GPR119 is a G protein-coupled receptor expressed predominantly in pancreatic b-cells and in enteroendocrine cells in the gastrointestinal tract.  GPR119 agonists have been shown to stimulate glucose-dependent insulin release by direct action in the pancreas and to promote secretion of the incretin GLP-1 by action in the GI tract.  This dual mechanism of action has generated significant interest in the discovery of small molecule GPR119 agonists as a potential new treatment for type 2 diabetes.  We have identified a new series of GPR119 agonists based on a pyridone core that has entered human clinical trials. We, herein, describe the discovery, structure-activity relationships (SAR) and preclinical in vivo efficacy studies. We will also provide preliminary data from the single ascending dose clinical trial.

Discovery of BMS-903452, an anti-diabetic clinical candidate targeting GPR119

247th National Meeting (2014)

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