Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Med Chem. 2008 Oct 23;51(20):6259-62. doi: 10.1021/jm800914n. Epub 2008 Sep 24.

Discovery and X-ray crystallographic analysis of a spiropiperidine iminohydantoin inhibitor of beta-secretase.

Author information

  • 1Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. james_barrow@merck.com

Abstract

A high-throughput screen at 100 microM inhibitor concentration for the BACE-1 enzyme revealed a novel spiropiperidine iminohydantoin aspartyl protease inhibitor template. An X-ray cocrystal structure with BACE-1 revealed a novel mode of binding whereby the inhibitor interacts with the catalytic aspartates via bridging water molecules. Using the crystal structure as a guide, potent compounds with good brain penetration were designed.

PMID:
18811140
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society
    Loading ...
    Write to the Help Desk