Pike K.G.,Astrazeneca |
Malagu K.,Former Employees of KuDOS Pharmaceuticals Ltd. |
Hummersone M.G.,Former Employees of KuDOS Pharmaceuticals Ltd. |
Menear K.A.,Former Employees of KuDOS Pharmaceuticals Ltd. |
And 6 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2013
The optimization of a potent and highly selective series of dual mTORC1 and mTORC2 inhibitors is described. An initial focus on improving cellular potency whilst maintaining or improving other key parameters, such as aqueous solubility and margins over hERG IC50, led to the discovery of the clinical candidate AZD8055 (14). Further optimization, particularly aimed at reducing the rate of metabolism in human hepatocyte incubations, resulted in the discovery of the clinical candidate AZD2014 (21). © 2012 Elsevier Ltd. All rights reserved.