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A Novel Competitive Class of α‐Glucosidase Inhibitors: ( E )‐1‐Phenyl‐3‐(4‐Styrylphenyl)Urea Derivatives
Author(s) -
Kim Jun Young,
Lee Ji Won,
Kim Young Soo,
Lee Yuno,
Ryu Young Bae,
Kim Songmi,
Ryu Hyung Won,
CurtisLong Marcus J.,
Lee Keun Woo,
Lee Woo Song,
Park Ki Hun
Publication year - 2010
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201000376
Subject(s) - moiety , chemistry , urea , stereochemistry , potency , combinatorial chemistry , in vitro , organic chemistry , biochemistry
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 μ M , K i =3.2 μ M ), manifested a simple slow‐binding inhibition profile for α‐glucosidase with the kinetic parameters k 3 =0.005256 μ M −1 min −1 , k 4 =0.003024 min −1 , and ${K{{{\rm app}\hfill \atop {\rm i}\hfill}}}$ =0.5753 μ M .