Discovery of isonicotinamide derived beta-secretase inhibitors: In vivo reduction of beta-amyloid

作者:Stanton Matthew G*; Stauffer Shaun R; Gregro Alison R; Steinbeiser Melissa; Nantermet Philippe; Sankaranarayanan Sethu; Price Eric A; Wu Guoxin; Crouthamel Ming Chih; Ellis Joan; Lai Ming Tain; Espeseth Amy S; Shi Xiao Ping; Jin Lixia; Colussi Dennis; Pietrak Beth; Huang Qian; Xu Min; Simon Adam J; Graham Samuel L; Vacca Joseph P; Selnick Harold
来源:Journal of Medicinal Chemistry, 2007, 50(15): 3431-3433.
DOI:10.1021/jm070272d

摘要

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.

  • 出版日期2007-7-26