2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles
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- 作者：Hong Lin ; Dennis S. Yamashita ; Jin Zeng ; Ren Xie ; Sharad Verma ; Juan I. Luengo ; Nelson Rhodes ; Shuyun Zhang ; Kimberly A. Robell ; Anthony E. Choudhry ; Zhihong Lai ; Rakesh Kumar ; Elisabeth A. Minthorn
- 关键词：AKT kinase inhibitors ; Selectivity ; Azaindazole
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2010
- 出版时间：15 January 2010
- 年：2010
- 卷：20
- 期：2
- 页码：679-683
- 全文大小：431 K
文摘
A novel series of AKT inhibitors containing 2,3,5-trisubstituted pyridines with novel azaindazoles as hinge binding elements are described. Among these, the 4,7-diazaindazole compound 2c has improved drug-like properties and kinase selectivity than those of indazole 1, and displays greater than 80 % inhibition of GSK3β phosphorylation in a BT474 tumor xenograft model in mice.