苯并嘧啶衍生物的合成和抗糖尿病活性评价

徐远涛; 王军栋; 关丽; 赵宁; 李伟泽

doi:10.11665/j.issn.1000-5048.2023041701

苯并嘧啶衍生物的合成和抗糖尿病活性评价

1.
陕西盘龙药业集团股份有限公司，柞水 714000
2.
山东省烟台市食品药品检验检测中心，烟台 264000
3.
西安医学院药学院，西安 710021

基金项目: 国家自然科学基金资助项目（No.82004075）；陕西省科技厅资助项目（No.2023-JC-QN-0827）；陕西高校青年创新团队建设资助项目（陕教［2019］90号）；西安医学院科技创新团队配套项目（No.2021TDPT04）

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出版历程
- 收稿日期: 2023-04-16
- 修回日期: 2023-10-17
- 刊出日期: 2023-10-24

Synthesis and antidiabetic activity evaluation of benzopyrimidine derivatives

1.
Shaanxi Panlong Pharmaceutical Group Co., Ltd., Zhashui 714000
2.
Shandong Yantai Food and Drug Inspection and Testing Center, Yantai 264000
3.
College of Pharmacy, Xi'an Medical University, Xi'an 710021, China

Funds: This study was supported by the National Natural Science Foundation of China (No.82004075); the Project of Shaanxi Provincial Department of Science and Technology (No.2023-JC-QN-0827); the Youth Innovation Team Construction Project for Universities in Shaanxi Province (Shaanxi Education [2019] No.90); and the Science and Technology Innovation Team Project of Xi’an Medical University (No.2021TDPT04)

摘要

摘要: 硫氧还蛋白相互作用蛋白(thioredoxin-interacting protein, TXNIP)主要调节胰岛β细胞中葡萄糖的稳态，是治疗糖尿病的新颖靶点。本研究以4-羟基苯并嘧啶为原料，通过不同长度的碳链，引入吡唑、甲基哌嗪、咪唑、吗啡啉等4种含氮杂环，设计合成靶向TXNIP的苯并嘧啶骨架拼合含氮杂环的衍生物，并考察化合物对棕榈酸(palmitate acid, PA)刺激的胰岛β细胞损伤的保护作用。共设计合成20个苯并嘧啶衍生物，结构经¹H NMR、ESI-MS确证；药理活性表明大部分化合物对胰岛β细胞有保护作用，其中化合物C-1、C-2、C-4、D-2保护作用较强，相较PA模型组细胞活力为38.3%，这4个化合物细胞活力高于70%，其中化合物D-2细胞活力最高，达到87.2%；化合物D-2可以作为潜在的抗糖尿病新化学实体。
- 糖尿病 /
- 硫氧还蛋白相互作用蛋白抑制剂 /
- 苯并嘧啶衍生物 /
- 细胞保护
Abstract: Thioredoxin-interacting protein (TXNIP), which mainly regulates glucose homeostasis in pancreatic β cells, is a novel target in the treatment of diabetes.In this study, 4-hydroxybenzopyrimidine was used as the raw material, four nitrogen-containing rings (imidazole, methylpiperazine, pyrazole, morpholine) were introduced, benzopyrimidine skeleton with nitrogen-containing rings derivatives targeting TXNIP was designed and synthesized, and the protective effect of compounds on palmitic acid-stimulated islet β cells was investigated.A total of 20 benzopyrimidine derivatives were designed and synthesized, and the structures were confirmed by ¹H NMR and ESI-MS.Pharmacological studies showed that most of the compounds exhibited protective effects on islet β cells, with better axtivity for compounds C-1, C-2, C-4 and D-2 (cell survival rate > 70%) compared with PA model group (38.3%), Among the four compounds, D-2 had the highest activity of 87.2%, so it could become a potential new anti-diabetic chemical entity.
- diabetes /
- thioredoxin interaction protein inhibitor /
- benzopyrimidine derivative /
- cell protection

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参考文献(11)

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文章访问数: 135
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苯并嘧啶衍生物的合成和抗糖尿病活性评价

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出版历程

Synthesis and antidiabetic activity evaluation of benzopyrimidine derivatives

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出版历程

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