Design and synthesis of irreversible depsipeptidyl human rhinovirus 3C protease inhibitors

Authors
Webber, SE Marakovits, JT Dragovich, PS Prins, TJ Zhou, R Fuhrman, SA Patick, AK Matthews, DA Lee, CA Srinivasan, B Moran, T Ford, CE Brothers, MA Harr, JEV Meador, JW Ferre, RA Worland, ST
Citation
Se. Webber et al., Design and synthesis of irreversible depsipeptidyl human rhinovirus 3C protease inhibitors, BIOORG MED, 11(20), 2001, pp. 2683-2686
Citations number
18
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
20
Year of publication
2001
Pages
2683 - 2686
Database
ISI
SICI code
0960-894X(20011022)11:20<2683:DASOID>2.0.ZU;2-Q
Abstract
Novel tripeptidyl C-terminal Michael acceptors with an ester replacement of the P-2-P-3 amide bond were investigated as irreversible inhibitors of the human rhinovirus (HRV) 3C protease (3CP). When screened against HRV seroty pe-14 the best compound was shown to have very good 3CP inhibition (k(obs)/ [I]=270,000 M(-1)s(-1)) and potent in vitro antiviral activity (EC50 = 7.0 nM). (C) 2001 Elsevier Science Ltd. All rights reserved.