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A series of novel indole derivatives was designed and synthesized as inhibitors of fructose-1,6-bisphosphatase (FBPase). The most potent compound 14c was identified with an IC 50 value of 0.10 μM by testing the inhibitory activity against recombinant human FBPase. The structure-activity relationships were investigated on the substitution at 4- and 5-position of the indole scaffold. The binding interactions of the title compounds at AMP binding site of FBPase were predicted using CDOCKER algorithm. [ABSTRACT FROM AUTHOR]

Abstract: A series of novel indole derivatives was synthesized as inhibitors of fructose-1,6-bisphosphatase (FBPase). Extensive structure–activity relationships were conducted and led to a potent FBPase inhibitor 3.9 with an IC50 of 0.99μM. The binding mode of this series of indoles was predicted using CDOCKER algorithm. The results of this research will shed light on the further design and optimization of novel small molecules as FBPase inhibitors. [Copyright &y& Elsevier]