Cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use

US9550762B2 · kind B2 · utility

Assignee

• AMGEN INC. · US

Inventors

• Jennifer R. Allen · Newbury Park, US
• Albert Amegadzie · Moorpark, US
• Matthew P. Bourbeau · Calabasas, US
• James Brown · Moorpark, US
• Jian Chen · Camarillo, US
• Yuan Cheng · Newbury Park, US
• Michael J. Frohn · Thousand Oaks, US
• Angel Guzman-Perez · Belmont, US
• Paul E. Harrington · Camarillo, US
• Longbin Liu · Thousand Oaks, US
• Qingyian Liu · Camarillo, US
• Jonathan D. Low · Thousand Oaks, US
• Vu Van Ma · Simi Valley, US
• James R. MANNING · Pleasant Hill, US
• Ana Elena Minatti · Santa Monica, US
• Thomas Nguyen · Newbury Park, US
• Nobuko Nishimura · Calabasas, US
• Mark H. Norman · Thousand Oaks, US
• Liping H. Pettus · Thousand Oaks, US
• Alexander J. Pickrell · Westlake Village, US
• Wenyuan Qian · Newbury Park, US
• Shannon Rumfelt · Camarillo, US
• Robert M. Rzasa · Ventura, US
• Aaron C. Siegmund · Ventura, US
• Markian Stec · Thousand Oaks, US
• Ryan White · Thousand Oaks, US
• Qiufen Xue · Thousand Oaks, US

Key dates

• Filing date: Aug 5, 2015
• Grant date: Jan 24, 2017
• Expiry date: Aug 5, 2035

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D513/10
• 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, and 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.