N3-Arylmalonamides: A new series of thieno[3,2-b]pyridine based inhibitors of c-Met and VEGFR2 tyrosine kinases

A series of thieno[3,2-b]pyridine inhibitors of the receptor tyrosine kinases c-Met and VEGRF2, bearing the N3-arylmalonamides functionality, is described. A family of thieno[3,2-b]pyridine based small molecule inhibitors of c-Met and VEGFR2 were designed based on lead structure 2. These compounds were shown to have IC50 values in the low nanomolar range in vitro and were efficacious in human tumor xenograft models in mice in vivo.