Discovery of 5-Hydroxyalkyl-4-phenylpyridines as a New Class of Glucagon Receptor Antagonists.

Abstract 5-Hydroxyalkyl-4-phenylpyridines have been identified as a novel class of glucagon antagonists with potential utility for the treatment of diabetes. A lead structure with moderate activity was discovered through a high throughput screening assay. Structure–activity relationships led to the discovery of a potent antagonist, IC 50 =0.11 μM, more than 60-fold improvement over the lead structure.