Author/Authors :
William F. Fobare، نويسنده , , William R. Solvibile Jr.، نويسنده , , Albert J. Robichaud، نويسنده , , Michael S. Malamas، نويسنده , , Eric Manas، نويسنده , , Jim Turner، نويسنده , , Yun Hu، نويسنده , , Erik Wagner، نويسنده , , Rajiv Chopra، نويسنده , , Rebecca Cowling، نويسنده , , Guixan Jin، نويسنده , , Jonathan Bard، نويسنده ,
Abstract :
A series of thiophene-substituted acylguanidines were designed from a pyrrole substituted acylguanidine HTS lead. This template allowed a greater flexibility, through differential Suzuki couplings, to explore the binding site of BACE1 and to enhance the inhibitory potencies. This exploration provided a 25-fold enhancement in potency to yield compound 10a, which was 150 nM in a BACE1 FRET assay.
Keywords :
Beta-secretase , BACE1 , Aspartyl protease , Acylguanidine
