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

US8173810B2 · 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
• Daniel B. Horne · Natick, US
• Matthew Kaller · Ventura, US
• Charles Kreiman · Watertown, US
• Patricia Lopez · Calabasas, US
• Holger Monenschein · San Diego, US
• Thomas Nguyen · Newbury Park, US
• Lewis D. Pennington · Ventura, US
• Qiufen Xue · Thousand Oaks, US
• Bryant Yang · Simi Valley, US
• Yuan Cheng · Newbury Park, US

Key dates

• Filing date: May 23, 2008
• Grant date: May 8, 2012
• Expiry date: Feb 26, 2031

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 enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula Iwherein R1a, R1b, R1c, B, W, R3, R4 and R5 are defined herein. In another embodiment, the invention provides compounds of general Formula IIwherein A1, A2, A3, A4, R1a, R1b, R1c, R2, R4, R5, W, X and Z are defined herein.The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease (AD), cognitive deficits and impairment, schizophrenia and other similar central nervous system conditions. The invention also comprises further embodiments of Formula II, intermediates and processes useful for the preparation of compounds of Formulas I and II.