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  • Title: 2-anilino-4-aryl-8H-purine derivatives as inhibitors of PDK1.
    Author: Blanchard S, Soh CK, Lee CP, Poulsen A, Bonday Z, Goh KL, Goh KC, Goh MK, Pasha MK, Wang H, Williams M, Wood JM, Ethirajulu K, Dymock BW.
    Journal: Bioorg Med Chem Lett; 2012 Apr 15; 22(8):2880-4. PubMed ID: 22437109.
    Abstract:
    A series of 2-anilino substituted 4-aryl-8H-purines were prepared as potent inhibitors of PDK1, a serine-threonine kinase thought to play a role in the PI3K/Akt signaling pathway, a key mediator of cancer cell growth, survival and tumorigenesis. The synthesis, SAR and ADME properties of this series of compounds are discussed culminating in the discovery of compound 6 which possessed sub-micromolar cell proliferation activity and 65% oral bioavailability in mice.
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