Author/Authors :
Gaetan H. Ladouceur، نويسنده , , James H. Cook، نويسنده , , Donald L. Hertzog، نويسنده , , J. Howard Jones، نويسنده , , Thomas Hundertmark، نويسنده , , Mary Korpusik، نويسنده , , Timothy G. Lease، نويسنده , , James N. Livingston، نويسنده , , Margit L. MacDougall، نويسنده , , Martin H. Osterhout، نويسنده , , Kathleen Phelan، نويسنده , , Romulo H. Romero، نويسنده , , William R. Schoen، نويسنده , , Chunning Shao، نويسنده , , Roger A. Smith، نويسنده ,
Abstract :
Optimized substituent patterns in 4-aryl-pyridine glucagon receptor antagonists were merged to produce highly potent derivatives containing both a 3-[(1R)-hydroxyethyl] and a 2′-hydroxy group. Due to restricted rotation of the phenyl–pyridine bond, these analogues exist as four isomers. A diastereoselective methylcopper reaction was developed to facilitate the synthesis, and single isomers were isolated with activities in the range IC50=10–25 nM.
