Discovery of novel non-peptide inhibitors of BACE-1 using virtual high-throughput screening

N Yi Mok; James Chadwick; Katherine A B Kellett; Nigel M Hooper; A Peter Johnson; Colin W G Fishwick

doi:10.1016/j.bmcl.2009.09.103

Discovery of novel non-peptide inhibitors of BACE-1 using virtual high-throughput screening

Bioorg Med Chem Lett. 2009 Dec 1;19(23):6770-4. doi: 10.1016/j.bmcl.2009.09.103. Epub 2009 Oct 2.

Authors

N Yi Mok¹, James Chadwick, Katherine A B Kellett, Nigel M Hooper, A Peter Johnson, Colin W G Fishwick

Affiliation

¹ School of Chemistry, University of Leeds, Leeds LS2 9JT, UK.

PMID: 19854048
DOI: 10.1016/j.bmcl.2009.09.103

Abstract

A novel series of isatin-based inhibitors of beta-secretase (BACE-1) have been identified using a virtual high-throughput screening approach. Structure-activity relationship studies revealed structural features important for inhibition. Docking studies suggest these inhibitors may bind within the BACE-1 active site through H-bonding interactions involving the catalytic aspartate residues.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid Precursor Protein Secretases / antagonists & inhibitors*
Catalytic Domain
Combinatorial Chemistry Techniques / methods*
Computational Biology
Crystallography, X-Ray
Drug Discovery*
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Hydrogen Bonding
Isatin / chemical synthesis
Isatin / chemistry
Isatin / pharmacology*
Models, Molecular
Molecular Structure
Stereoisomerism
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Isatin
Amyloid Precursor Protein Secretases