Document Report Card

ID: ALA1156817

Journal: J Med Chem

Title: Fructose-1,6-bisphosphatase Inhibitors. 2. Design, synthesis, and structure-activity relationship of a series of phosphonic acid containing benzimidazoles that function as 5'-adenosinemonophosphate (AMP) mimics.

Authors: Dang Q, Kasibhatla SR, Xiao W, Liu Y, Dare J, Taplin F, Reddy KR, Scarlato GR, Gibson T, van Poelje PD, Potter SC, Erion MD.

Abstract: Efforts to enhance the inhibitory potency of the initial purine series of fructose-1,6-bisphosphatase (FBPase) inhibitors led to the discovery of a series of benzimidazole analogues with human FBPase IC(50)s < 100 nM. Inhibitor 4.4 emerged as a lead compound based on its potent inhibition of human liver FBPase (IC(50) = 55 nM) and significant glucose lowering in normal fasted rats. Intravenous administration of 4.4 to Zucker diabetic fatty rats led to rapid and robust glucose lowering, thereby providing the first evidence that FBPase inhibitors could improve glycemia in animal models of type 2 diabetes.

CiteXplore: 20055427

DOI: 10.1021/jm901420x