Discovery of novel morpholino-quinoxalines as PI3Kα inhibitors by pharmacophore-based screening

作者：Wu, Peng; Su, Yi; Liu, Xiaowen; Yan, Jingying; Ye, Yong; Zhang, Lei; Xu, Jianchao; Weng, Shaoyu; Li, Yani; Liu, Tao; Dong, Xiaowu; Sun, Maotang; Yang, Bo; He, Qiaojun; Hu, Yongzhou^*

来源：Medchemcomm, 2012, 3(6): 659-662.

DOI：10.1039/c2md00255h

• BIOLOGICAL EVALUATION
• CANCER
• PI3K
• MUTATIONS
• 3-KINASE
• THERAPY
• PATHWAY
• KINASE
• TARGET

A pharmacophore model of PI3K alpha inhibitors was built using the DiscoveryStudio 2.0 package. Pharmacophore-based screening (PBS) retrieved a series of novel morpholino-quinoxalines as PI3K alpha inhibitors, as exemplified by 1a (PI3K alpha IC50: 0.44 mu M). All target compounds showed good in vitro cytotoxicity against tested human cell lines. A pharmacophore mapping analysis and docking study indicated that both the morpholino group and the sulfonyl group contributed significantly to the potent PI3K alpha inhibitory activity and cytotoxicity of the compounds.

• 出版日期2012-6
• 单位浙江大学