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Chembiochem : a European journal of chemical biology

A novel competitive class of α-glucosidase inhibitors: (E)-1-phenyl-3-(4-styrylphenyl)urea derivatives.


PMID 20827790

Abstract

Competitive glycosidase inhibitors are generally sugar mimics that are costly and tedious to obtain because they require challenging and elongated chemical synthesis, which must be stereo- and regiocontrolled. Here, we show that readily accessible achiral (E)-1-phenyl-3-(4-strylphenyl)ureas are potent competitive α-glucosidase inhibitors. A systematic synthesis study shows that the 1-phenyl moiety on the urea is critical for ensuring competitive inhibition, and substituents on both terminal phenyl groups contribute to inhibition potency. The most potent inhibitor, compound 12 (IC(50)=8.4 μM, K(i)=3.2 μM), manifested a simple slow-binding inhibition profile for α-glucosidase with the kinetic parameters k(3)=0.005256 μM(-1) min(-1), k(4)=0.003024 min(-1), and K(i)(app) =0.5753 μM.