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

Abstract

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, 1 l-(1,2,4, 5 3 )-5-amino -1-C- (hydroxymethyl)-1,2,3,4-cyclopentanetetraol l-4 and its N-phenyl cyclic isourea derivative S-19 were shown to have strong inhibitory activity, IC 50 4 × 10 −7 and 7.6 × 10 −9 M, respectively, against baker's 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.