Synthesis and biological activity of novel potent endothelin-converting enzyme-1 inhibitors

Authors
Firooznia, F Gude, C Chan, K Fink, CA Qiao, Y Satoh, Y Marcopoulos, N Savage, P Beil, ME Bruseo, CW Trapani, AJ Jeng, AY
Citation
F. Firooznia et al., Synthesis and biological activity of novel potent endothelin-converting enzyme-1 inhibitors, BIOORG MED, 11(3), 2001, pp. 375-378
Citations number
20
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
3
Year of publication
2001
Pages
375 - 378
Database
ISI
SICI code
0960-894X(20010212)11:3<375:SABAON>2.0.ZU;2-4
Abstract
Through directed screening of metalloprotease inhibitors. CGS 30084 (1) has been identified as a potent endothelin-converting enzyme-1 (ECE-1) inhibit or in vitro (IC50 = 77 nM). Herein we report the synthesis and biological a ctivities of analogues derived from this lead. based on modifications of th e biphenyl moiety. Compound 10. the thioacetate methyl ester prodrug deriva tive of compound 6m. was found to he an orally active and potent inhibitor of ECE-1 activity in rats. (C) 2001 Elsevier science Ltd. All rights reserv ed.