Author/Authors :
Stephen F. Brady، نويسنده , , Satendra Singh، نويسنده , , Ming-Chih Crouthamel، نويسنده , , M.Katharine Holloway، نويسنده , , Craig A. Coburn، نويسنده , , Victor M. Garsky، نويسنده , , Michael Bogusky، نويسنده , , Michael W. Pennington، نويسنده , , Joseph P. Vacca، نويسنده , , Daria Hazuda، نويسنده , , Ming-Tain Lai، نويسنده ,
Abstract :
An effective approach for enhancing the selectivity of β-site amyloid precursor protein cleaving enzyme (BACE 1) inhibitors is developed based on the unique features of the S1′ pocket of the enzyme. A series of low molecular weight (<600) compounds were synthesized with different moieties at the P1′ position. The selectivity of BACE 1 inhibitors versus cathepsin D and renin was enhanced 120-fold by replacing the hydrophobic propyl group with a hydrophilic propionic acid group.
