Author/Authors :
Michael S. Malamas، نويسنده , , Keith Barnes، نويسنده , , Matthew Johnson، نويسنده , , Yu Hui، نويسنده , , Ping Zhou، نويسنده , , Jim Turner، نويسنده , , Yun Hu، نويسنده , , Erik Wagner، نويسنده , , Kristi Fan، نويسنده , , Rajiv Chopra، نويسنده , , Andrea Olland، نويسنده , , Jonathan Bard، نويسنده , , Menelas Pangalos، نويسنده , , Peter Reinhart، نويسنده , , Albert J. Robichaud، نويسنده ,
Abstract :
The identification of highly selective small molecule di-substituted pyridinyl aminohydantoins as β-secretase inhibitors is reported. The more potent and selective analogs demonstrate low nanomolar potency for the BACE1 enzyme as measured in a FRET assay, and exhibit comparable activity in a cell-based (ELISA) assay. In addition, these pyridine-aminohydantoins are highly selectivity (>500×) against the other structurally related aspartyl proteases BACE2, cathepsin D, pepsin and renin.
Keywords :
Alzheimer’s disease (AD) , BACE1 inhibitors , Aminohydantoins , ?-Amyloid peptide (A?)
