A series of novel tricyclic pyrimido[4,5-b][1,4]benzothiazepines were synthesized and evaluated against a panel of kinases for possible inhibitory activity. It was discovered that several compounds within this class exhibit potent (nanomolar IC50) and selective activity against p38 alpha kinase. Inhibiton of this particular kinase target has the potential to treat a number of disease indications, including cancer. This presentation will describe the structures and the synthesis of this novel class of compounds. In addition, the p38 alpha activity of the compounds will be discussed along with an evaluation of the structure-activity relationships that have been developed within the series.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA