2. Academic Validation
  3. Phthalazinone pyrazoles as potent, selective, and orally bioavailable inhibitors of Aurora-A kinase

Phthalazinone pyrazoles as potent, selective, and orally bioavailable inhibitors of Aurora-A kinase

  • J Med Chem. 2011 Jan 13;54(1):312-9. doi: 10.1021/jm101346r.
Michael E Prime 1,  Stephen M Courtney,  Frederick A Brookfield,  Richard W Marston,  Victoria Walker,  Justin Warne,  Andrew E Boyd,  Norman A Kairies,  Wolfgang von der Saal,  Anja Limberg,  Guy Georges,  Richard A Engh,  Bernhard Goller,  Petra Rueger,  Matthias Rueth
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Affiliation

PMID: 21128645 DOI: 10.1021/jm101346r
Abstract

The inhibition of Aurora kinases in order to arrest mitosis and subsequently inhibit tumor growth via Apoptosis of proliferating cells has generated significant discussion within the literature. We report a novel class of Aurora Kinase inhibitors based upon a phthalazinone pyrazole scaffold. The development of the phthalazinone template resulted in a potent Aurora-A selective series of compounds (typically >1000-fold selectivity over Aurora-B) that display good pharmacological profiles with significantly improved oral bioavailability compared to the well studied Aurora inhibitor VX-680.

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