Synthesis and Biological Evaluation of Substituted 3-anilino-quinolin-2(1H)-ones as PDK1 Inhibitors
This article was originally published as:
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
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.
O'Brien, Nathan J.; Brzozowski, Martin; Wilson, David J.; Deady, Leslie W.; and Abbott, Belinda M., "Synthesis and Biological Evaluation of Substituted 3-anilino-quinolin-2(1H)-ones as PDK1 Inhibitors" (2014). Science and Mathematics Papers and Journal Articles. 62.