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Updated: May 28, 2026

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
Published on: May 10, 2018
Discovery of cyclic guanidines as potent, orally active, human glucagon receptor antagonists
Christopher Sinz1, Jiang Chang, Ashley Rouse Lins
1Discovery and Preclinical Sciences, Merck Research Laboratories, Rahway, NJ 07065, USA. christopher_sinz@merck.com
Abstract:
In the course of the development of an aminobenzimidazole class of human glucagon receptor (hGCGR) antagonists, a novel class of cyclic guanidine hGCGR antagonists was discovered. Rapid N-dealkylation resulted in poor pharmacokinetic profiles for the benchmark compound in this series. A strategy aimed at blocking oxidative dealkylation led to a series of compounds with improved rodent pharmacokinetic profiles. One compound was orally efficacious in a murine glucagon challenge pharmacodynamic model and also significantly lowered glucose levels in a murine diabetes model.
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