Discovery of N-benzyl-2-[(4S)-4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-6-yl]-N-isopropylacetamide, an orally active, gut-selective CCK1 receptor agonist for the potential treatment of obesity

We describe the design, synthesis, and structure–activity relationships of triazolobenzodiazepinone CCK1 receptor agonists. Analogs in this series demonstrate potent agonist activity as measured by in vitro and in vivo assays for CCK1 agonism. Our efforts resulted in the identification of compound 4a which significantly reduced food intake with minimal systemic exposure in rodents.

Graphical abstractWe report the design, synthesis, and SAR of triazolobenzodiazepinone CCK1 receptor agonists. Compound 4a is a potent, selective CCK1 receptor agonist which reduces food intake in rodents with minimal systemic exposure.Figure optionsDownload full-size imageDownload as PowerPoint slide