Development of 2-aminooxazoline 3-azaxanthene β-amyloid cleaving enzyme (BACE) inhibitors with improved selectivity against Cathepsin D-Reference-Cited by-同舟云学术

Development of 2-aminooxazoline 3-azaxanthene β-amyloid cleaving enzyme (BACE) inhibitors with improved selectivity against Cathepsin D

Published:2017 Issue:6 Volume:8 Page:1196-1206
ISSN:2040-2503
Container-title:MedChemComm
language:en
Short-container-title:Med. Chem. Commun.

Author:

Low Jonathan D.¹²³⁴,Bartberger Michael D.⁵²³⁴,Chen Kui⁶²³⁴,Cheng Yuan¹²³⁴,Fielden Mark R.⁷²³⁴,Gore Vijay¹²³⁴,Hickman Dean⁸²³⁴,Liu Qingyian¹²³⁴,Allen Sickmier E.⁵²⁹⁴,Vargas Hugo M.⁷²³⁴,Werner Jonathan⁷²³⁴,White Ryan D.¹²⁹⁴,Whittington Douglas A.⁵²⁹⁴,Wood Stephen¹⁰²³⁴,Minatti Ana E.¹²³⁴^ORCID

Affiliation:

1. Department of Medicinal Chemistry

2. Amgen Inc.

3. Thousand Oaks

4. USA

5. Department of Molecular Engineering

6. Department Discovery Technologies

7. Comparative Biology and Safety Sciences

8. Department of Pharmacokinetics and Drug Metabolism

9. Cambridge

10. Department of Neuroscience

Abstract

We report the discovery of an orally efficacious 3-aza-aminooxazoline-BACE1 inhibitor with 1 800 000× fold selectivity against CatD and no retinal effects in an early screening rat toxicology study.

Publisher

Royal Society of Chemistry (RSC)

Subject

Pharmaceutical Science,Biochemistry,Drug Discovery,Molecular Medicine,Pharmacology,Organic Chemistry

Link

http://pubs.rsc.org/en/content/articlepdf/2017/MD/C7MD00106A

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