DISCOVERY AND STRUCTURE-ACTIVITY STUDIES OF A NOVEL SERIES OF PYRIDO[2,3-D]PYRIMIDINE TYROSINE KINASE INHIBITORS

The inhibition of tyrosine kinase-mediated signal transduction pathway s represents a therapeutic approach to the intervention of proliferati ve diseases such as cancer, atherosclerosis, and restenosis. A novel s eries of pyrido[2,3-d]pyrimidine inhibitors of the PDGFr, bFGFr, and c -Src tyrosine kinases was developed from compound library screening an d lead optimization.(1) In addition, highly selective inhibitors of th e FGFr tyrosine kinase were also discovered and developed from this no vel series of pyrido[2,3-d]pyrimidines. The syntheses, biological eval uation, and structure-activity relationships of this series are report ed. (C) 1997 Elsevier Science Ltd.