2-Aminothiadiazole inhibitors of AKT1 as potential cancer therapeutics

Q Zeng, MP Bourbeau, GE Wohlhieter, G Yao…

Index: Zeng, Qingping; Bourbeau, Matthew P.; Wohlhieter, G. Erich; Yao, Guomin; Monenschein, Holger; Rider, James T.; Lee, Matthew R.; Zhang, Shiwen; Lofgren, Julie; Freeman, Daniel; Li, Chun; Tominey, Elizabeth; Huang, Xin; Hoffman, Douglas; Yamane, Harvey; Tasker, Andrew S.; Dominguez, Celia; Viswanadhan, Vellarkad N.; Hungate, Randall; Zhang, Xiaoling Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 5 p. 1652 - 1656

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Citation Number: 24

Abstract

A series of 2-aminothiadiazole of inhibitors of AKT1 is described. SAR relationships are discussed, along with selectivity for protein kinase A (PKA) and cyclin-dependent kinase 2 (CDK2). Moderate selectivity observed in several compounds for AKT1 versus PKA is rationalized by X-ray crystallographic analysis. Key compounds showed activity in cellular assays measuring phosphorylation of two AKT substrates, PRAS40 and FKHRL1. ...