Substituted imidazoles as glucagon receptor antagonists

…, G Koch, B Li, M MacCoss, N Mantlo, S O'Keefe…

Index: Chang, Linda L.; Sidler, Kelly L.; Cascieri, Margaret A.; De Laszlo, Stephen; Koch, Greg; Li, Bing; MacCoss, Malcolm; Mantlo, Nathan; O'Keefe, Stephen; Pang, Margaret; Rolando, Anna; Hagmann, William K. Bioorganic and Medicinal Chemistry Letters, 2001 , vol. 11, # 18 p. 2549 - 2553

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Citation Number: 104

Abstract

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 (eg, 41, IC50= 0.053 μM) and selectivity (> 1000×) over p38MAP kinase in this class of compounds.