Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

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Inhibition of BACE-1 by Hydroxyethylsulfide, Hydroxyethylamine and Hydroxyethylurea Isosteric Replacements

Author(s): L. Rizzi, S. Romeo.

Abstract:

New inhibitors of the ß-site amyloid precursor protein cleaving enzyme (BACE-1) are described. The hydroxyethyl transition state isostere of GT1017 has been replaced by the hydroxyethylamine (HEA), the hydroxyethylsulfide or the hydroxyethylurea groups. Biological evaluation has shown that the HEA analogue, obtained as epimeric mixture, inhibited BACE-1 with an IC50=0.12μM. Stereoselective synthesis showed surprisingly that the most active stereoisomer was the (R)-HEA transition state analogue with an IC50=0.014μM.

Keywords: bace-1, secretase, memapsin-2, inhibition, transition state analogues, pseudopeptides

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Article Details

VOLUME: 2
ISSUE: 2
Year: 2005
Page: [109 - 112]
Pages: 4
DOI: 10.2174/1570180053175142
Price: $58