Synthesis and structure activity relationships of novel small molecule cathepsin D inhibitors

Authors
Dumas, J Brittelli, D Chen, JS Dixon, B Hatoum-Mokdad, H Konig, G Sibley, R Witowsky, J Wong, S
Citation
J. Dumas et al., Synthesis and structure activity relationships of novel small molecule cathepsin D inhibitors, BIOORG MED, 9(17), 1999, pp. 2531-2536
Citations number
15
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
9
Issue
17
Year of publication
1999
Pages
2531 - 2536
Database
ISI
SICI code
0960-894X(19990906)9:17<2531:SASARO>2.0.ZU;2-E
Abstract
Cathepsin D, a lysosomal aspartyl protease, has been implicated in the path ology of Alzheimer's disease as well as breast and ovarian cancer. A weakly active cathepsin D inhibitor was identified by high throughput screening. Subsequent optimization led to the discovery of a new class of small molecu le inhibitors of this enzyme, culminating with the sulfonamide 13 (IC50 = 2 50 nM), (C) 1999 Elsevier Science Ltd. All rights reserved.