Discovery and investigation of a novel class of thiophene-derived antagonists of the human glucagon receptor

Bioorg Med Chem Lett. 2005 Mar 1;15(5):1401-5. doi: 10.1016/j.bmcl.2005.01.003.

Abstract

A novel class of antagonists of the human glucagon receptor (hGCGR) has been discovered. Systematic modification of the lead compound identified substituents that were essential for activity and those that were amenable to further optimization. This SAR exploration resulted in the synthesis of 13, which exhibited good potency as an hGCGR functional antagonist (IC50 = 34 nM) and moderate bioavailability (36% in mice).

MeSH terms

  • Humans
  • Molecular Structure
  • Receptors, Glucagon / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis*
  • Thiophenes / classification
  • Thiophenes / pharmacology*

Substances

  • Receptors, Glucagon
  • Thiophenes