Synthesis and Biological Evaluation of Substituted 3-anilino-quinolin-2(1H)-ones as PDK1 Inhibitors

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O'Brien, N. J., Brzozowski, M., Wilson, D. J., Deady, L. W., & Abbott, B. M. (2014). Synthesis and biological evaluation of substituted 3-anilino-quinolin-2(1H)-ones as PDK1 inhibitors. Bioorganic and Medicinal Chemistry, 22(14), 3781-3790. doi:10.1016/j.bmc.2014.04.037



030701 Quantum Chemistry


PDK1 is an important regulator of the PI3K/Akt pathway, which has been found frequently activated in a large number of human cancers. Herein we described the preparation of novel substituted 3-anilino-quinolin-2(1H)-ones as PDK1 inhibitors. The synthesis is based around a Buchwald–Hartwig cross-coupling of various 3-bromo-6-substituted-quinolin-2(1H)-ones with three different functionalised anilines. The modular nature of the designed synthesis allowed access to a series of novel inhibitors through derivatisation of a late-stage intermediate. All compounds were screened against isolated PDK1 enzyme, with modest inhibition observed.


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At the time of writing David Wilson was affiliated with Avondale College as a Conjoint Lecturer.