1374748-59-0Relevant articles and documents
An Efficient Synthesis of Quinoxalinone Derivatives as Potent Inhibitors of Aldose Reductase
Yang, Yanchun,Zhang, Shuzhen,Wu, Bobin,Ma, Mingming,Chen, Xin,Qin, Xiangyu,He, Minlan,Hussain, Saghir,Jing, Chaojun,Ma, Bing,Zhu, Changjin
, p. 823 - 835 (2012/07/17)
A novel and facile synthesis of quinoxalinone derivatives was developed in which a wide range of 3-chloroquinoxalin-2(1H)-ones as key intermediates can be generated chemo- and regioselectively in good yields from corresponding quinoxaline-2,3(1H,4H)-diones. This new protocol is arguably superior, as it allows the design and preparation of a variety of bioactive quinoxaline-based compounds, which are particularly effective in the treatment of diabetes and its complications. Through this procedure, a new class of quinoxalinone-based aldose reductase inhibitors were synthesized successfully. Most of the inhibitors, with an N1-acetic acid head group and a substituted C3-phenoxy side chain, proved to be potent and selective. Their IC50 values ranged from 11.4 to 74.8nM. Among them, 2-(3-(4-bromophenoxy)-7-fluoro-2-oxoquinoxalin-1(2H)-yl)acetic acid and 2-(6-bromo-3-(4-bromophenoxy)-2-oxoquinoxalin-1(2H)-yl)acetic acid were the most active. Structure-activity relationship and molecular docking studies highlighted the importance of the ether spacer in the C3-phenoxy side chains, and provided clear guidance on the contribution of substitutions both at the core structure and the side chain to activity.
