Author/Authors :
Linda L. Chang، نويسنده , , Kelly L. Sidler، نويسنده , , Margaret A. Cascieri، نويسنده , , Stephen de Laszlo، نويسنده , , Greg Koch، نويسنده , , Bing Li، نويسنده , , Malcolm MacCoss، نويسنده , , Nathan Mantlo، نويسنده , , Stephen OʹKeefe، نويسنده , , Margaret Pang، نويسنده , , Anna Rolando، نويسنده , , William K. Hagmann، نويسنده ,
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, IC50=0.053 μM) and selectivity (>1000×) over p38 MAP kinase in this class of compounds.
