Gaetan Ladouceur

Discovery of 5-hydroxyalkyl-4-phenylpyridines as a new class of glucagon receptor antagonists.

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 microM, more than 60-fold improvement over the lead structure.

4-Phenylpyridine glucagon receptor antagonists: synthetic approaches to the sterically hindered chiral hydroxy group

Abstract Systematic evaluation of the structure–activity relationships of a new class of 4-aryl-pyridine glucagon antagonists led to the discovery of potent analogues bearing a key secondary hydroxy moiety as seen in compound 1a . Due to the importance of this new class of compounds, it became necessary to establish an efficient synthesis of the pure enantiomer. A resolution and two chiral syntheses of alcohol 1a were discovered and herein presented.