Author/Authors :
Roger A. Smith، نويسنده , , Donald L. Hertzog، نويسنده , , Martin H. Osterhout، نويسنده , , Gaetan H. Ladouceur، نويسنده , , Mary Korpusik، نويسنده , , Mark A. Bobko، نويسنده , , J. Howard Jones، نويسنده , , Kathleen Phelan، نويسنده , , Romulo H. Romero، نويسنده , , Thomas Hundertmark، نويسنده , , Margit L. MacDougall، نويسنده , , James N. Livingston، نويسنده , , William R. Schoen، نويسنده ,
Abstract :
A narrow structure–activity relationship was established for the 4-aryl group in 4-aryl-pyridine glucagon antagonists, with only small substituents being well-tolerated, and only at the 3′- and 4′-positions. However, substitution with a 2′-hydroxy group gave a ca. 3-fold increase in activity (e.g., 4′-fluoro-2′-hydroxy analogue 33, IC50=190 nM). For efficient preparation of 2′-substituted phenylpyridines, a novel synthesis via pyrones and 4-methoxy-pyridines was developed.
