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Substituted imidazoles as glucagon receptor antagonists

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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 11, 期 18, 页码 2549-2553

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0960-894X(01)00498-X

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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.

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