Discovery of dibenzo[c,f][2,7]naphthyridines as potent and selective 3-phosphoinositide-dependent kinase-1 inhibitors.
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Gopalsamy A, Shi M, Boschelli DH, Williamson R, Olland A, Hu Y, Krishnamurthy G, Han X, Arndt K, Guo B
Discovery of dibenzo[c,f][2,7]naphthyridines as potent and selective 3-phosphoinositide-dependent kinase-1 inhibitors.
J Med Chem. 2007 Nov 15;50(23):5547-9. Epub 2007 Oct 17.
- PubMed ID
- 17941624 [ View in PubMed]
- 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.