Integration of optimized substituent patterns to produce highly potent 4-aryl-pyridine glucagon receptor antagonists

…, JN Livingston, ML MacDougall, MH Osterhout…

Index: 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. Bioorganic and Medicinal Chemistry Letters, 2002 , vol. 12, # 23 p. 3421 - 3424

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Citation Number: 14

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 ...