Discovery of Dibenzo[c,f][2,7]naphthyridines as Potent and Selective 3-Phosphoinositide-Depehdent Kinase-1 Inhibitors

摘要

With high-throughput screening,substituted dibenzo[c,f][2,7]-naphthyridine 1 was identified as a novel potent and selective phosphoinositide-dependent kinase-1(PDK-1)inhibitor.Various regions of the lead molecule were explored to understand the SAR requirement for this scaffold.The crystal structure of 1 with kinase domain of PDK-1 confirmed the binding in the active site.The key interaction of the molecule with the active site residues,observed SAR,and the biological profile are discussed in detail.