| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1363363 | Bioorganic & Medicinal Chemistry Letters | 2010 | 5 Pages |
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. Compound 30 was advanced to a mouse liver PD assay, where it showed dose-dependent inhibition of AKT activity, as measured by the inhibition of phospho-PRAS40.
Graphical abstractThe development of a series of potent AKT1 inhibitors is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Qingping Zeng, Matthew P. Bourbeau, G. Erich Wohlhieter, Guomin Yao, Holger Monenschein, James T. Rider, Matthew R. Lee, Shiwen Zhang, Julie Lofgren, Daniel Freeman, Chun Li, Elizabeth Tominey, Xin Huang, Douglas Hoffman, Harvey Yamane, Andrew S. Tasker,