Vinyl fluoride cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use

US10246429B2 · 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
• Ning Chen · Thousand Oaks, US
• Michael J. Frohn · Thousand Oaks, US
• Longbin Liu · Thousand Oaks, US
• Qingyian Liu · Camarillo, US
• Liping H. Pettus · Thousand Oaks, US
• Wenyuan Qian · Newbury Park, US
• Corey REEVES · West Hollywood, US
• Aaron C. Siegmund · Ventura, US

Key dates

• Filing date: Aug 4, 2016
• Grant date: Apr 2, 2019
• Expiry date: Aug 4, 2036

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07F7/0812
• 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, A7, and each of Ra, Rb, R1, R2, R3, R8 R9 and R10 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 Aβ 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.