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

  • Bioorg Med Chem Lett. 2002 Dec 2;12(23):3421-4. doi: 10.1016/s0960-894x(02)00736-9.
Gaetan H Ladouceur  1 ,  James H Cook ,  Donald L Hertzog ,  J Howard Jones ,  Thomas Hundertmark ,  Mary Korpusik ,  Timothy G Lease ,  James N Livingston ,  Margit L MacDougall ,  Martin H Osterhout ,  Kathleen Phelan ,  Romulo H Romero ,  William R Schoen ,  Chunning Shao ,  Roger A Smith
Affiliations
  • 1. Department of Chemistry Research, Bayer Research Center, West Haven, CT 06516, USA. [email protected]
PMID: 12419375 DOI: 10.1016/s0960-894x(02)00736-9
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 IC(50)=10-25 nM.

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