Substituted Imidazoles as Glucagon Receptor Antagonists
摘要:
A modestly active, nonselective triarylimidazole lead was optimized for binding affinity with the human glucagon receptor. This led to the identification 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 with the glucagon receptor (e.g., 41, IC50 = 0.053 muM) and selectivity (> 1000x) over p38 MAP kinase in this class of compounds. (C) 2001 Elsevier Science Ltd. All rights reserved.
Substituted Imidazoles as Glucagon Receptor Antagonists
作者:Linda L. Chang、Kelly L. Sidler、Margaret A. Cascieri、Stephen de Laszlo、Greg Koch、Bing Li、Malcolm MacCoss、Nathan Mantlo、Stephen O'Keefe、Margaret Pang、Anna Rolando、William K. Hagmann
DOI:10.1016/s0960-894x(01)00498-x
日期:2001.9
A modestly active, nonselective triarylimidazole lead was optimized for binding affinity with the human glucagon receptor. This led to the identification 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 with the glucagon receptor (e.g., 41, IC50 = 0.053 muM) and selectivity (> 1000x) over p38 MAP kinase in this class of compounds. (C) 2001 Elsevier Science Ltd. All rights reserved.