Browsing by Author "Deady, Leslie W."
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Item Synthesis and Biological Evaluation of Substituted 2-anilino-7H-pyrrolopyrimidines as PDK1 Inhibitors(2014-05-21) Abbott, Belinda M.; Deady, Leslie W.; Wilson, David J.; Brzozowski, Martin; O'Brien, Nathan J.An efficient and scalable route for a series of novel substituted 2-anilino-7H-pyrrolopyrimidine compounds as potential inhibitors of PDK1, an important regulator of the PI3K/Akt pathway that is dysregulated in many cancers, was developed and is described. The synthetic strategy was designed around Suzuki and BuchwaldeHartwig cross-couplings of a boronate fragment and various customised anilines sequentially with 2,4-dichloro-7-tosyl-7H-pyrrolopyrimidine. All fragments were constructed separately and cross-coupled to provide access to a range of novel compounds. Biological evaluation of these was undertaken, with modest inhibition observed.
Item Synthesis and Biological Evaluation of Substituted 3-anilino-quinolin-2(1H)-ones as PDK1 Inhibitors(2014-07-15) Abbott, Belinda M.; Deady, Leslie W.; Wilson, David J.; Brzozowski, Martin; O'Brien, Nathan J.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.