Thienopyridine urea inhibitors of KDR kinase

A series of substituted thienopyridine ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 2, are potent inhibitors of KDR (<10 nM) in both enzymatic and cellular assays. Further characterization of inhibitor 2 indicated that this analog possessed excellent in vivo potency (ED50 2.1 mg/kg) as measured in an estradiol-induced mouse uterine edema model.

Graphical abstractThe evaluation of KDR kinase inhibitor 2 (IC50 = 9 nM) and related analogs is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide