| Institution: | 1. Department of Chemical Research, MRL 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA;2. Department of Oncology, MRL 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA;3. Department of DMPK, MRL 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA;4. Department of Structural Chemistry, MRL 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA;5. Department of Chemical Research, MRL 320 Bent Street, Cambridge, MA 02141, USA;6. AMRI, 26 Corporate Circle, PO Box 15098, Albany, NY 12212, 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. |
