Further chemical modification of trehalase inhibitor trehazolin: Structure and inhibitory-activity relationship of the inhibitor

Eight analogues of trehazolin were synthesized and tested for trehalase inhibitors. Deoxygenation of the cyclopentanepolyol moiety all decreased the inhibitory activity. Epimerization at the branching point of the cyclopentane ring did not so affect the potency. The cyclic isourea part was shown to be replaced with guanidine structure with a considerable decrease of activity. The 6′-fluoro-6′-deoxy derivative was still a strong inhibitor. It seems that trehazolin strictly mimics the substrate ,-trehalose and any structural change and/or removal of the hydroxyl functions appreciably influence its potency. The present results led to finding 5-aminocyclopentane-1,2,3,4-tetraols to be new lead compounds for glycohydrolase inhibitors.