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Discovery of a highly potent orally bioavailable imidazo-[1, 2-a]pyrazine Aurora inhibitor
Tao Yu1, Yonglian Zhang1, Angela D Kerekes1
1Department of Chemical Research, MRL 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Abstract:
Imidazo-[1, 2-a]pyrazine 1 is a potent inhibitor of Aurora A and B kinase in vitro and is effective in in vivo tumor models, but has poor oral bioavailbility and is unsuitable for oral dosing. We describe herein our effort to improve oral exposure in this class, resulting ultimately in the identification of a potent Aurora inhibitor 16, which exhibited good drug exposure levels across species upon oral dosing, and showed excellent in vivo efficacy in a mouse xenograft tumor model when dosed orally.
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