discovery and structure-activity studies of a novel series of pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors

Abstract The inhibition of tyrosine kinase-mediated signal transduction pathways represents a therapeutic approach to the intervention of proliferative diseases such as cancer, atherosclerosis, and restenosis. A novel series of pyrido[2,3- d ]pyrimidine inhibitors of the PDGFr, bFGFr, and c-Src tyrosine kinases was developed from compound library screening and lead optimization. 1 In addition, highly selective inhibitors of the FGFr tyrosine kinase were also discovered and developed from this novel series of pyrido[2,3- d ]pyrimidines. The syntheses, biological evaluation, and structure-activity relationships of this series are reported.