Diastereoselective synthesis of fused cyclopropyl-3-amino-2,4-oxazine β-amyloid cleaving enzyme (BACE) inhibitors and their biological evaluation

Diastereoselective synthesis of fused cyclopropyl-3-amino-2,4-oxazine β-amyloid cleaving enzyme... 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 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Bioorganic & Medicinal Chemistry Letters Elsevier

Diastereoselective synthesis of fused cyclopropyl-3-amino-2,4-oxazine β-amyloid cleaving enzyme (BACE) inhibitors and their biological evaluation

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Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier Ltd
ISSN
0960-894x
D.O.I.
10.1016/j.bmcl.2018.01.056
Publisher site
See Article on Publisher Site

Abstract

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

Journal

Bioorganic & Medicinal Chemistry LettersElsevier

Published: Apr 1, 2018

References

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