Document Report Card

ID: ALA1145451

Journal: J Med Chem

Title: Discovery of isonicotinamide derived beta-secretase inhibitors: in vivo reduction of beta-amyloid.

Authors: Stanton MG, Stauffer SR, Gregro AR, Steinbeiser M, Nantermet P, Sankaranarayanan S, Price EA, Wu G, Crouthamel MC, Ellis J, Lai MT, Espeseth AS, Shi XP, Jin L, Colussi D, Pietrak B, Huang Q, Xu M, Simon AJ, Graham SL, Vacca JP, Selnick H.

Abstract: beta-Secretase inhibition offers an exciting opportunity for therapeutic intervention in the progression of Alzheimer's disease. A series of isonicotinamides derived from traditional aspartyl protease transition state isostere inhibitors has been optimized to yield low nanomolar inhibitors with sufficient penetration across the blood-brain barrier to demonstrate beta-amyloid lowering in a murine model.

CiteXplore: 17583334

DOI: 10.1021/jm070272d