National Center for
3LPJ: Structure of BACE Bound to SCH743641
Bioorg. Med. Chem. Lett. (2010) 20 p.2837-2842
With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2' sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral Abeta(40) in transgenic mice with a single subcutaneous dose.