Design and evaluation of a series of pyrazolopyrimidines as p70S6K inhibitors

详细信息	查看全文 | 推荐本文 |

• 作者：Joerg Bussenius ; ^{jbusseni@exelixis.com} ; Neel K. Anand ; Charles M. Blazey ; Owen J. Bowles ; Lynne Canne Bannen ; Diva S.-M. Chan ; Baili Chen ; Erick W. Co ; Simona Costanzo ; Steven C. DeFina ; Larisa Dubenko ; Stefan Engst ; Maurizio Franzini ; Ping Huang ; Vasu Jammalamadaka ; Richard G. Khoury ; Moon H. Kim ; Rhett R. Klein ; Douglas Laird ; Donna T. Le ; Morrison B. Mac ; David J. Matthews ; David Markby ; Nicole Miller ; John M. Nuss ; Jason J. Parks ; Tsze H. Tsang ; Amy L. Tsuhako ; Yong Wang ; Wei Xu ; Kenneth D. Rice
• 关键词：p70S6K inhibitor ; Pyrazolopyrimidine ; PI3K pathway ; Cancer
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：15 March, 2012
• 卷：22
• 期：6
• 页码：2283-2286
• 文件大小：782 K

摘要

The 70-kDa ribosomal protein S6 kinase (p70S6K) is part of the PI3K/AKT/mTOR pathway and has been implicated in cancer. High throughput screening versus p70S6K led to the identification of aminopyrimidine g class="boldFont">3ag> as active inhibitor. Lead optimization of g class="boldFont">3ag> resulted in highly potent, selective, and orally bioavailable pyrazolopyrimidines. In this manuscript we report the structure-activity relationship of this series and pharmacokinetic, pharmacodynamic, and efficacy data of the lead compound g class="boldFont">13cg>.