Amino-dihydrothiazine and amino-dioxido dihydrothiazine compounds as beta-secretase antagonists and methods of use

US9556135B2 · kind B2 · utility

Assignee

• AMGEN INC. · US

Inventors

• Richard T. Lewis · Missouri City, US
• Jennifer R. Allen · Newbury Park, US
• Yuan Cheng · Newbury Park, US
• Deborah Choquette · Medford, US
• Oleg Epstein · Belmont, US
• Angel Guzman-Perez · Belmont, US
• Paul E. Harrington · Camarillo, US
• Zihao Hua · Andover, US
• Randall W. Hungate · Lansdale, US
• Jason Brooks Human · Boston, US
• Ted Judd · San Fernando, US
• Qingyian Liu · Camarillo, US
• Patricia Lopez · Calabasas, US
• Ana Elena Minatti · Santa Monica, US
• Philip R. Olivieri · Boston, US
• Karina Romero · Cambridge, US
• Shannon Rumfelt · Camarillo, US
• Robert M. Rzasa · Ventura, US
• Laurie B. Schenkel · Somerville, US
• John Stellwagen · Newbury Park, US
• Ryan White · Thousand Oaks, US
• Qiufen Xue · Thousand Oaks, US
• Xiao Mei Zheng · Natick, US
• Wenge Zhong · Thousand Oaks, US

Key dates

• Filing date: Oct 10, 2013
• Grant date: Jan 31, 2017
• Expiry date: Oct 10, 2033

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D519/00
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A4, A5, A6, A8, R1, R2, R3, R7 and n of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formula II and sub-formula embodiments thereof, intermediates and processes and methods useful for the preparation of compounds of Formulas I-II.