Cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use
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.
Amgen, Inc.
C A A A A C C C C C A
C07D A61P A61P A61P A61P C07D C07D C07D C07D C07D A61P
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Ana Elena Paul E. Jian J. Qiufen James Angel Vu Van Albert Longbin Markian M. Alexander J. Thomas T. Qingyian Yuan Jennifer R. Matthew P. Mark H. Shannon Ryan D. James A. Michael J. Wenyuan Nobuko Liping H. Jonathan D. Aaron C. Robert M.
Minatti Harrington Chen Xue Manning Guzman-Perez Ma Amegadzie Liu Stec Pickrell Nguyen Liu Cheng Allen Bourbeau Norman Rumfelt White Brown Frohn Qian Nishimura Pettus Low Siegmund Rzasa