Discovery of N-phenyl-4-(thiazol-5-yl) pyrimidin-2-amine aurora kinase inhibitors

…, C McInnes, C Meades, M Mezna, A Plater…

Index: Wang, Shudong; Midgley, Carol A.; Scaerou, Frederic; Grabarek, Joanna B.; Griffiths, Gary; Jackson, Wayne; Kontopidis, George; McClue, Steven J.; McInnes, Campbell; Meades, Christopher; Mezna, Mokdad; Plater, Andy; Stuart, Iain; Thomas, Mark P.; Wood, Gavin; Clarke, Rosemary G.; Blake, David G.; Zheleva, Daniella I.; Lane, David P.; Jackson, Robert C.; Glover, David M.; Fischer, Peter M. Journal of Medicinal Chemistry, 2010 , vol. 53, # 11 p. 4367 - 4378

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Citation Number: 52

Abstract

Through cell-based screening of our kinase-directed compound collection, we discovered that a subset of N-phenyl-4-(thiazol-5-yl) pyrimidin-2-amines were potent cytotoxic agents against cancer cell lines, suppressed mitotic histone H3 phosphorylation, and caused aberrant mitotic phenotypes. It was subsequently established that these compounds were in fact potent inhibitors of aurora A and B kinases. It was shown that potency and selectivity ...