2, 3, 5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles

…, R Xie, S Verma, JI Luengo, N Rhodes, S Zhang…

Index: Lin, Hong; Yamashita, Dennis S.; Zeng, Jin; Xie, Ren; Verma, Sharad; Luengo, Juan I.; Rhodes, Nelson; Zhang, Shuyun; Robell, Kimberly A.; Choudhry, Anthony E.; Lai, Zhihong; Kumar, Rakesh; Minthorn, Elisabeth A.; Brown, Kristin K.; Heerding, Dirk A. Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 2 p. 679 - 683

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Citation Number: 11

Abstract

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.