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

Loading next page...
 
/lp/elsevier/diastereoselective-synthesis-of-fused-cyclopropyl-3-amino-2-4-oxazine-pmHTlCSXIs
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

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off