Structure-based design of irreversible, tripeptidyl human rhinovirus 3C protease inhibitors containing N-methyl amino acids

Authors
Dragovich, PS Webber, SE Prins, TJ Zhou, R Marakovits, JT Tikhe, JG Fuhrman, SA Patick, AK Matthews, DA Ford, CE Brown, EL Binford, SL Meador, JW Ferre, RA Worland, ST
Citation
Ps. Dragovich et al., Structure-based design of irreversible, tripeptidyl human rhinovirus 3C protease inhibitors containing N-methyl amino acids, BIOORG MED, 9(15), 1999, pp. 2189-2194
Citations number
31
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
9
Issue
15
Year of publication
1999
Pages
2189 - 2194
Database
ISI
SICI code
0960-894X(19990802)9:15<2189:SDOITH>2.0.ZU;2-X
Abstract
Tripeptide-derived molecules incorporating N-methyl amino acid residues and C-terminal Michael acceptor moieties were evaluated as irreversible inhibi tors of the cysteine-containing human rhinovirus 3C protease (3CP). Such co mpounds displayed good 3CP inhibition activity (k(obs)/[I] up to 610,000 M( -1)s(-1)) and potent in vitro antiviral properties (EC50 approaching 0.03 m u M) when tested against HRV serotype-14. (C) 1999 Elsevier Science Ltd. Al l rights reserved.