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

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 (IC 50  = 34 nM) and moderate bioavailability (36% in mice).