Discovery of dibenzo[c,f][2,7]naphthyridines as potent and selective 3-phosphoinositide-dependent kinase-1 inhibitors.
Basic Information
ID: ALA1138235
Journal: J Med Chem
Title: Discovery of dibenzo[c,f][2,7]naphthyridines as potent and selective 3-phosphoinositide-dependent kinase-1 inhibitors.
Authors: Gopalsamy A, Shi M, Boschelli DH, Williamson R, Olland A, Hu Y, Krishnamurthy G, Han X, Arndt K, Guo B.
Abstract: 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.
CiteXplore: 17941624
DOI: 10.1021/jm070851i
Patent ID: ┄