Substituted imidazoles as glucagon receptor antagonists

Authors
Chang, LL Sidler, KL Cascieri, MA de Laszlo, S Koch, G Li, B MacCoss, M Mantlo, N O'Keefe, S Pang, M Rolando, A Hagmann, WK
Citation
Ll. Chang et al., Substituted imidazoles as glucagon receptor antagonists, BIOORG MED, 11(18), 2001, pp. 2549-2553
Citations number
24
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
18
Year of publication
2001
Pages
2549 - 2553
Database
ISI
SICI code
0960-894X(20010917)11:18<2549:SIAGRA>2.0.ZU;2-A
Abstract
A modestly active, nonselective triarylimidazole lead was optimized for bin ding affinity with the human glucagon receptor. This led to the identificat ion of a 2- and/or 4-alkyl or alkyloxy substituent on the imidazole C4-aryl group as a structural determinant for significant enhancement in binding w ith the glucagon receptor (e.g., 41, IC50 = 0.053 muM) and selectivity (> 1 000x) over p38 MAP kinase in this class of compounds. (C) 2001 Elsevier Sci ence Ltd. All rights reserved.