Scott Harried

TL;DR: This work identified a series of benzodioxolane analogues that possessed improved metabolic stability and increased oral bioavailability and identified an inhibitor which demonstrated robust and sustained reduction of CNS β-amyloid (Aβ) in Sprague-Dawley rats following oral administration.

TL;DR: Modifications of the P1-phenyl ring of the hydroxyethylamine series are described to afford potent, dual BACE1/CYP 3A4 inhibitors which demonstrate improved penetration into the CNS.

TL;DR: This disclosure focuses on medicinal-chemistry efforts to improve the druglike properties of initial leads, particularly removal of CYP3A4-induction liability and improvement of pharmacokinetic properties.

TL;DR: Further optimization leading to the discovery of inhibitor 15 as an orally available and highly efficacious BACE1 inhibitor that robustly reduces CSF and brain Aβ levels in both rats and nonhuman primates is reported.

TL;DR: In this article, the authors describe novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like.