470717-47-6Relevant articles and documents
Optimization of the 4-aryl group of 4-aryl-pyridine glucagon antagonists: Development of an efficient, alternative synthesis
Smith, Roger A.,Hertzog, Donald L.,Osterhout, Martin H.,Ladouceur, Gaetan H.,Korpusik, Mary,Bobko, Mark A.,Jones,Phelan, Kathleen,Romero, Romulo H.,Hundertmark, Thomas,MacDougall, Margit L.,Livingston, James N.,Schoen, William R.
, p. 1303 - 1306 (2002)
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.
Integration of optimized substituent patterns to produce highly potent 4-aryl-pyridine glucagon receptor antagonists
Ladouceur, Gaetan H.,Cook, James H.,Hertzog, Donald L.,Jones,Hundertmark, Thomas,Korpusik, Mary,Lease, Timothy G.,Livingston, James N.,MacDougall, Margit L.,Osterhout, Martin H.,Phelan, Kathleen,Romero, Romulo H.,Schoen, William R.,Shao, Chunning,Smith, Roger A.
, p. 3421 - 3424 (2007/10/03)
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.
