Novel 2-phenoxypyrido[3,2-b]pyrazin-3(4H)-one derivatives as potent and selective aldose reductase inhibitors with antioxidant activity

Journal of Enzyme Inhibition and Medicinal Chemistry

Changjin Zhu¹  Hongxing Ma²  Gang Qi²  Zhongfei Han³  Xin Hao⁴ 

[1] Department of Applied Chemistry, Beijing Institute of Technology, Beijing, PR China;Faculty of Chemistry and Chemical Engineering, Yancheng Institute of Technology, Yancheng, PR Chin;Faculty of Chemistry and Chemical Engineering, Yancheng Institute of Technology, Yancheng, PR Chin;Department of Applied Chemistry, Beijing Institute of Technology, Beijing, PR China;The State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, PR China;Department of Applied Chemistry, Beijing Institute of Technology, Beijing, PR China;

关键词: Aldose reductase inhibitor;    antioxidant activity;    b;   

DOI  :  10.1080/14756366.2019.1643336

来源: publisher

【 摘 要 】

To develop multifunctional aldose reductase (AKR1B1) inhibitors for anti-diabetic complications, a novel series of 2-phenoxypyrido[3,2-b]pyrazin-3(4H)-one derivatives were designed and synthesised. Most of the derivatives were found to be potent and selective against AKR1B1, and 2-(7-chloro-2-(3,5-dihydroxyphenoxy)-3-oxopyrido[3,2-b]pyrazin-4(3H)-yl) acetic acid (4k) was the most active with an IC50 value of 0.023 µM. Moreover, it was encouraging to find that some derivatives showed strong antioxidant activity, and among them, the phenolic 3,5-dihydroxyl compound 4l with 7-bromo in the core structure was proved to be the most potent, even comparable to that of the well-known antioxidant Trolox. Thus the results suggested success in the construction of potent and selective AKR1B1 inhibitors with antioxidant activity.

【 授权许可】

CC BY