Rueeger, Heinrich, Lueoend, Rainer Martin, Machauer, Rainer, Veenstra, Siem, Jacobson, Laura, Staufenbiel, Matthias, Desrayaud, Sandrine, Rondeau, Jean-Michel, Moebitz, Henrik and Neumann, Ulf (2013) Discovery of Cyclic Sulfoxide Hydroxyethylamines as Potent and Selective β-Site APP-Cleaving Enzyme 1 (BACE1) Inhibitors: Structure Based Design and in Vivo Reduction of Amyloid β-Peptides. Bioorganic & Medicinal Chemistry Letters, 23. pp. 5300-5306.

Abstract

Previous structure based optimization in our laboratory led to the identification of a novel, high-affinity cyclic sulfone hydroxyethylamine-derived inhibitor such as 1 that lowers CNS-derived Aβ following oral administration to transgenic APP51/16 mice. Herein we report SAR development in the S3 and S2’ subsites of BACE1 for cyclic sulfoxide hydroxyethyl¬amine inhibitors, the synthetic approaches employed in this effort, and in vivo data for optimized compounds such as 11d.

Item Type:	Article
Keywords:	BACE-1 Inhibitor Alzheimer’s disease Structure based design Cyclic sulfoxide hydroxyethylamine inhibitors In vivo reduction of Amyloid β-Peptides
Date Deposited:	18 May 2016 23:45
Last Modified:	18 May 2016 23:45
URI:	https://oak.novartis.com/id/eprint/10008