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 mimies the substrate alpha, alpha-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.
Uchida
C
C
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Yamagishi
T
T
Kitahashi
H
H
Iwaisaki
Y
Y
Ogawa
S
S
D000818:Animals; D012831:Bombyx / Q000201:enzymology; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014198:Trehalase / Q000037:antagonists & inhibitors*
D004187:Disaccharides; D004791:Enzyme Inhibitors; C071816:trehazolin; D014198:Trehalase