Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents

作者：Wang, Chao; Zhang, Hao; Xu, Fengrong; Niu, Yan^*; Wu, Yun; Wang, Xin; Peng, Yihong; Sun, Jing; Liang, Lei; Xu, Ping

来源：Molecules, 2013, 18(5): 6057-6091.

DOI：10.3390/molecules18056057

• MEK1 inhibitor
• coumarin
• antiviral

In order to find novel antiviral agents, a series of allosteric MEK1 inhibitors were designed and synthesized. Based on docking results, multiple optimizations were made on the coumarin scaffold. Some of the derivatives showed excellent MEK1 binding affinity in the appropriate enzymatic assays and displayed obvious inhibitory effects on the ERK pathway in a cellular assay. These compounds also significantly inhibited virus (EV71) replication in HEK293 and RD cells. Several compounds showed potential as agents for the treatment of viral infective diseases, with the most potent compound 18 showing an IC50 value of 54.57 nM in the MEK1 binding assay.

• 出版日期2013-5
• 单位北京大学; 天然药物与仿生药物国家重点实验室