Document Report Card

ID: ALA1138824

Journal: J Med Chem

Title: Design and synthesis of hydroxyethylene-based peptidomimetic inhibitors of human beta-secretase.

Authors: Hom RK, Gailunas AF, Mamo S, Fang LY, Tung JS, Walker DE, Davis D, Thorsett ED, Jewett NE, Moon JB, John V.

Abstract: The hydroxyethylene (HE) transition state isostere was developed as a scaffold to provide potent, small molecule inhibitors of human beta-secretase (BACE). The previous work on the statine series proved critical to the discovery of HE structure-activity relationships. Compound 20 with the N-terminal isophthalamide proved to be the most potent HE inhibitor (IC(50) = 30 nM) toward BACE. Unlike the statine series, we identified HE inhibitors without carboxylic acids on the C terminus, leading to enhanced cell penetration and making them attractive candidates for further drug development in Alzheimer's disease.

CiteXplore: 14695829

DOI: 10.1021/jm0304008