Synthesis and biological evaluation of potent glycosidase inhibitors: N-phenyl cyclic isourea derivatives of 5-amino- and 5-amino-C-(hydroxymethyl)-1,2,3,4-cyclopentanetetraols Original Research Article

Twenty-four stereoisomers of 5-amino- and 5-amino-C-(hydroxymethyl)-1,2,3,4-cyclopentanetetraols and twenty-six of the corresponding N-phenyl cyclic isourea derivatives were assayed for inhibitory activity against six glycosidases. Among them, as has been expected for structure mimics of putative transition state glucopyranosyl cation for glycoside hydrolysis, 1l-(1,2,4,53)-5-amino-1-C-(hydroxymethyl)-1,2,3,4-cyclopentanetetraoll-4 and its N-phenyl cyclic isourea derivative S-19 were shown to have strong inhibitory activity, IC50 4 × 10−7 and 7.6 × 10−9 M, respectively, against bakerʹs yeast α-glucosidase. It has been analogously explained that compounds R,S-22 and R,S-26 possessed high inhibitory potency against Escherichia coli and bovine liver β-galactosidases, respectively.