Design and synthesis of potent thiol-based inhibitors of endothelin converting enzyme-1

Authors
Fink, CA Moskal, M Firooznia, F Hoyer, D Symonsbergen, D Wei, DC Qiao, Y Savage, P Beil, ME Trapani, AJ Jeng, AY
Citation
Ca. Fink et al., Design and synthesis of potent thiol-based inhibitors of endothelin converting enzyme-1, BIOORG MED, 10(17), 2000, pp. 2037-2039
Citations number
10
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
10
Issue
17
Year of publication
2000
Pages
2037 - 2039
Database
ISI
SICI code
0960-894X(20000904)10:17<2037:DASOPT>2.0.ZU;2-G
Abstract
Through directed screening of compounds prepared as metalloprotease inhibit ors a compound, CGS 30084, that had potent endothelin converting enzyme-1 ( ECE-1) in vitro inhibitory activity (IC50 = 77 nM) was identified. Herein w e report the synthesis and optimization of ECE-1 inhibitory activity of add itional analogues from this lead. Compound 3c, the thioacetate methyl ester derivative of compound 4c, was found to be a long acting inhibitor of ECE- 1 activity in rats after oral administration. (C) 2000 Elsevier Science Ltd . All rights reserved.