Structure-based design, synthesis and biological evaluation of diphenylmethylamine derivatives as novel Akt1 inhibitors
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- 作者：Tao Liu ; Wenhu Zhan ; Yanming Wang ; Liangren Zhang ; Bo Yang ; Xiaowu Dong ; Yongzhou Hu
- 关键词：Akt1 inhibitor ; Diphenylmethylamine ; Pharmacophore ; Molecular docking ; Anti-proliferative activity
- 刊名：European Journal of Medicinal Chemistry
- 出版年：12 February, 2014
- 年：2014
- 卷：73
- 期：Complete
- 页码：167-176
- 全文大小：1795 K
文摘
A series of diphenylmethylamine derivatives were rationally designed, synthesized and biologically evaluated. Most of them exhibited moderate to good Akt1 inhibitory activities, as well as promising anti-proliferative efficacy against cancer cell lines. Besides, molecular docking studies were carried out to probe their binding modes with Akt1. Further kinase selectivity studies of compound 22c were performed, indicating its excellent selectivity against Aurora A, Drak, IKK尾, GSK3尾, SYK and JAK2, and moderate selectivity against PKC and BRAF. Finally, a refined pharmacophore model was generated using the most active compounds 2, 12c and 22c via application of HipHop program.