Orally active aminopyridines as inhibitors of tetrameric fructose-1,6-bisphosphatase

A novel sulfonylureido pyridine series exemplified by compound 19 yielded potent inhibitors of FBPase showing significant glucose reduction and modest glycogen lowering in the acute db/db mouse model for Type-2 diabetes. Our inhibitors occupy the allosteric binding site and also extend into the dyad interface region of tetrameric FBPase.

Graphical abstractCompound 19 is representative of a novel sulfonylureido pyridine series that yielded potent inhibitors of fructose-1,6-bisphosphatase, showing significant glucose reduction and modest glycogen lowering in the acute db/db mouse model for Type-2 diabetes.Figure optionsDownload full-size imageDownload as PowerPoint slide