Substituted imidazoles as glucagon receptor antagonists

Bioorg Med Chem Lett. 2001 Sep 17;11(18):2549-53. doi: 10.1016/s0960-894x(01)00498-x.

Abstract

A modestly active, nonselective triarylimidazole lead was optimized for binding affinity with the human glucagon receptor. This led to the identification of a 2- and/or 4-alkyl or alkyloxy substituent on the imidazole C4-aryl group as a structural determinant for significant enhancement in binding with the glucagon receptor (e.g., 41, IC(50)=0.053 microM) and selectivity (>1000x) over p38MAP kinase in this class of compounds.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Drug Design
  • Drug Evaluation, Preclinical
  • Humans
  • Imidazoles / chemistry
  • Inhibitory Concentration 50
  • Magnesium / metabolism
  • Magnesium / pharmacology
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • Pyridines / chemistry*
  • Pyridines / metabolism
  • Pyridines / pharmacology*
  • Receptors, Glucagon / antagonists & inhibitors*
  • Receptors, Glucagon / metabolism
  • Structure-Activity Relationship
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Imidazoles
  • Pyridines
  • Receptors, Glucagon
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Magnesium