Optimization of the 4-aryl group of 4-aryl-pyridine glucagon antagonists: development of an efficient, alternative synthesis

…, T Hundertmark, ML MacDougall, JN Livingston…

Index: 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. Bioorganic and Medicinal Chemistry Letters, 2002 , vol. 12, # 9 p. 1303 - 1306 Title/Abstract Full Text View citing articles Show Details 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: 13

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 (eg, 4′-fluoro-2′-hydroxy analogue 33, IC50= 190 nM). For efficient preparation of 2′-substituted phenylpyridines, a novel synthesis via pyrones and 4- ...