert atmosphere, 4-tert-butylstyrene (0.5 mmol), diseleno(trifluoromethylselenomethyl)diselenoether (1 mmol), and anhydrous toluene (2 mL) were added via syringe. After the addition was complete, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed, the volatiles were removed under vacuum, and the residue was purified by silica gel column chromatography to obtain the target compound 1a in 71% yield.

[0030] Example 3

[0031] Under a nitrogen atmosphere, trifluoromethylselenomethylammonium (1.5 mmol) and CuI (0.5 mmol) were added sequentially to a 20 mL Schlenk tube equipped with a magnetic stirrer. The reaction system was evacuated and purged three times with nitrogen. Then, under an inert atmosphere, 4-tert-butylstyrene (0.5 mmol), diseleno(trifluoromethylselenomethyl)diselenoether (1 mmol), and anhydrous ethyl acetate (2 mL) were added via syringe. After the addition was complete, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed, the volatiles were removed under vacuum, and the residue was purified by silica gel column chromatography to obtain the target compound 1a in 62% yield.

[0032] Example 4

[0033] Under a nitrogen atmosphere, trifluoromethylselenomethylammonium (1 mmol) and CuI (0.5 mmol) were added sequentially to a 20 mL Schlenk tube equipped with a magnetic stirrer. The reaction system was evacuated and purged three times with nitrogen. Then, under an inert atmosphere, 4-tert-butylstyrene (0.5 mmol), diseleno(trifluoromethylselenomethyl)diselenoether (1 mmol), and anhydrous acetonitrile (2 mL) were added via syringe. After the addition was complete, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed, the volatiles were removed under vacuum, and the residue was purified by silica gel column chromatography to obtain the target compound 1a in 73% yield.

[0034] Example 5

[0035] Under a nitrogen atmosphere, trifluoromethylselenomethylammonium (1.5 mmol) and CuCl (0.5 mmol) were added sequentially to a 20 mL Schlenk tube equipped with a magnetic stirrer. The reaction system was evacuated and purged three times with nitrogen. Then, under an inert atmosphere, 4-tert-butylstyrene (0.5 mmol), diseleno(trifluoroselenomethyl)diselenoether (1 mmol), and anhydrous acetonitrile (2 mL) were added via syringe. After the addition was complete, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed, the volatiles were removed under vacuum, and the residue was purified by silica gel column chromatography to obtain the target compound 1a in 72% yield.

[0036] Example 6

[0037] Under a nitrogen atmosphere, trifluoromethylselenomethylammonium (1.5 mmol) and Cu₂SO₄ (0.5 mmol) were added sequentially to a 20 mL Schlenk tube equipped with a magnetic stirrer. The reaction system was evacuated and purged with nitrogen three times. Then, under an inert atmosphere, 4-tert-butylstyrene (0.5 mmol), diseleno(trifluoroselenomethyl)diselenoether (1 mmol), and anhydrous acetonitrile (2 mL) were added via syringe. After the addition was complete, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed, the volatiles were removed under vacuum, and the residue was purified by silica gel column chromatography to obtain the target compound 1a in 68% yield.

[0038] Example 7

[0039] The reaction equation is shown below:

[0040]

[0041] Under a nitrogen atmosphere, trifluoromethylselenomethylammonium (1.5 mmol) and CuI (0.5 mmol) were added sequentially to a 20 mL Schlenk tube equipped with a magnetic stirrer. The reaction system was evacuated and purged with nitrogen three times. Then, under an inert atmosphere, 4-methoxystyrene (0.5 mmol), diseleno(trifluoromethylselenomethyl)diselenoether (1 mmol), and anhydrous acetonitrile (2 mL) were added via syringe. After the addition was complete, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed, the volatiles were removed under vacuum, and the residue was purified by silica gel column chromatography to obtain the target compound 1b in 65% yield. 1 H NMR (400 MHz, CDCl3) δ 7.23 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.5 Hz, 2H), 4.56 (dd, J =10.4, 5.3 Hz, 1H), 3.80 (d, J = 7.4 Hz, 3H), 3.65 (dd, J = 14.1, 5.2Hz, 1H), 3.40 (dd, J = 13.4, 11.0 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 161.2,131.8, 130.0, 129.0,128.5, 114.5, 55.5, 48.1, 36.5.

[0042] Example 8

[0043] The reaction equation is shown below:

[0044]

[0045] Under a nitrogen atmosphere, trifluoromethylselenomethylammonium (1.5 mmol) and CuI (0.5 mmol) were added sequentially to a 20 mL Schlenk tube equipped with a magnetic stirrer. The reaction system was evacuated and purged with nitrogen three times. Then, under an inert atmosphere, 4-bromostyrene (0.5 mmol), diseleno(trifluoromethylselenomethyl)diselenoether (1 mmol), and anhydrous acetonitrile (2 mL) were added via syringe. After the addition was complete, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed, the volatiles were removed under vacuum, and the residue was purified by silica gel column chromatography to obtain the target compound 1c in 72% yield. 1H NMR (400MHz, CDCl3) δ 7.54 (d, J = 8.3 Hz, 2H), 7.19 (d, J = 8.2 Hz, 2H), 4.50 (dd, J= 10.3, 5.4 Hz, 1H), 3.54 (dd, J = 14.2, 5.5 Hz, 1H), 3.34 (dd, J = 14.9,10.4 Hz, 1H). 13 C NMR (100MHz, CDCl3) δ 135.1, 132.51, 130.1, 130.5, 128.5, 125.3, 47.1, 35.7.

[0046] Example 9

[0047] The reaction equation is shown below:

[0048]

[0049] Under a nitrogen atmosphere, trifluoromethylselenomethylammonium (1.5 mmol) and CuI (0.5 mmol) were added sequentially to a 20 mL Schlenk tube equipped with a magnetic stirrer. The reaction system was evacuated and purged with nitrogen three times. Then, under an inert atmosphere, 4-chlorostyrene (0.5 mmol), diseleno(trifluoromethylselenomethyl)diselenoether (1 mmol), and anhydrous acetonitrile (2 mL) were added via syringe. After the addition was complete, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed, the volatiles were removed under vacuum, and the residue was purified by silica gel column chromatography to obtain the target compound 1d, with a yield of 70%. 1 H NMR (400MHz, CDCl3) δ 7.37 (d, J = 8.3 Hz, 2H), 7.25 (d, J = 8.6 Hz, 2H), 4.50 (dd, J= 10.4,5.4 Hz, 1H), 3.61 (dd, J = 14.4, 5.6 Hz, 1H), 3.34 (dd, J = 14.2, 10.4Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 135.0, 134.1, 131.4, 128.9, 129.5, 128.0, 48.1, 35.6.

[0050] Example 10

[0051] The reaction equation is shown below:

[0052]

[0053] Under a nitrogen atmosphere, trifluoromethylselenomethylammonium (1.5 mmol) and CuI (0.5 mmol) were added sequentially to a 20 mL Schlenk tube equipped with a magnetic stirrer. The reaction system was evacuated and purged with nitrogen three times. Then, under an inert atmosphere, 4-nitrostyrene (0.5 mmol), diseleno(trifluoromethylselenomethyl)diselenoether (1 mmol), and anhydrous acetonitrile (2 mL) were added via syringe. After the addition was complete, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed, the volatiles were removed under vacuum, and the residue was purified by silica gel column chromatography to obtain the target compound 1e in 71% yield. 1 H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 8.5 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 4.65 (dd, J = 10.5, 5.7 Hz, 1H), 3.60 (dd, J = 14.7, 5.9 Hz, 1H), 3.30 (dd, J =14.1, 10.5 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 147.4, 145.6, 128.0, 131.4, 129.5, 123.6, 48.5, 35.0.

[0054] Example 11

[0055] The reaction equation is shown below:

[0056]

[0057] Under a nitrogen atmosphere, trifluoromethylselenomethylammonium (1.5 mmol) and CuI (0.5 mmol) were added sequentially to a 20 mL Schlenk tube equipped with a magnetic stirrer. The reaction system was evacuated and purged with nitrogen three times. Then, under an inert atmosphere, 4-vinylphenylacetate (0.5 mmol), diseleno(trifluoromethylselenomethyl)diselenoether (1 mmol), and anhydrous acetonitrile (2 mL) were added via syringe. After the addition was complete, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed, the volatiles were removed under vacuum, and the residue was purified by silica gel column chromatography to obtain the target compound 1f in 62% yield. 1H NMR (400 MHz, CDCl3) δ 7.30 (d, J = 8.6 Hz, 2H), 7.10 (d, J = 8.7 Hz, 2H), 4.54 (dd, J= 11.2, 5.4 Hz, 1H), 3.55 (dd, J = 14.2, 5.6 Hz, 1H), 3.30 (dd, J= 14.5, 10.7 Hz, 1H), 2.31 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.2, 150.0, 135.1, 131.5, 130.9, 128.7, 122.1, 48.0, 35.6, 21.5.

[0058] Example 12

[0059] The reaction equation is shown below:

[0060]

[0061] Under a nitrogen atmosphere, trifluoromethylselenomethylammonium (1.5 mmol) and CuI (0.5 mmol) were added sequentially to a 20 mL Schlenk tube equipped with a magnetic stirrer. The reaction system was evacuated and purged with nitrogen three times. Then, under an inert atmosphere, 4-vinylbenzoic acid (0.5 mmol), diseleno(trifluoromethylseleno)diselenoether (1 mmol), and anhydrous acetonitrile (2 mL) were added via syringe. After the addition was complete, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed, the volatiles were removed under vacuum, and the residue was purified by silica gel column chromatography to obtain 1 g of the target compound, with a yield of 72%. 1 H NMR (400 MHz, CDCl3) δ 10.70 (s, 1H), 8.18 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.0Hz, 2H), 4.60 (dd, J = 10.1, 5.7 Hz, 1H), 3.60 (dd, J = 14.7, 5.6 Hz, 1H),3.40 (dd, J = 14.1,10.7 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ174.7, 140.5, 131.5,130.5,130.1, 129.8, 128.0, 48.3, 35.5.

[0062] Example 13

[0063] The reaction equation is shown below:

[0064]

[0065] Under a nitrogen atmosphere, trifluoromethylselenomethylammonium (1.5 mmol) and CuI (0.5 mmol) were added sequentially to a 20 mL Schlenk tube equipped with a magnetic stirrer. The reaction system was evacuated and purged with nitrogen three times. Then, under an inert atmosphere, 2-vinylnaphthalene (0.5 mmol), diseleno(trifluoromethylselenomethyl)diselenoether (1 mmol), and anhydrous acetonitrile (2 mL) were added via syringe. After the addition was complete, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed, the volatiles were removed under vacuum, and the residue was purified by silica gel column chromatography to obtain the target compound in 1 h, with a yield of 69%. 1 H NMR (400MHz, CDCl3) δ 8.00 - 7.89 (m, 3H), 7.82 (s, 1H), 7.60 - 7.50 (m, 2H), 7.46(dd, J = 8.4,1.6 Hz, 1H), 4.80 (dd, J = 10.4, 5.3 Hz, 1H), 3.75 (dd, J =14.1, 5.7 Hz, 1H), 3.60 (dd, J = 14.7, 10.2 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ134.1, 133.2, 133.7,130.4, 130.1, 129.7, 128.7, 128.6, 128.1, 127.8, 127.4125.8, 48.1,35.1.

[0066] Example 14

[0067] The reaction equation is shown below:

[0068]

[0069] Under a nitrogen atmosphere, trifluoromethylselenomethylammonium (1.5 mmol) and CuI (0.5 mmol) were added sequentially to a 20 mL Schlenk tube equipped with a magnetic stirrer. The reaction system was evacuated and purged with nitrogen three times. Then, under an inert atmosphere, 9-vinylanthracene (0.5 mmol), diseleno(trifluoromethylselenomethyl)diselenoether (1 mmol), and anhydrous acetonitrile (2 mL) were added via syringe. After the addition was complete, a blue LED lamp was placed 2 cm away from the test tube, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed, the volatiles were removed under vacuum, and the residue was purified by silica gel column chromatography to obtain the target compound 1i in 62% yield. 1 H NMR (400MHz, CDCl3) δ 8.51 (s, 1H), 8.24 (d, J = 9.0 Hz, 1H), 8.20 - 8.04 (m, 3H), 7.65 (dd,J = 8.4, 7.5 Hz, 1H), 7.60 - 7.54 (m, 1H), 7.50 (dd, J = 151, 8.4Hz, 2H), 6.26 -5.91 (m, 1H), 4.14 (dd, J= 14.0, 10.4 Hz, 1H), 4.07 (ddd, J =14.7, 5.4, 1.8 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 132.9,131.4, 130.7, 130.6,130.0, 129.8, 129.1, 129.0, 128.7, 128.5, 127.7, 126.8, 125.1, 125.0, 123.9,122.7, 42.4,36.7.

[0070] Example 15

[0071] Investigation of the anticonvulsant activity of the compound.

[0072] The study employed a maximal electroconvulsive shock (MES) model for validation. Twenty-four hours prior to the experiment, mice were screened by 0.2 seconds of ear electrode stimulation with 110V, 50Hz alternating current; those exhibiting hind limb rigidity were eligible for the experiment. During the experiment, each compound was injected intraperitoneally, followed by electrical stimulation with 110V, 50Hz alternating current 30 minutes later. The protective index (PI) of the anticonvulsant drugs of the studied compounds was determined by the median toxic dose (TD) measured in the maximal electroconvulsive shock model experiment. 50 The value divided by the corresponding half-maximal effective dose (ED) 50The values ​​were calculated. The data were also compared with valproic acid, an anticonvulsant drug with clear clinical application value. All substances were suspended in Tween 80 (1% aqueous solution) and administered intraperitoneally as a single dose of 10 mL / kg. Fresh solutions were prepared each day of the experiment. Specific experimental results are shown below:

[0073]

[0074] Based on the maximum electroshock screening data, compounds 1d, 1e, and 1f exhibited high activity (ED) in terms of pharmacological efficacy. 50 <200 mg / kg), exceeding valproic acid, with compound 1e exhibiting the strongest activity; the remaining compounds showed moderate or low activity. Regarding safety, compound 1b has a TD... 50 The highest PI (prostaglandin B) and lowest toxicity were observed in compounds 1a, 1b, and 1i, while 1c, 1g, and 1i showed relatively high toxicity. A comprehensive evaluation of the potential drug properties (PIs) revealed that compounds 1a, 1b, and 1e all had higher PIs than valproic acid. Compound 1b had the highest PI value (3.0), exhibiting moderate activity but outstanding safety and the widest therapeutic window, making it the compound with the best overall drug development potential in this series. Compound 1e, on the other hand, combined high activity with a good PI (2.4), making it another potential candidate compound. In summary, compounds 1b and 1e in this series have the greatest potential for further optimization.

[0075] 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 bis(trifluoromethylselenoether) compound, characterized in that, The structural formula of the bis(trifluoromethylselenoether) compound is as follows: , Ar can be 4-tert-butylphenyl, 4-methoxyphenyl, 4-bromophenyl, 4-chlorophenyl, 4-nitrophenyl, 4-acetylphenyl, 4-carboxyphenyl, or 2-naphthyl.

2. A method for preparing a bis(trifluoromethylselenoether) compound under visible light-driven conditions, characterized in that, The preparation method is as follows: In an organic solvent, using the olefin shown in formula (I), trifluoromethylselenomethyltetramethylammonium shown in formula (II), and di(trifluoromethylselenomethyl)diselenoether shown in formula (III) as raw materials, the reaction is carried out under stirring in the presence of a monovalent copper salt and under visible light irradiation to obtain the bis(trifluoromethylselenoether) compound shown in formula (IV). The reaction equation is as follows: ， Ar can be 4-tert-butylphenyl, 4-methoxyphenyl, 4-bromophenyl, 4-chlorophenyl, 4-nitrophenyl, 4-acetylphenyl, 4-carboxyphenyl, or 2-naphthyl.

3. The method for preparing the bis(trifluoromethylselenide) ether compound under visible light driven according to claim 2, characterized in that, The molar ratio of the olefin with the structure shown in formula (I), the trifluoromethylselenomethyltetramethylammonium with the structure shown in formula (II), and the di(trifluoromethylselenomethyl)diselenoether with the structure shown in formula (III) is 1:2 to 5:

2.

4. The method for preparing the bis(trifluoromethylselenide) ether compound under visible light driven according to claim 2, characterized in that, The molar ratio of the olefin with the structure shown in formula (I), the trifluoromethylselenomethyltetramethylammonium with the structure shown in formula (II), and the di(trifluoromethylselenomethyl)diselenoether with the structure shown in formula (III) is 1:3:

2.

5. The method for preparing the bis(trifluoromethylselenide) compound under visible light driven according to claim 2, characterized in that, The monovalent copper salt is selected from CuCl, CuBr, CuI, Cu(MeCN)4PF6, and Cu2SO4; the organic solvent is selected from acetonitrile, toluene, N,N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, ethyl acetate, or 1,2-dichloroethane.

6. The method for preparing the bis(trifluoromethylselenide) compound under visible light driven according to claim 2, characterized in that, The light source for the visible light reaction is one of a white fluorescent lamp, a blue LED, or a purple LED; the reaction is carried out at room temperature under nitrogen protection with stirring, and the reaction time is 10 hours.

7. The method for preparing the bis(trifluoromethylselenide) ether compound under visible light driven according to claim 2, 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 1–100:

1.

8. A pharmaceutical composition, characterized in that, The pharmaceutical composition comprises the bis(trifluoromethylselenoether) compound according to claim 1, a medically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

9. The use of a pharmaceutical composition according to claim 8, characterized in that, The pharmaceutical composition is used to prepare a drug for treating convulsion-related diseases.

10. The use of the pharmaceutical composition according to claim 9, characterized in that, Seizure-related diseases include all types of seizures.

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