Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 23, Issue 1, Pages 85-89Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2012.11.011
Keywords
BACE-1; Benzodiazepines; Alzheimer's disease; Memapsin 2; beta-Secretase
Categories
Funding
- European Research Centre for Drug Discovery and Development (NatSynDrugs)
- MIUR Prin
- Regione Campania L.R. [05/02]
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Aiming at identifying new scaffolds for BACE-1 inhibition devoid of the pharmacokinetic drawbacks of peptide-like structures, we investigated a series of novel peptidomimetics based on a 1,4-benzodiazepine (BDZ) core 1a-h and their seco-analogues 2a-d. We herein discuss synthesis, molecular modeling and in vitro studies which, starting from 1a, led to the seco-analogues (R)-2c and (S)-2d endowed with BACE-1 inhibition properties in the micromolar range both on the isolated enzyme and in cellular studies. These data can encourage to pursue these analogues as hits for the development of a new series of BACE-1 inhibitors active on whole-cells. (C) 2012 Elsevier Ltd. All rights reserved.
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