Spiro-tetracyclic ring compounds as beta-secretase modulators and methods of use

US8883782B2 · kind B2 · utility

Assignee

• AMGEN INC. · US

Inventors

• Yuan Cheng · Newbury Park, US
• Ryan White · Thousand Oaks, US
• Albert Amegadzie · Moorpark, US
• James Brown · Moorpark, US
• Alan C. Cheng · Cambridge, US
• Erin F. Dimauro · Cambridge, US
• Thomas A. Dineen · Somerville, US
• Oleg Epstein · Belmont, US
• Vijay Keshav Gore · Thousand Oaks, US
• Jason Brooks Human · Boston, US
• Ted Judd · San Fernando, US
• Charles Kreiman · Watertown, US
• Qingyian Liu · Camarillo, US
• Patricia Lopez · Calabasas, US
• Vu Van Ma · Simi Valley, US
• Isaac Marx · Somerville, US
• Ana Elena Minatti · Santa Monica, US
• Hanh Nho Nguyen · North Palm Beach, US
• Nick A. Paras · Santa Monica, US
• Vinod F. Patel · Acton, US
• Wenyuan Qian · Newbury Park, US
• Matthew Weiss · Boston, US
• Qiufen Xue · Thousand Oaks, US
• Xiao Mei Zheng · Natick, US
• Wenge Zhong · Thousand Oaks, US

Key dates

• Filing date: Mar 14, 2011
• Grant date: Nov 11, 2014
• Expiry date: Apr 22, 2033

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K31/5377
• WIPO field: Pharmaceuticals
• 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 other related conditions. In one embodiment, the compounds have a general Formula Iwherein A1, A2, A3, A4, A5, A6, R2, R7, X and Y of Formula I 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, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.