Discovery of thiophene-containing biaryl amide derivatives as novel glucagon receptor antagonists

Chem Biol Drug Des. 2018 Jul;92(1):1241-1254. doi: 10.1111/cbdd.13184. Epub 2018 Apr 10.

Abstract

A novel series of thiophene-containing biaryl amide glucagon receptor (GCGR) antagonists were designed and synthesized. Two compounds of this series, 14f and 14h, exhibited good GCGR binding (IC50 = 6.1 and 4.4 μm, respectively) and cAMP functional activities (IC50 = 4.4 and 14.4 μm, respectively). The possible binding modes of compounds 14f and 14h with GCGR were explored by molecular simulation.

Keywords: biaryl amide; glucagon receptor antagonist; molecular simulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Amides / metabolism
  • Binding Sites
  • Cyclic AMP / metabolism
  • Hydrophobic and Hydrophilic Interactions
  • Molecular Docking Simulation
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Glucagon / antagonists & inhibitors*
  • Receptors, Glucagon / metabolism
  • Structure-Activity Relationship
  • Thiophenes / chemistry*

Substances

  • Amides
  • Receptors, Glucagon
  • Thiophenes
  • Cyclic AMP