Discovery of 5-hydroxyalkyl-4-phenylpyridines as a new class of glucagon receptor antagonists

Bioorg Med Chem Lett. 2002 Feb 11;12(3):461-4. doi: 10.1016/s0960-894x(01)00766-1.

Abstract

5-Hydroxyalkyl-4-phenylpyridines have been identified as a novel class of glucagon antagonists with potential utility for the treatment of diabetes. A lead structure with moderate activity was discovered through a high throughput screening assay. Structure-activity relationships led to the discovery of a potent antagonist, IC(50)=0.11 microM, more than 60-fold improvement over the lead structure.

MeSH terms

  • Crystallography, X-Ray
  • Drug Design
  • Drug Evaluation, Preclinical
  • Humans
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / pharmacology*
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology*
  • Receptors, Glucagon / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Hypoglycemic Agents
  • Pyridines
  • Receptors, Glucagon