Pyridyl aminothiazoles as potent Chk1 inhibitors: Optimization of cellular activity

Translation of significant biochemical activity of pyridyl aminothiazole class of Chk1 inhibitors into functional CEA potency required analysis and adjustment of both physical properties and kinase selectivity profile of the series. The steps toward optimization of cellular potency included elimination of CDK7 activity, reduction of molecular weight and polar surface area and increase in lipophilicity of the molecules in the series.

The optimization of selectivity and physical properties of pyridyl aminothiazole series of Chk1 inhibitors aimed at improving cellular activity levels is described.Figure optionsDownload as PowerPoint slide