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Bioorg Med Chem Lett. 2008 Jan 1;18(1):418-22. Epub 2007 Oct 18.

Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor.

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  • 1Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.


Based on a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by 1a and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings.

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