Discovery of Glucagon-like Peptide 1 Receptor (GLP-1R) small molecule agonist

Abstract

Glucagon-like peptide 1, an incretin hormone that induces insulin secretion, suppresses of glucagon secretion maintains beta cell function and reduces beta cell apoptosis, has emerged as a target for T2DM. To date, various GLP-1 agonists were reported, most of them are peptide, which has a limitation for oral treatment. For overcoming the problems, studies have been focused on developing small molecules, GLP-1 positive allosteric modulators (PAMs) and direct agonists. In this thesis, we selected B2783 which is a hit from HTS and synthesized some derivatives. Among them, compound 9d showed a good activity as a GLP-1 agonist.