Substituted imidazoles as glucagon receptor antagonists. |
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| Authors: | L L Chang K L Sidler M A Cascieri S de Laszlo G Koch B Li M MacCoss N Mantlo S O'Keefe M Pang A Rolando W K Hagmann |
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| Affiliation: | Department of Medicinal Chemical Research, Merck Research Laboratories, Rahway, NJ 07065, USA. linda_chang@merck.com |
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| 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 (e.g., 41, IC(50)=0.053 microM) and selectivity (>1000x) over p38MAP kinase in this class of compounds. |
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