A quinoxaline-2(1h)-selenone derivative, a preparation method and medical use thereof
The synthesis of quinoxaline-2(1H)-selenoketone derivatives by heating the reaction of o-phenylenediamine, aryl ethyl ketone, and selenium powder solves the problem of toxic selenium reagents in traditional methods, realizes an efficient and safe synthesis method, and demonstrates its application potential in pharmaceutical and materials science.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- NANTONG UNIV
- Filing Date
- 2026-03-16
- Publication Date
- 2026-06-09
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthetic chemistry technology, specifically relating to a quinoxaline-2(1H)-selenoketone derivative, its preparation method, and its pharmaceutical uses. Background Technology
[0002] Quinoxalines are an important class of nitrogen-containing heterocyclic structural units, with their benzopyrazine bicyclic skeletons widely found in a variety of useful molecules, from bioactive molecules to functional materials. In medicinal chemistry, quinoxaline derivatives, as multifunctional pharmacophores, exhibit a wide range of pharmacological properties, including antibacterial, antiviral, anticancer, anti-inflammatory, analgesic, and therapeutic effects for diabetes and Alzheimer's disease. Some derivatives also exert antitumor effects by inhibiting kinases such as PI3K and EGFR. In materials science, quinoxaline derivatives also show great promise, being widely used in the development of organic light-emitting diodes, fluorescent sensors, organic photovoltaics, and electrochromic materials. Therefore, how to efficiently construct such skeletons from readily available raw materials has long been a focus of attention for organic chemists, medicinal chemists, and materials scientists.
[0003] Furthermore, selenium, an essential trace element for the human body, mainly exists in the active site of selenoproteins in the form of selenocysteine, playing a key role in antioxidation, regulation of thyroid hormones, and enhancement of immune function. Introducing selenium atoms into the quinoxaline backbone not only preserves the biological activity of the parent nucleus, but its larger atomic radius and lower electronegativity may also bring unique reactivity.
[0004] Among numerous selenium introduction strategies, elemental selenium is the preferred choice for developing ideal selenization reagents due to its unique reactivity, relatively low cost, and user-friendly operation. Using it to construct selenium-containing heterocyclic derivatives effectively avoids the use of traditional toxic, odorous, and highly reactive selenium reagents or their precursors. Based on this, this application develops a one-step method for constructing quinoxaline-2(1H)-selenoketone derivatives using trimethylcyanosilane (TMSCN) as a reaction promoter and elemental selenium as the selenium source, and further explores its potential applications. Summary of the Invention
[0005] This invention provides a method for preparing and applying quinoxaline-2(1H)-selenophenone derivatives directly synthesized from o-phenylenediamine, aryl ethyl ketone, and selenium powder. One objective of this invention is to provide a class of quinoxaline-2(1H)-selenophenone derivatives. Another objective is to provide a method for preparing and purifying the above-mentioned quinoxaline-2(1H)-selenophenone derivatives. A third objective is to apply the above-mentioned quinoxaline-2(1H)-selenophenone derivatives to the preparation of drugs for treating type II diabetes.
[0006] The above-mentioned objective of the present invention is achieved through the following technical solution:
[0007] A quinoxaline-2(1H)-selenophenone derivative, wherein the structural formula of the quinoxaline-2(1H)-selenophenone derivative is as follows: Wherein, substituent R is alkyl, alkoxy, halogen or phenyl, and Ar is phenyl, naphthyl, pyridyl, thiophene, or phenyl substituted with one or more substituents, wherein the substituent is alkyl, alkoxy, halogen, nitro, trifluoromethyl, ester or cyano.
[0008] A method for preparing a quinoxaline-2(1H)-selenophenone derivative, wherein the preparation method comprises:
[0009] In an organic solvent, using o-phenylenediamine as shown in formula (I), aryl ethyl ketone as shown in formula (II), and selenium powder as shown in formula (III) as raw materials, and TMSCN as a reaction promoter, a heating reaction is carried out under certain temperature conditions to obtain the quinoxaline-2(1H)-selenoketone derivative shown in formula (IV). The reaction equation is shown below:
[0010] .
[0011] Preferably, the structure of o-phenylenediamine is as follows: The structure of aryl ethyl ketone is ;
[0012] Wherein, substituent R is alkyl, alkoxy, halogen or phenyl, and Ar is phenyl, naphthyl, pyridyl, thiophene, or phenyl substituted with one or more substituents, wherein the substituent is alkyl, alkoxy, halogen, nitro, trifluoromethyl, ester or cyano.
[0013] Preferably, the molar ratio of o-phenylenediamine (I), aryl ethyl ketone (II), and selenium powder (III) is 1.2:1:1-1.2:1:2, and more preferably 1.2:1:1.5.
[0014] Preferably, the organic solvent is one or more of dimethyl sulfoxide, N,N-dimethylformamide, xylene, and N-methylpyrrolidone, with dimethyl sulfoxide being the most preferred.
[0015] Preferably, the reaction is 120. o The reaction is carried out under heating at C for 8-16 hours.
[0016] Preferably, after the reaction is completed, the reaction solution is cooled to room temperature, filtered to remove residual selenium powder, extracted with dichloromethane, the organic phase is separated, dried with anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography; a dichloromethane / methanol mixture is used as the eluent, wherein the volume ratio of dichloromethane to methanol is 100 to 30:1.
[0017] On the other hand, the present invention also provides a pharmaceutical composition comprising a quinoxaline-2(1H)-selenophenone derivative prepared by the above method, a medically acceptable salt, solvate or hydrate thereof, and a pharmaceutically acceptable carrier or excipient.
[0018] The use of the above-described pharmaceutical composition in the preparation of a medicament for the prevention and / or treatment of type II diabetes.
[0019] Preferably, the quinoxaline-2(1H)-selenophenone derivatives and their pharmaceutically acceptable salts, solvates, or hydrates all possess α-glucosidase inhibitory activity. The compounds exhibit significant inhibitory activity against α-glucosidase.
[0020] Compared with the prior art, the beneficial effects of the present invention are as follows:
[0021] (1) Innovative Synthesis Method: This invention provides a preparation method that does not require metal catalysts or chemical oxidants. It directly uses o-phenylenediamine, aryl ethyl ketone, and selenium powder as raw materials to synthesize quinoxaline-2(1H)-selenoketone derivatives through heating reaction. This method is simple to operate, has mild reaction conditions, and high yield.
[0022] (2) Avoid using toxic reagents: The present invention uses elemental selenium as the selenium source, which avoids the use of toxic, foul-smelling and highly active selenium reagents in traditional methods, thus improving operational safety and environmental friendliness.
[0023] (3) Significant biological activity: Pharmacological activity tests show that the quinoxaline-2(1H)-selenoketone derivative synthesized in this invention has significant inhibitory activity against α-glucosidase, showing potential application value in the prevention and treatment of type II diabetes.
[0024] (4) Expanding the application field of selenium heterocyclic compounds: This invention introduces selenium into the quinoxaline skeleton, which not only enriches the structural types of selenium-containing heterocyclic compounds, but also provides new ideas and foundations for the application of selenium in medicinal chemistry and materials science. Detailed Implementation
[0025] 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.
[0026] This invention provides the following technical solution: In an organic solvent, using o-phenylenediamine as shown in formula (I), aryl ethyl ketone as shown in formula (II), and selenium powder as shown in formula (III) as raw materials, and TMSCN as a reaction promoter, a heating reaction is carried out under certain temperature conditions to obtain the quinoxaline-2-selenoketone compound shown in formula (IV). The reaction equation is shown below:
[0027]
[0028] Wherein, substituent R is alkyl, alkoxy, halogen or phenyl, and Ar is phenyl, naphthyl, pyridyl, thiophene, or phenyl substituted with one or more substituents, wherein the substituent is alkyl, alkoxy, halogen, nitro, trifluoromethyl, ester or cyano.
[0029] Example 1
[0030] The reaction equation is shown below:
[0031]
[0032] An o-phenylenediamine (1.2 mmol), acetophenone (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 50 / 1) to give the target compound 1a in 75% yield.
[0033] Example 2
[0034] The reaction equation is shown below:
[0035]
[0036] An o-phenylenediamine (1.2 mmol), p-methylacetophenone (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 40 / 1) to give the target compound 1b in 74% yield.
[0037]
[0038] Example 3
[0039] The reaction equation is shown below:
[0040]
[0041] An o-phenylenediamine (1.2 mmol), p-chloroacetophenone (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 80 / 1) to give the target compound 1c in 90% yield.
[0042]
[0043] Example 4
[0044] The reaction equation is shown below:
[0045]
[0046] An o-phenylenediamine (1.2 mmol), p-methoxyacetophenone (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 50 / 1) to obtain the target compound 1d, with a yield of 81%.
[0047]
[0048] Example 5
[0049] The reaction equation is shown below:
[0050]
[0051] An o-phenylenediamine (1.2 mmol), p-trifluoromethylacetophenone (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 40 / 1) to give the target compound 1e in 63% yield.
[0052]
[0053] Example 6
[0054] The reaction equation is shown below:
[0055]
[0056] An o-phenylenediamine (1.2 mmol), p-nitroacetophenone (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 30 / 1) to give the target compound 1f in 61% yield.
[0057]
[0058] Example 7
[0059] The reaction equation is shown below:
[0060]
[0061] An o-phenylenediamine (1.2 mmol), p-phenylacetophenone (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 50 / 1) to give 1 g of the target compound, with a yield of 81%.
[0062]
[0063] Example 8
[0064] The reaction equation is shown below:
[0065]
[0066] An o-phenylenediamine (1.2 mmol), methyl p-acetylbenzoate (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 50 / 1) to obtain the target compound in 1 h, with a yield of 65%.
[0067]
[0068] Example 9
[0069] The reaction equation is shown below:
[0070]
[0071] An o-phenylenediamine (1.2 mmol), p-cyanoacetophenone (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 60 / 1) to give the target compound 1i in 64% yield.
[0072]
[0073] Example 10
[0074] The reaction equation is shown below:
[0075]
[0076] An o-phenylenediamine (1.2 mmol), 2-acetylnaphthalene (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 60 / 1) to obtain the target compound 1j in 70% yield.
[0077]
[0078] Example 11
[0079] The reaction equation is shown below:
[0080]
[0081] An o-phenylenediamine (1.2 mmol), 4-acetylpyridine (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 30 / 1) to give the target compound 1K in 82% yield.
[0082]
[0083] Example 12
[0084] The reaction equation is shown below:
[0085]
[0086] An o-phenylenediamine (1.2 mmol), 2-acetylthiophene (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 30 / 1) to give 1 L of the target compound, with a yield of 67%.
[0087]
[0088] Example 13
[0089] The reaction equation is shown below:
[0090]
[0091] 4,5-Dimethyl-1,2-phenylenediamine (1.2 mmol), acetophenone (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 30 / 1) to give the target compound 1 M in 65% yield.
[0092] Example 14
[0093] The reaction equation is shown below:
[0094]
[0095] 4,5-Dichloro-1,2-phenylenediamine (1.2 mmol), acetophenone (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 100 / 1) to obtain the target compound 1n in 73% yield.
[0096]
[0097] Example 15
[0098] The reaction equation is shown below:
[0099]
[0100] 4,5-Dimethoxy-1,2-phenylenediamine (1.2 mmol), acetophenone (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 30 / 1) to give the target compound 1o in 73% yield.
[0101]
[0102] Example 16
[0103] The reaction equation is shown below:
[0104]
[0105] 2,3-Diaminonaphthalene (1.2 mmol), acetophenone (1.0 mmol), selenium powder (1.5 mmol), trimethylcyanosilane (4 mmol), and dimethyl sulfoxide (0.2 mL) were added to a 20 mL pressure-resistant tube equipped with a magnetic stirrer. After addition, the reaction solution was reacted at 120 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, and extracted with dichloromethane to separate the organic phase. The organic phase was dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography (silica gel size 200-300 mesh, eluent: dichloromethane / methanol = 50 / 1) to give the target compound 1p in 78% yield.
[0106]
[0107] Example 17
[0108] The activity of the compound against α-glucosidase was investigated.
[0109] The activity of α-glucosidase was determined using the p-nitrophenyl-α-D-glucopyranoside (pNPG) method. This method uses pNPG as a substrate, which is hydrolyzed by α-glucosidase to produce p-nitrophenol (pNP) and glucose. pNP is yellow and exhibits characteristic strong UV absorption at 405 nm. Acarbose was used as a positive control. The inhibition rate of the sample against α-glucosidase was calculated by detecting the amount of product generated in the reaction system after the addition of the sample.
[0110] The specific operating steps are as follows: In a 96-well plate, add 80 μL of sample solution (compound 1a-1p, in PBS buffer at pH 7.2) and 20 μL of α-glucosidase solution (2 U / mL, prepared with PBS buffer at pH 7.2), mix well, and incubate at 37°C. o Incubate at 37°C for 15 min; then add 20 μL of 5 mmol / L pNPG solution to initiate the reaction. o After incubation at C for 15 min, the reaction was terminated by adding 80 μL of 1 mol / L Na₂CO₃ solution. The blank control group was prepared by replacing the sample solution with 80 μL of 1% PBS. The release amount of pNP was quantitatively analyzed by measuring the absorbance (A) at 405 nm.
[0111] The experiment included four groups: an enzyme activity group (20 μL enzyme + 80 μL reaction buffer + 20 μL substrate), an enzyme blank group (100 μL reaction buffer + 20 μL substrate), a sample group (80 μL sample + 20 μL enzyme + 20 μL substrate), and a sample blank group (80 μL sample + 100 μL reaction buffer + 20 μL substrate). The half-maximal inhibitory concentration (IC50) of the compound was also determined. 50The inhibition rate was calculated using Origin software. The formula for calculating the inhibition rate is: Inhibition rate = 1 - (Sample A - Sample A blank) / (Enzyme A activity - Enzyme A blank). The specific experimental results are shown in the table below.
[0112]
[0113] The test results showed that most of the compounds of the present invention exhibited significant α-glucosidase inhibitory activity in the α-glucosidase activity assay, especially compound 1n, which showed a high IC50 value against α-glucosidase. 50 The value reached 2.65±0.05μg / mL, demonstrating good potential for the prevention and / or treatment of type 2 diabetes.
[0114] In summary, this invention provides a quinoxaline-2(1H)-selenoketone derivative, its preparation method, and its application in the pharmaceutical field. This derivative is prepared by heating o-phenylenediamine, aryl ethyl ketone, and selenium powder in an organic solvent. The reaction requires no metal catalyst or oxidant, is simple to operate, and yields a high amount of product. The resulting compound exhibits significant inhibitory activity against α-glucosidase, demonstrating potential in the prevention and treatment of type II diabetes.
[0115] Any aspects of this invention not described in detail are well-known to those skilled in the art.
[0116] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within the present invention.
Claims
1. A quinoxaline-2(1H)-selenophenone derivative, characterized in that: The structural formula of the quinoxaline-2(1H)-selenophenone derivative is as follows: Wherein, substituent R is alkyl, alkoxy, halogen or phenyl, and Ar is phenyl, naphthyl, pyridyl, thiophene, or phenyl substituted with one or more substituents, wherein the substituent is alkyl, alkoxy, halogen, nitro, trifluoromethyl, ester or cyano.
2. The method for preparing a quinoxaline-2(1H)-selenophenone derivative according to claim 1, characterized in that, The preparation method is as follows: using o-phenylenediamine as shown in formula (I), aryl ethyl ketone as shown in formula (II), and selenium powder as shown in formula (III) as raw materials in an organic solvent, and using TMSCN as a reaction promoter, the reaction is carried out under certain temperature conditions to obtain the quinoxaline-2(1H)-selenoketone compound shown in formula (IV). The reaction equation is shown below: 。 3. The method for preparing a quinoxaline-2(1H)-selenophenone derivative according to claim 2, characterized in that, The structure of o-phenylenediamine is The structure of aryl ethyl ketone is ; Wherein, substituent R is alkyl, alkoxy, halogen or phenyl, and Ar is phenyl, naphthyl, pyridyl, thiophene, or phenyl substituted with one or more substituents, wherein the substituent is alkyl, alkoxy, halogen, nitro, trifluoromethyl, ester or cyano.
4. The method for preparing a quinoxaline-2(1H)-selenophenone derivative according to claim 2, characterized in that, The molar ratio of o-phenylenediamine (I), aryl ethyl ketone (II), and selenium powder (III) is 1.2:1:(1-2).
5. The method for preparing a quinoxaline-2(1H)-selenophenone derivative according to claim 2, characterized in that, The organic solvent is selected from one or more of dimethyl sulfoxide, N,N-dimethylformamide, xylene, and N-methylpyrrolidone.
6. The method for preparing a quinoxaline-2(1H)-selenophenone derivative according to claim 2, characterized in that, The reaction was at 120 o The reaction is carried out under heating and stirring for 8 to 16 hours.
7. The method for preparing a quinoxaline-2(1H)-selenophenone derivative according to claim 2, characterized in that, After the reaction was completed, the reaction solution was cooled to room temperature, filtered to remove residual selenium powder, extracted with dichloromethane, the organic phase was separated, dried with anhydrous sodium sulfate, concentrated under reduced pressure, and the desired product was separated by column chromatography; a dichloromethane / methanol mixture was used as the eluent, wherein the volume ratio of dichloromethane to methanol was 100 to 30:
1.
8. A pharmaceutical composition, characterized in that, The pharmaceutical composition comprises a quinoxaline-2(1H)-selenophenone derivative prepared by the method according to any one of claims 2-7, a medically acceptable salt, solvate or hydrate thereof, and a pharmaceutically acceptable carrier or excipient.
9. Use of the pharmaceutical composition of claim 8 in the preparation of a medicament for the prevention and / or treatment of type II diabetes.
10. The application according to claim 9, characterized in that, For the prevention and / or treatment of type 2 diabetes, the pharmaceutical composition has α-glucosidase inhibitory activity.