Design, synthesis and structure-activity relationships (SARs) studies of novel 4-substituted-2-amino-pyrido[3,4-d]pyrimidin-8(7H)-one analogs as potential antitumor agents

ORGN 691

Linyi Wei, weil3@mail.nih.gov, Laboratory of Synthetic Chemistry, National Cancer Institute, SAIC-Frederick, 1050 Boyles Street, Frederick, MD 21702 and Sanjay V. Malhotra, malhotrasa@mail.nih.gov, Laboratory of Synthetic Chemistry, National Cancer Institute - Frederick, SAIC-Frederick, 1050 Boyles Street, Frederick, MD 21702.
Novel 4-substituted-2-amino-pyrido[3,4-d]pyrimidin-8(7H)-one analogs were designed as potential serine/threonine or tyrosine kinase inhibitors based upon the publicly available X-ray crystal structures and associated molecular modeling studies. These new compounds contain a core scaffold with hydrogen bond acceptor/donor properties known to be important for kinase binding and can be synthesized efficiently in moderate to excellent yields. In the preliminary studies, these compounds are screened against a kinase panel as well as other cancer-related biological targets/applications. A structure-activity relationships (SARs) study was also explored to facilitate the further development of this new compound class. Results of these studies will be presented.