α-Glucopyranoimidazolines as intermediate analogue inhibitors of family 20 β-N-acetylglucosaminidases Original Research Article

The α-glucopyranoimidazolines, 2-methyl-(1,2-dideoxy-α-d-glucopyrano)[2,1-d]-1-imidazolines 1 and 2, have been synthesized and evaluated as inhibitors of β-N-acetylglucosaminidases (NAGs). Compounds 1 and 2, mimicking the oxazolinium ion intermediate in enzyme catalysis, served as potent and competitive inhibitors of family 20 NAGs with Ki as low as 0.1 μM, but showed no inhibitory activities toward family 3 NAGs. Due to structural and electrostatic resemblance to the oxazolinium ion intermediate, the α-glucopyranoimidazolines may lead to novel and selective inhibitors of mechanistically related glycosidases such as family 18 chitinases.