1.
J Med Chem
; 51(20): 6259-62, 2008 Oct 23.
Artículo
en Inglés
| MEDLINE
| ID: mdl-18811140
RESUMEN
A high-throughput screen at 100 microM inhibitor concentration for the BACE-1 enzyme revealed a novel spiropiperidine iminohydantoin aspartyl protease inhibitor template. An X-ray cocrystal structure with BACE-1 revealed a novel mode of binding whereby the inhibitor interacts with the catalytic aspartates via bridging water molecules. Using the crystal structure as a guide, potent compounds with good brain penetration were designed.