Bioorganic & Medicinal Chemistry Letters 28 (2018) 1111–1115 Contents lists available at ScienceDirect Bioorganic & Medicinal Chemistry Letters journal homepage: www.elsevier.com/locate/bmcl Diastereoselective synthesis of fused cyclopropyl-3-amino-2,4-oxazine b-amyloid cleaving enzyme (BACE) inhibitors and their biological evaluation a,⇑ b a c,e a Jonathan D. Low , Michael D. Bartberger , Yuan Cheng , Doug Whittington , Quifen Xue , d a a,⇑ Stephen Wood , Jennifer R. Allen , Ana E. Minatti Department of Medicinal Chemistry, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA Department of Molecular Engineering, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA Department of Molecular Engineering, Amgen Inc., 360 Binney Street, Cambridge, MA 02142, USA Department of Neuroscience, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA article i nfo abstract Article history: The diastereoselective synthesis and structure activity relationship (SAR) of a series of fused cyclopropyl- Received 3 January 2018 3-amino-2,4-oxazine (2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine)-containing BACE inhibitors is Revised 24 January 2018 described. Through these efforts compound 2 was identiﬁed as a potent (cell IC = 15 nM) BACE inhibitor Accepted 26 January 2018 with acceptable ADME properties. When tested in vivo, compound 2 demonstrated a signiﬁcant reduc- Available online 1
Bioorganic & Medicinal Chemistry Letters – Elsevier
Published: Apr 1, 2018
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