Pyridinylimidazole inhibitors of Tie2 kinase

This communication details the evolution of the screening lead SB-203580, a known CSBP/p38 kinase inhibitor, into a potent and selective Tie2 tyrosine kinase inhibitor. The optimized compound 5 showed efficacy in an in vivo model of angiogenesis and a MOPC-315 plasmacytoma xenograft model.

Graphical abstractThe synthesis and in-depth evaluation of compound 5, an inhibitor (IC50 = 250 nM) of Tie2 kinase, is described.Figure optionsDownload full-size imageDownload as PowerPoint slide