Discovery of benzothiazole derivatives as efficacious and enterocyte-specific MTP inhibitors

A series of triamide derivatives bearing a benzothiazole core is shown to be potent microsomal triglyceride transfer protein (MTP) inhibitors. In order to minimize liver toxicity, these compounds have been optimized to have activity only in the enterocytes and have limited systemic bioavailability. Upon oral administration, selected analogs within this series have been further demonstrated to reduce food intake along with body weight and thereby improve glucose homeostasis and insulin sensitivity in a 28-day mice diet-induced obesity (DIO) model.

Graphical abstractA series of benzothiazole derivatives is shown to be potent MTP inhibitors, with some showing oral activity in a mice diet-induced obesity model.Figure optionsDownload full-size imageDownload as PowerPoint slide