Structure–activity relationships studies of quinoxalinone derivatives as aldose reductase inhibitors

• DOI: 10.1016/j.ejmech.2014.04.047
• Publication Date: 2014-04-21T22:30:44Z
• Authors: Saghir Hussain; Shagufta Parveen; Xin Hao; Shuzhen Zhang; Wei Wang; Xiangyu Qin; Yanchun Yang; Xin Chen; Shaojuan Zhu; Changjin Zhu; Bing Ma
• Keywords: IC50; Structure–activity relationship; Aldehyde Reductase; Side chain

Novel quinoxalinone derivatives were synthesized and tested for their inhibitory activity against aldose reductase. Among them, N1-acetate derivatives had significant activity in a range of IC50 values from low micromolar to submicromolar, and compound 15a bearing a C3-phenethyl side chain was identified as the most potent inhibitor with an IC50 value of 0.143 μM. The structure-activity studies suggested that both C3-phenethyl and C6-NO2 groups play an important role in enhancing the activity and selectivity of the quinoxalinone based inhibitors.