Substituted hydroxyethyl amine compounds as beta-secretase modulators and methods of use

US8552181B2 · kind B2 · utility

Assignee

• AMGEN INC. · US

Inventors

• Wenge Zhong · Thousand Oaks, US
• Stephen Hitchcock · San Diego, US
• Vinod F. Patel · Acton, US
• Michael Croghan · Thousand Oaks, US
• Thomas A. Dineen · Somerville, US
• Scott Harried · Calabasas, US
• Daniel B. Horne · Natick, US
• Ted Judd · San Fernando, US
• Matthew Walker · London, GB
• Charles Kreiman · Watertown, US
• Patricia Lopez · Calabasas, US
• Holger Monenschein · San Diego, US
• Thomas Nguyen · Newbury Park, US
• Matthew Weiss · Boston, US
• Qiufen Xue · Thousand Oaks, US
• Bryant Yang · Simi Valley, US
• Russell Graceffa · Hampton, US

Key dates

• Filing date: Mar 1, 2012
• Grant date: Oct 8, 2013
• Expiry date: Mar 1, 2032

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D495/10
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present invention comprises a new class of compounds useful for the modulation of Beta-secretase activity and for the treatment of diseases, including Alzheimer's disease (AD) and related CNS conditions, mediated thereby. In one embodiment, the compounds have a general Formula Ior Formula IIwherein R1a-1c, B, R3-5 and W of Formula I, and R1a-1c, R2-5, A1-4, W, X, Z, m and n of Formula II are defined herein. The invention further provides compounds of Formula III and IV and sub-Formulas II-A-II-D and III-A-III-D. The compounds may be used in pharmaceutical compositions for treating, prophylactically or therapeutically, disorders related to the activity of beta-secretase protein, including without limitation, AD, cognitive deficits and impairment, schizophrenia and other similar central nervous system conditions.