Perfluorinated cyclopropyl fused 1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use

US9611261B2 · kind B2 · utility

Assignee

• AMGEN INC. · US

Inventors

• Ana Elena Minatti · Santa Monica, US
• Jonathan D. Low · Thousand Oaks, US
• Jennifer R. Allen · Newbury Park, US
• Albert Amegadzie · Moorpark, US
• James Brown · Moorpark, US
• Michael J. Frohn · Thousand Oaks, US
• Angel Guzman-Perez · Belmont, US
• Paul E. Harrington · Camarillo, US
• Patricia Lopez · Calabasas, US
• Vu Van Ma · Simi Valley, US
• Nobuko Nishimura · Calabasas, US
• Wenyuan Qian · Newbury Park, US
• Shannon Rumfelt · Camarillo, US
• Robert M. Rzasa · Ventura, US
• Kelvin Sham · Thousand Oaks, US
• Adrian L. Smith · Simi Valley, US
• Ryan White · Thousand Oaks, US
• Qiufen Xue · Thousand Oaks, US

Key dates

• Filing date: Nov 4, 2015
• Grant date: Apr 4, 2017
• Expiry date: Nov 4, 2035

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D491/048
• 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, each of Ra, Rb, R1, R2, R3 and R7 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and 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 Formulas II and III, and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.