Potent, orally absorbed glucagon receptor antagonists

Bioorg Med Chem Lett. 1999 Mar 8;9(5):641-6. doi: 10.1016/s0960-894x(99)00081-5.

Abstract

The SAR of 2-pyridyl-3,5-diaryl pyrroles, ligands of the human glucagon receptor and inhibitors of p38 kinase, were investigated. This effort resulted in the identification of 2-(4-pyridyl)-5-(4-chlorophenyl)-3-(5-bromo-2-propyloxyphenyl)pyrr ole 49 (L-168,049), a potent (Kb = 25 nM), selective antagonist of glucagon.

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Mice
  • Mitogen-Activated Protein Kinases*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Receptors, Glucagon / antagonists & inhibitors*
  • Structure-Activity Relationship
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Enzyme Inhibitors
  • L 168049
  • Pyridines
  • Pyrroles
  • Receptors, Glucagon
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases