Discovery and evaluation of 3-(5-thien-3-ylpyridin-3-yl)-1H-indoles as a novel class of KDR kinase inhibitors

Abstract

We have discovered 3-(5-thien-3-ylpyridin-3-yl)-1H-indoles as potent inhibitors of KDR kinase activity. This communication details the evolution of this novel class from a potent screening lead of vastly different structure with an emphasis on structural modifications that retained activity and provided improvements in key physical properties. The synthesis and in-depth evaluation of these inhibitors are described.