Synthesis and antidiabetic activity evaluation of benzopyrimidine derivatives
10.11665/j.issn.1000-5048.2023041701
- VernacularTitle:苯并嘧啶衍生物的合成和抗糖尿病活性评价
- Author:
Yuantao XU
1
;
Jundong WANG
;
Li GUAN
;
Ning ZHAO
;
Weize LI
Author Information
1. 陕西盘龙药业集团股份有限公司
- Publication Type:Journal Article
- Keywords:
diabetes;
thioredoxin interaction protein inhibitor;
benzopyrimidine derivative;
cell protection
- From:
Journal of China Pharmaceutical University
2023;54(5):569-576
- CountryChina
- Language:Chinese
-
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.
